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Primary vitreoretinal lymphoma (PVRL) is a rare form of primary central nervous system (CNS) lymphoma (PCNSL) arising in the intraocular compartment without brain involvement. Despite its apparent indolent clinical course, PVRL can cause permanent vision loss and CNS relapse, the major cause of death in patients with PVRL. The pathophysiology of PVRL is unknown. As in PCNSL, the transformation of the tumor cells likely originates outside the CNS, before the cells migrate to the eye and proliferate within an immune-permissive microenvironment. PVRL exhibits a biased immunoglobulin repertoire, suggesting underlying antigen selection. The diagnosis remains challenging, requiring close coordination between ophthalmologists and cytologists. Because of their rarity and fragility in the vitreous, lymphoma cells cannot always be identified. Interleukin levels, molecular biology, and imaging are used in combination with clinical ophthalmological examination to support the diagnosis of PVRL. Multi-institutional prospective studies are urgently needed to validate the equivocal conclusions regarding treatments drawn from heterogeneous retrospective or small cohort studies. Intravitreal injection of methotrexate or rituximab or local radiotherapy is effective at clearing tumor cells within the eyes but does not prevent CNS relapse. Systemic treatment based on high-dose methotrexate chemotherapy, with or without local treatment, might reduce this risk. At relapse, intensive consolidation chemotherapy followed by stem cell transplantation can be considered. Single-agent ibrutinib, lenalidomide, and temozolomide treatments are effective in patients with relapsed PVRL and should be tested as first-line treatments. Therapeutic response assessment based on clinical examination is improved by measuring cytokine levels but still needs to be refined.

Next-generation sequencing (NGS) has been applied to measurable/minimal residual disease (MRD) monitoring after induction chemotherapy in patients with acute myeloid leukemia (AML), but the optimal time point for the test remains unclear. In this study, we aimed to investigate the clinical significance of NGS MRD at 2 different time points. We performed targeted NGS of 54 genes in bone marrow cells serially obtained at diagnosis, first complete remission (first time point), and after the first consolidation chemotherapy (second time point) from 335 de novo AML patients. Excluding DNMT3A, TET2, and ASXL1 mutations, which are commonly present in individuals with clonal hematopoiesis of indeterminate potential, MRD could be detected in 46.4% of patients at the first time point (MRD1st), and 28.9% at the second time point (MRD2nd). The patients with detectable NGS MRD at either time point had a significantly higher cumulative incidence of relapse and shorter relapse-free survival and overall survival. In multivariate analysis, MRD1st and MRD2nd were both independent poor prognostic factors. However, the patients with positive MRD1st but negative MRD2nd had a similar good prognosis as those with negative MRD at both time points. The incorporation of multiparameter flow cytometry and NGS MRD revealed that the presence of NGS MRD predicted poorer prognosis among the patients without detectable MRD by multiparameter flow cytometry at the second time point but not the first time point. In conclusion, the presence of NGS MRD, especially after the first consolidation therapy, can help predict the clinical outcome of AML patients.

Introduction The Australasian Leukaemia and Lymphoma Group (ALLG) conducted a randomized trial (AMLM16) combining the FLT3 inhibitor sorafenib (SOR) or placebo (PBO) with intensive induction and consolidation chemotherapy, followed by 12 months of maintenance therapy in patients with FLT3-ITD mutant AML. The clinical results of the AMLM16 study are detailed in a companion abstract co-submitted to ASH 2020. We hypothesized that the optimal time to administer sorafenib would be d4-10 of induction in order to limit overlap with anthracyclines on d1-3 and to avoid high FLT3 ligand (FLT3L) levels beyond d10, which could abrogate FLT3 on-target activity and diminish the therapeutic index. Key objectives of the correlative studies were to correlate in vivo SOR activity on suppression of FLT3 phosphorylation (P-FLT3) using the plasma inhibitory assay (PIA) with relapse risk and to assess for the presence of FLT3-ITD measurable residual disease (MRD) after therapy. Methods Patients aged 18-65 years with newly diagnosed AML (excluding APML) were enrolled to a National Blood Cancer Registry; those with a FLT3-ITD mutant: wild-type allelic ratio (AR) ≥ 0.05 were eligible for enrolment to the AMLM16 study. Patients were randomized 2:1 to SOR or PBO 400mg orally bd on d4-10 of induction and each consolidation cycle in combination with intensive chemotherapy and for 12 months as maintenance monotherapy. Serum FLT3-L levels were measured by ELISA, SOR and its metabolites by mass spectrometry. SOR mediated inhibition of FLT3 was measured in serum samples using the PIA as previously described (Levis, Blood 2006) in which P-FLT3 inhibition to ≤15% baseline is defined as response. Quantitation of FLT3-ITD levels by NGS was performed at study screening and after each induction and consolidation chemotherapy cycle. Quantitation was by amplicon-based sequencing which detected ITDs >6 bp with a sensitivity of 0.001%: levels below and above this were termed measurable residual disease (MRD) negative and positive respectively. Prepared libraries were sequenced (Illumina) using 150 bp paired-end reads with a minimum coverage of 400,000 reads. Bioinformatics analysis was performed using getITD (Blätte, Leukemia, 2019). Results 98 evaluable patients were randomized to induction with either SOR (n=65) or PBO (n=33) with a FLT3-ITD AR ranging from 0.05 to 8.4. FLT3-ITD AR was ≥ 0.5 or ≥ 0.7 in 48% and 29%, respectively. During induction, FLT3-L levels increased by an average of 150-fold from d4 to d10 and a further 1.6-fold to d15, with a return to baseline by d28. Serial plasma samples to assess PIA were available for 63 patients (Fig A). Response to ≤15% on d10 (relative to d4) was observed in 88% of SOR patients, compared with 4.5% receiving PBO. The relapse risk was 32% and 62% among PIA responders and non-responders, respectively (Fig A). Among patients with PIA response to ≤15% by d10 (the last day of SOR/PBO), only 8.3% had evidence of a sustained PIA response by d15. Reduction of FLT3-ITD to undetectable levels (VAF We compared the relationship between inhibition of P-FLT3 on d10 and bone marrow FLT3-ITD MRD after induction with relapse risk (Fig D, E). In the SOR arm, if P-FLT3 was not reduced to ≤15%, all patients had persistent FLT3-ITD MRD after induction and the relapse risk was 80% (Fig D). In contrast, if P-FLT3 inhibition was ≤15% and FLT3-ITD MRD not detected, the relapse risk was only 20%. In the PBO arm after induction, persistent and undetectable FLT3-ITD MRD (VAF Conclusions These studies demonstrate that in vivo SOR inhibited P-FLT3 to ≤15% during induction in the majority of cases and was associated with reduced relapse risk. Persistent FLT3-ITD MRD post-induction was associated with a high relapse risk in both treatment arms. For patients receiving SOR, failure to reduce P-FLT3 response to ≤15% was associated with a high risk of persistent FLT3-ITD MRD and clinical relapse. Disclosures Anstee: Walter and Eliza Hall Institute: Patents & Royalties: milestone and royalty payments related to venetoclax.. Levis:Menarini: Honoraria; Amgen: Honoraria; FujiFilm: Honoraria, Research Funding; Daiichi-Sankyo: Honoraria; Astellas: Honoraria, Research Funding. Enjeti:Novartis: Membership on an entity's Board of Directors or advisory committees; Astellas: Membership on an entity's Board of Directors or advisory committees; Alexion: Speakers Bureau; AbbVie: Membership on an entity's Board of Directors or advisory committees; Bayer: Speakers Bureau; Sanofi: Speakers Bureau. D'Rozario:Abbvie: Membership on an entity's Board of Directors or advisory committees; BMS/ Celgene: Membership on an entity's Board of Directors or advisory committees. Marlton:AbbVie: Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees; F. Hoffmann-La Roche Ltd: Membership on an entity's Board of Directors or advisory committees; Astra-Zeneca: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees; Astellas: Membership on an entity's Board of Directors or advisory committees. Roberts:Janssen: Research Funding; Servier: Research Funding; AbbVie: Research Funding; Genentech: Patents & Royalties: for venetoclax to one of my employers (Walter & Eliza Hall Institute); I receive a share of these royalties. Wei:Astra Zeneca: Honoraria, Research Funding; Novartis: Honoraria, Research Funding, Speakers Bureau; Abbvie: Honoraria, Research Funding, Speakers Bureau; Walter and Eliza Hall Institute of Medical Research: Patents & Royalties: AW is eligible for royalty payments related to venetoclax; Roche: Honoraria; Macrogenics: Honoraria; Servier: Consultancy, Honoraria, Research Funding; Amgen: Honoraria, Research Funding; Pfizer: Honoraria; Bristol Myers Squibb: Honoraria, Research Funding, Speakers Bureau; Janssen: Honoraria. OffLabel Disclosure: Sorafenib for FLT3-ITD AML

Until recently, treatment options for patients with acute myeloid leukemia (AML) were limited to cytotoxic chemotherapeutic agents that possessed little specificity for the cytogenetic and molecular mutations known to risk stratify patients with this disease. With the approval of multiple new therapies, not only have the agents that we treat patients with changed, but the way we talk about these options, decide on, and manage therapy has also been transformed. Given these complexities, it is important that we help patients make an informed decision by weighing the risk of relapse with patient wishes and desired quality of life. Shared decision making (SDM) is an approach to medical decision making for those situations in which most clinicians would agree that there is more than 1 correct choice for a patient. Here we review the principles of SDM and provide an overview of the 3-talk model and how it may be incorporated into the care of patients with AML.

Prior to novel targeted agents for chronic lymphocytic leukemia (CLL), the best chemoimmunotherapy regimen in patients with non-del(11q) disease was unclear. The role of lenalidomide was also not defined. This phase 2 study randomized 342 untreated patients with non-del(11q) CLL requiring therapy to fludarabine plus rituximab (FR; n = 123), FR plus lenalidomide consolidation (FR+L; n = 109), or FR plus cyclophosphamide (FCR; n = 110) and compared 2-year progression-free survival (PFS) rates of each to the historical control rate with FC (60%). Patients with del(11q) in at least 20% of pretreatment cells continued with FCR (n = 27) or were reassigned to FCR+L (n = 31) and excluded from the primary analysis. Among non-del(11q) patients, 2-year PFS rates were 64% (90% confidence interval [CI], 57-71; FR), 72% (90% CI, 65-79; FR+L), and 74% (90% CI, 66-80; FCR); FR+L and FCR had rates significantly greater than historical control. Median PFS was significantly shorter with FR compared with FR+L (P = .04) and FCR (P < .001): 43 (95% CI, 33-50), 61 (95% CI, 45-71), and 97 (95% CI, 61 to not reached) months, respectively. Median follow-up was 73 months and median overall survival (OS) was only reached with FCR (101 months; 95% CI, 96 to not reached). With FR+L, the risk of death decreased over time and was lower than with FR at later time points (P = .01), but not significantly different from FCR (P = .21). Future studies incorporating short courses of lenalidomide into other novel treatment regimens are justified.

First-line therapy for younger patients with peripheral T-cell non-Hodgkin lymphoma (T-NHL) consists of 6 courses of cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) with or without etoposide (CHOEP), consolidated by high-dose therapy and autologous stem cell transplantation (auto-SCT). We hypothesized that allogeneic stem cell transplantation (allo-SCT) could improve outcomes. 104 patients with peripheral T-cell non-Hodgkin lymphoma, except ALK+ anaplastic large cell lymphoma, 18 to 60 years, all stages, and all age adjusted International Prognostic Index scores, except 0 and stage I, were randomized to 4 cycles of CHOEP and 1 cycle of dexamethasone, cytosine-arabinoside, and platinum (DHAP) followed by high-dose therapy and auto-SCT or myeloablative conditioning and allo-SCT. The primary end point was event-free survival (EFS) at 3 years. After a median follow-up of 42 months, the 3-year EFS after allo-SCT was 43%, as compared with 38% after auto-SCT. Overall survival at 3 years was 57% vs 70% after allo- or auto-SCT, without significant differences between treatment arms. None of the 21 responding patients proceeding to allo-SCT relapsed, as opposed to 13 of 36 patients (36%) proceeding to auto-SCT. Eight of 26 patients (31%) and none of 41 patients died of transplant-related toxicity after allo- and auto-SCT, respectively. The strong graft-versus-lymphoma effect after allo-SCT was counterbalanced by transplant-related mortality. This trial is registered at www.clinicaltrials.gov as #NCT00984412.

Background: Ivosidenib (IVO) and enasidenib (ENA) are oral inhibitors of mutant IDH1 (mIDH1) and mutant IDH2 (mIDH2), respectively, FDA-approved for the treatment of relapsed/refractory IDH-mutant acute myeloid leukemia (AML). Here we report updated response and survival results from a phase 1 study of these agents when combined with intensive chemotherapy in patients with newly diagnosed m IDH1/2 AML. Methods: The design of this open-label, multicenter, phase 1 study (NCT02632708) has been previously described. Briefly, eligible patients with newly diagnosed m IDH1 or m IDH2 AML were treated with induction therapy (daunorubicin 60 mg/m 2/day or idarubicin 12 mg/m 2/day × 3 days with cytarabine 200 mg/m 2/day × 7 days) in combination with either IVO 500 mg once daily (for m IDH1) or ENA 100 mg once daily (for m IDH2). After induction, patients received up to 4 cycles of consolidation therapy while continuing the mIDH inhibitor. Patients who completed or were ineligible for consolidation continued on maintenance IVO or ENA until the end of the study. IDH mutation clearance and measurable residual disease (MRD) negativity were assessed using BEAMing digital PCR and multiparameter flow cytometry (Stein et al. Blood 2021). Results: As of 16-Jan-2020, 153 patients had been treated: 60 in the IVO cohort (median age 62.5 years, range 24-76) and 93 in the ENA cohort (median age 63.0 years, range 27-77); 2 patients assigned to start ENA on Day 8 had an ongoing adverse event or died on Day 8, and therefore never received ENA and were not included in the efficacy analysis. Secondary AML (sAML; arising after an antecedent hematologic disorder, or after exposure to genotoxic injury) was present in 18/60 (30.0%) IVO-treated patients and in 35/93 (37.6%) ENA-treated patients. In patients with sAML, 4 (22.2%) and 17 (48.6%) IVO-treated and ENA-treated patients, respectively, had previously received a hypomethylating agent. IVO or ENA combined with induction and consolidation were well tolerated (Stein et al . Blood 2021). Among the 60 IVO-treated patients, a response of complete remission (CR), CR with incomplete hematologic recovery (CRi), or CR with incomplete platelet recovery (CRp) was achieved in 37/42 (88.1%) patients with de novo AML and in 10/18 (55.6%) patients with sAML. Among the 91 ENA-treated patients, a response of CR, CRi, or CRp was achieved in 45/56 (80.4%) patients with de novo AML and in 22/35 (62.9%) patients with sAML. Best overall response is reported in Table 1. Patients achieving CR, CRi, or CRp who had available samples were analyzed for IDH mutation clearance and MRD negativity. In those treated with IVO, the IDH1 mutation was cleared in 16/41 (39.0%) patients, and 16/20 (80.0%) were considered MRD negative. In those treated with ENA, the IDH2 mutation was cleared in 15/64 (23.4%) patients, and 10/16 (62.5%) were MRD negative (Stein et al . Blood 2021). Thirty-five (58.3%) IVO-treated patients received ≥1 cycle of consolidation therapy, 18 (30.0%) patients received maintenance after consolidation, 1 (1.7%) patient received maintenance after induction, and 29 (48.3%) patients proceeded to hematopoietic stem cell transplantation (HSCT). Forty-six (49.5%) ENA-treated patients received ≥1 cycle of consolidation therapy, 17 (18.3%) patients received maintenance after consolidation, 7 (7.5%) patients entered maintenance without consolidation, and 43 (46.2%) patients proceeded to HSCT. Median durations of follow-up were 21.2 and 23.7 months for IVO and ENA, respectively. For patients who entered maintenance, median duration of active maintenance was 13.8 and 11.0 months for IVO and ENA, respectively. Of patients who achieved CR, 7/42 (16.7%) of those treated with IVO and 7/51 (13.7%) of those treated with ENA experienced relapse or death. Overall survival is reported in Figure 1. Updated data from July 2021 will be presented. Conclusion: IVO or ENA in combination with induction and consolidation therapy have shown acceptable safety profiles, with ≥80% CR+CRi/CRp remission rates in patients with m IDH de novo AML. With over 21 months of follow-up, overall survival rates were high, with 12-month survival probabilities of >75% for both the IVO- and ENA-treated patients. The clinical benefit of adding IVO or ENA to induction, consolidation, and maintenance therapy for patients with newly diagnosed m IDH AML is being further evaluated in the ongoing HOVON150AML randomized phase 3 trial (NCT03839771). Figure 1 Figure 1. Disclosures Stein: Jazz Pharmaceuticals: Consultancy; Foghorn Therapeutics: Consultancy; Blueprint Medicines: Consultancy; Gilead Sciences, Inc.: Consultancy; Abbvie: Consultancy; Janssen Pharmaceuticals: Consultancy; Genentech: Consultancy; Bristol Myers Squibb: Consultancy; Celgene: Consultancy; Novartis: Consultancy; Astellas: Consultancy; Syndax Pharmaceuticals: Consultancy; Syros Pharmaceuticals, Inc.: Consultancy; Agios Pharmaceuticals, Inc: Consultancy; PinotBio: Consultancy; Daiichi Sankyo: Consultancy. DiNardo: Takeda: Honoraria; Novartis: Honoraria; AbbVie: Consultancy, Research Funding; Agios/Servier: Consultancy, Honoraria, Research Funding; Foghorn: Honoraria, Research Funding; Celgene, a Bristol Myers Squibb company: Honoraria, Research Funding; GlaxoSmithKline: Membership on an entity's Board of Directors or advisory committees; Bristol Myers Squibb: Honoraria, Research Funding; ImmuneOnc: Honoraria, Research Funding; Notable Labs: Current holder of stock options in a privately-held company, Membership on an entity's Board of Directors or advisory committees; Forma: Honoraria, Research Funding. Fathi: Kite: Consultancy, Honoraria; Foghorn: Consultancy, Honoraria; Kura: Consultancy, Honoraria; Trillium: Consultancy, Honoraria; Genentech: Consultancy, Honoraria; Daiichi Sankyo: Consultancy, Honoraria; Astellas: Consultancy, Honoraria; Seattle Genetics: Consultancy, Honoraria; Blueprint: Consultancy, Honoraria; Pfizer: Consultancy, Honoraria; Takeda: Consultancy, Honoraria; Celgene/BMS: Consultancy, Honoraria, Research Funding; Servier: Research Funding; Agios: Consultancy, Honoraria, Research Funding; AbbVie: Consultancy, Honoraria, Research Funding; Morphosys: Consultancy, Honoraria; Ipsen: Consultancy, Honoraria. Mims: Syndax Pharmaceuticals: Consultancy; Abbvie: Consultancy; Genentech: Consultancy; Kura Oncology: Consultancy; Leukemia and Lymphoma Society: Consultancy; BMS: Consultancy; Jazz Pharmaceuticals: Consultancy; Aptevo: Research Funding; Glycomemetics: Research Funding; Xencor: Research Funding; Daiichi-Saynko: Consultancy. Savona: Karyopharm: Consultancy, Current equity holder in publicly-traded company, Membership on an entity's Board of Directors or advisory committees; Geron: Consultancy, Membership on an entity's Board of Directors or advisory committees; CTI: Consultancy, Membership on an entity's Board of Directors or advisory committees; BMS-Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees; NOVARTIS: Consultancy, Membership on an entity's Board of Directors or advisory committees; Ryvu: Consultancy, Membership on an entity's Board of Directors or advisory committees; Sierra Oncology: Consultancy, Membership on an entity's Board of Directors or advisory committees; Taiho: Consultancy, Membership on an entity's Board of Directors or advisory committees; TG Therapeutics: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Takeda: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; ALX Oncology: Research Funding; Astex: Research Funding; Incyte: Research Funding. Stein: Amgen: Consultancy, Speakers Bureau; Celgene: Speakers Bureau; Stemline: Speakers Bureau. Stone: Boston Pharmaceuticals: Consultancy; Elevate Bio: Membership on an entity's Board of Directors or advisory committees; BerGen Bio: Membership on an entity's Board of Directors or advisory committees; Innate: Consultancy; Janssen: Consultancy; Jazz: Consultancy; Bristol Myers Squibb: Consultancy; Novartis: Consultancy, Research Funding; Onconova: Consultancy; Syndax: Membership on an entity's Board of Directors or advisory committees; Syntrix/ACI: Membership on an entity's Board of Directors or advisory committees; Syros: Membership on an entity's Board of Directors or advisory committees; Foghorn Therapeutics: Consultancy; Astellas: Membership on an entity's Board of Directors or advisory committees; AbbVie: Consultancy; Arog: Consultancy, Research Funding; Gemoab: Membership on an entity's Board of Directors or advisory committees; GlaxoSmithKline: Consultancy; Aprea: Consultancy; Amgen: Membership on an entity's Board of Directors or advisory committees; Actinium: Membership on an entity's Board of Directors or advisory committees; Takeda: Consultancy; Agios: Consultancy, Research Funding; Celgene: Consultancy; Macrogenics: Consultancy. Winer: Abbvie: Consultancy; Takeda: Consultancy; Novartis: Consultancy. Döhner: AstraZeneca: Consultancy, Honoraria; Astex: Consultancy, Honoraria; Astellas: Consultancy, Honoraria, Research Funding; Amgen: Consultancy, Honoraria, Research Funding; Celgene: Consultancy, Honoraria, Research Funding; Berlin-Chemie: Consultancy, Honoraria; Bristol Myers Squibb: Consultancy, Honoraria, Research Funding; Agios: Consultancy, Honoraria, Research Funding; Jazz: Consultancy, Honoraria, Research Funding; Gilead: Consultancy, Honoraria; Pfizer: Research Funding; Ulm University Hospital: Current Employment; Roche: Consultancy, Honoraria; Abbvie: Consultancy, Honoraria, Research Funding; GEMoaB: Consultancy, Honoraria; Helsinn: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; Novartis: Consultancy, Honoraria, Research Funding; Oxford Biomedicals: Consultancy, Honoraria. Pollyea: Syndax: Honoraria; Takeda: Honoraria; Astellas: Honoraria; Karyopharm: Consultancy, Honoraria; Foghorn: Honoraria; Kiadis: Honoraria; Syros: Consultancy, Honoraria; Novartis: Consultancy, Honoraria; Teva: Research Funding; Amgen: Honoraria; Aprea: Honoraria; Jazz: Honoraria; Gilead: Consultancy, Honoraria; Genentech: Consultancy, Honoraria; Celgene: Honoraria; Bristol Myers Squibb: Honoraria; AbbVie: Consultancy, Honoraria, Research Funding. McCloskey: Jazz: Consultancy, Speakers Bureau; Takeda: Consultancy, Speakers Bureau; Pfizer: Consultancy; Novartis: Consultancy; Amgen: Speakers Bureau; Incyte: Speakers Bureau; COTA: Other: Equity Ownership; BMS: Honoraria, Speakers Bureau. Odenike: AbbVie, Celgene, Impact Biomedicines, Novartis, Taiho Oncology, Takeda: Consultancy; Celgene, Incyte, AstraZeneca, Astex, NS Pharma, AbbVie, Gilead, Janssen, Oncotherapy, Agios, CTI/Baxalta, Aprea: Research Funding. Ossenkoppele: Agios: Consultancy, Honoraria; BMS/Celgene: Consultancy, Honoraria; Jazz: Consultancy, Honoraria; Servier: Consultancy, Honoraria; Abbvie, AGIOS, BMS/Celgene Astellas,AMGEN, Gilead,Servier,JAZZ,Servier Novartis: Consultancy, Honoraria; Gilead: Consultancy, Honoraria; Astellas: Consultancy, Honoraria. Patel: Aptevo Therapeutics: Research Funding; BMS-Celgene, Agios: Membership on an entity's Board of Directors or advisory committees; Peerview: Honoraria. Roshal: Celgene: Other: Provision of services; Auron Therapeutics: Other: Ownership / Equity interests; Provision of services; Physicians' Education Resource: Other: Provision of services. Frattini: Celgene/BMS: Current equity holder in publicly-traded company, Ended employment in the past 24 months; Cellectis, Inc.: Current Employment, Current equity holder in publicly-traded company. Lersch: Celgene, a Bristol-Myers Squibb Company: Current Employment. Nabhan: Agios: Divested equity in a private or publicly-traded company in the past 24 months, Ended employment in the past 24 months. Almon: Agios: Divested equity in a private or publicly-traded company in the past 24 months, Ended employment in the past 24 months. Saatcioglu: Servier Pharmaceuticals: Current Employment. Zhang: Servier: Current Employment; Agios: Current equity holder in publicly-traded company, Ended employment in the past 24 months. Cooper: Agios: Divested equity in a private or publicly-traded company in the past 24 months, Ended employment in the past 24 months; Servier: Current Employment. Kantarjian: Pfizer: Honoraria, Research Funding; Daiichi-Sankyo: Research Funding; AbbVie: Honoraria, Research Funding; Aptitude Health: Honoraria; Ipsen Pharmaceuticals: Honoraria; Astellas Health: Honoraria; Amgen: Honoraria, Research Funding; Ascentage: Research Funding; BMS: Research Funding; Astra Zeneca: Honoraria; Novartis: Honoraria, Research Funding; Jazz: Research Funding; Immunogen: Research Funding; KAHR Medical Ltd: Honoraria; NOVA Research: Honoraria; Precision Biosciences: Honoraria; Taiho Pharmaceutical Canada: Honoraria. Tallman: Kura: Membership on an entity's Board of Directors or advisory committees; Syros: Membership on an entity's Board of Directors or advisory committees; NYU Grand Rounds: Honoraria; Innate Pharma: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees; Biosight: Membership on an entity's Board of Directors or advisory committees; Roche: Membership on an entity's Board of Directors or advisory committees; Jazz Pharma: Membership on an entity's Board of Directors or advisory committees; Oncolyze: Membership on an entity's Board of Directors or advisory committees; KAHR: Membership on an entity's Board of Directors or advisory committees; Orsenix: Membership on an entity's Board of Directors or advisory committees; Daiichi-Sankyo: Membership on an entity's Board of Directors or advisory committees; Abbvie: Membership on an entity's Board of Directors or advisory committees; Amgen: Research Funding; Rafael Pharmaceuticals: Research Funding; Glycomimetics: Research Funding; Biosight: Research Funding; Orsenix: Research Funding; Abbvie: Research Funding; Mayo Clinic: Honoraria; UC DAVIS: Honoraria; Northwell Grand Rounds: Honoraria; NYU Grand Rounds: Honoraria; Danbury Hospital Tumor Board: Honoraria; Acute Leukemia Forum: Honoraria; Miami Leukemia Symposium: Honoraria; New Orleans Cancer Symposium: Honoraria; ASH: Honoraria; NCCN: Honoraria. OffLabel Disclosure: Ivosidenib and enasidenib are indicated for the treatment of adult patients with relapsed or refractory AML with a susceptible IDH1 mutation (ivosidenib) or an IDH2 mutation (enasidenib) as detected by an FDA-approved test. Enasidenib and ivosidenib are investigational products in tumors other than relapsed/refractory AML.

Background High-dose melphalan (HDM) at 200 mg/m2 is a myeloablative consolidation treatment prior to autologous stem cell transplantation (ASCT) in patients with multiple myeloma (MM) and is administered in 1-day or divided over 2-days. Although the 1-day regimen (lower AUC) has been shown to result in significantly less gastro-intestinal toxicity, it is not completely clear whether this administration strategy has any deleterious effects on efficacy, compared to the 2-day regimen. In this retrospective cohort study, we aimed to evaluate the effects of 1- or 2-day dosing of HDM on disease remission, progression-free survival (PFS) and overall survival (OS) in patients with MM. Methods Data from two academic centers in Amsterdam that have recently merged were used for the analysis, with one of the centers using the 1-day regimen and the other the 2-days regimen. A total of 265 patients with MM divided over the 1-day group (n=174) and 2-day group (n=91) treated between July 2017 and February 2020, were included in the study. The primary endpoint was the proportion of patients with at least very good partial remission (≥VGPR) at day ±90 post-ASCT. Secondary endpoints were overall survival (OS), progression-free survival (PFS), duration of hospitalization post-ASCT, engraftment period of neutrophils and platelets, and complications (other than mucositis) during hospitalization. Results Patient characteristics are summarized in Table 1. Remission status of ≥VGPR was comparable between the 1-day and 2-day groups (84% vs. 80% respectively). After a median follow-up of 21 months, OS (92% vs. 91%) and PFS (80% vs. 81%) were comparable in the 1-day and 2-day group respectively. There were no differences in the incidence of hematologic adverse events between the 1-day and 2-day groups (neutropenia; 98% vs. 100%, thrombocytopenia; 90% vs. 96% respectively). Median time to neutrophil engraftment (ANC >0.5 x10 9 L -1) was significantly shorter in the 2-day group than in the 1-day group (14 days vs. 18 days, p = 0.002). Median time to platelet engraftment (platelets >20 x10 9 L -1) was comparable between the groups. Lower CD34+ cell counts were administered in the 1-day group compared to the 2-day group (2.6 vs. 3.4 x10 6/kg, p Conclusion The use of 1-day HDM as consolidation treatment in MM patients resulted in equal disease response, progression-free survival and overall survival as compared to 2-day HDM. Based on the results of this study showing comparable efficacy and earlier findings of reduced toxicity with the 1-day HDM administration, we recommend the 1-day protocol for HDM. Interestingly, our results also confirmed that patients might benefit from higher counts of reinfused CD34+/enucleated cells. Figure 1 Figure 1. Disclosures Wondergem: Novartis: Honoraria. de Leeuw: Takeda: Membership on an entity's Board of Directors or advisory committees. Biemond: Sanquin: Research Funding; Celgene: Honoraria; CSL Behring: Honoraria; Novo Nordisk: Honoraria; Novartis: Honoraria, Research Funding, Speakers Bureau; Global Blood Therapeutics: Honoraria, Research Funding, Speakers Bureau. van de Donk: Janssen Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees, Research Funding; Amgen: Membership on an entity's Board of Directors or advisory committees, Research Funding; Takeda: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding; Adaptive Biotechnologies: Membership on an entity's Board of Directors or advisory committees; Bristol Myers Squibb: Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Membership on an entity's Board of Directors or advisory committees; Roche: Membership on an entity's Board of Directors or advisory committees; Bayer: Membership on an entity's Board of Directors or advisory committees; Servier: Membership on an entity's Board of Directors or advisory committees; Cellectis: Research Funding. Zweegman: Sanofi: Membership on an entity's Board of Directors or advisory committees; BMS: Membership on an entity's Board of Directors or advisory committees; Takeda: Membership on an entity's Board of Directors or advisory committees, Research Funding; Oncopeptides: Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees, Research Funding. Nur: Roche: Speakers Bureau; Celgene: Speakers Bureau; Novartis: Research Funding, Speakers Bureau.

Background: Spleen tyrosine kinase (SYK) is a component of both lymphoid and myeloid cell signaling pathways and has been implicated in the pathogenesis of a subset of acute myeloid leukemia (AML) defined by dysregulated expression of the HOXA9 and MEIS1 transcription factors. Entospletinib (ENTO) is an oral, selective SYK inhibitor that is acceptably tolerated when administered with intensive induction and consolidation in newly diagnosed AML patients. In a phase 2 study, following induction with cytarabine and daunorubicin (7+3) plus ENTO, higher rates of complete response (CR) or CR with incomplete hematologic recovery (CRi) were observed in patients with rearrangements of the KMT2A (MLL) gene (MLL-r) and mutations of the nucleophosmin 1 (NPM1) gene, both of which are associated with aberrant expression of HOXA9 and MEIS1, as compared to patients without these mutations. In an exploratory analysis, patients with HOXA9/MEIS1 expression levels above the median experienced superior overall survival (OS) as compared to patients with expression levels below the median. In the AGILITY trial, we hypothesize that the addition of ENTO to intensive induction/consolidation in newly diagnosed patients with NPM1-mutated AML will improve the rate of CR without evidence of measurable residual disease (MRD-negative CR) post-induction and duration of event-free survival (EFS). Methods: AGILITY will be a global, multi-center, double-blind, placebo-controlled trial of ENTO in combination with cytarabine plus daunorubicin or idarubicin induction (7+3) and age-adjusted high-dose cytarabine (HiDAC) consolidation in newly diagnosed AML patients aged 18-75 years who are candidates for intensive induction and harbor a documented NPM1 mutation based on local or central mutation testing. Patients with co-mutated FLT3 (internal tandem duplication or tyrosine kinase domain) and for whom midostaurin with 7+3 is indicated are excluded. Patients will be stratified based on age ( An independent data-monitoring committee will monitor emerging safety and efficacy data from this trial on an ongoing basis. Disclosures Byrd: Vincerx Pharmaceuticals: Current equity holder in publicly-traded company, Membership on an entity's Board of Directors or advisory committees; Novartis, Trillium, Astellas, AstraZeneca, Pharmacyclics, Syndax: Consultancy, Honoraria; Newave: Membership on an entity's Board of Directors or advisory committees. Cortes: Bristol Myers Squibb, Daiichi Sankyo, Jazz Pharmaceuticals, Astellas, Novartis, Pfizer, Takeda, BioPath Holdings, Incyte: Consultancy, Research Funding; Novartis: Consultancy, Research Funding; Bio-Path Holdings, Inc.: Consultancy, Membership on an entity's Board of Directors or advisory committees; Pfizer: Consultancy, Research Funding; Takeda: Consultancy, Research Funding; Sun Pharma: Consultancy, Research Funding. Minden: Astellas: Consultancy. Oellerich: Roche: Consultancy; Gilead: Research Funding; Kronos Bio, Inc.: Consultancy; Merck KGaA: Consultancy, Research Funding. Stein: Syros Pharmaceuticals, Inc.: Consultancy; Daiichi Sankyo: Consultancy; PinotBio: Consultancy; Celgene: Consultancy; Bristol Myers Squibb: Consultancy; Jazz Pharmaceuticals: Consultancy; Foghorn Therapeutics: Consultancy; Blueprint Medicines: Consultancy; Gilead Sciences, Inc.: Consultancy; Abbvie: Consultancy; Janssen Pharmaceuticals: Consultancy; Genentech: Consultancy; Syndax Pharmaceuticals: Consultancy; Agios Pharmaceuticals, Inc: Consultancy; Novartis: Consultancy; Astellas: Consultancy. Elder: PharPoint Research, Inc.: Current Employment. Kumar: Kronos Bio, Inc.: Current Employment, Current equity holder in publicly-traded company. Bray: Kronos Bio, Inc.: Consultancy. DiMartino: Kronos Bio, Inc.: Current Employment, Current equity holder in publicly-traded company. Stock: Pfizer: Consultancy, Honoraria, Research Funding; amgen: Honoraria; agios: Honoraria; jazz: Honoraria; kura: Honoraria; kite: Honoraria; morphosys: Honoraria; servier: Honoraria; syndax: Consultancy, Honoraria; Pluristeem: Consultancy, Honoraria. OffLabel Disclosure: Entospletinib is an investigational therapy

Dose-dense induction and up-front consolidation with autologous stem cell transplantation (ASCT) remain controversial issues when treating patients with high-risk diffuse large B-cell lymphoma. GELA designed a randomized phase 2 trial evaluating the efficacy of either rituximab, doxorubicin, cyclophosphamide, vindesine, bleomycin, prednisone (R-ACVBP) or rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone (R-CHOP14) induction and a positron emission tomography (PET)-driven ASCT or standard immunochemotherapy (SIC) consolidation in age-adjusted international prognosis index 2 (aaIPI2)-aaIPI3 patients. PET was performed at baseline, after 2 (PET2) and 4 (PET4) induction cycles, and centrally assessed using international harmonization project (IHP) criteria. PET2-/PET4- patients were assigned SIC, PET2+/PET4- patients were assigned ASCT, and PET4+ patients were treated with the investigator's choice. The primary end-point was the 2007 international working group complete response (CR) rate after induction. Change in maximum standard uptake value (ΔSUVmax) after PET assessment was explored. Two hundred eleven patients were randomly assigned to R-ACVBP (n = 109) or R-CHOP14 (n = 102). PET4-/CR rates were 53%/47% with R-ACVBP and 41%/39% with R-CHOP14 (CR 95% confidence interval [CI], 38%-67% and 28%-54%, respectively; P = .076). Consolidation in the R-ACVBP and R-CHOP14 groups was SIC in 26% and 23% of patients and ASCT in 28% and 18% of patients, respectively. PET4 positivity was higher with R-CHOP14 vs R-ACVBP (54% vs 41%; P = .08), leading to more salvage therapy (37% vs 26%; P = .07) and lower event-free survival (EFS; 4-year EFS, 31% vs 43%; P 70% was associated with better outcome (4-year PFS, 84% vs 35%; 4-year OS, 91% vs 57%; P < .0001), whatever the consolidation. Superiority of R-ACVBP over R-CHOP14 was not established, as IHP criteria did not properly reflect disease control. ΔSUVmax may help better select patients needing an alternative to SIC, including ASCT.

Background: CPX-351 is a liposomal encapsulation of daunorubicin and cytarabine in a 1:5 molar ratio. In a randomized phase 3 study (CPX-351-301) conducted in older adults (60 to 75 years old) with newly diagnosed, high-risk and/or secondary AML, CPX-351 induction therapy was superior to standard 7+3 with improved rates of complete remission (CR) and overall survival (OS). In both older adults and high-risk AML, allogeneic hematopoietic cell transplantation (HCT) is frequently the preferred post-remission strategy owing to the high rates of relapse and poor overall survival with conventional chemotherapy approaches. After a median follow-up of 20.7 months, the primary pre-planned analysis found that more patients randomized to CPX-351 underwent HCT and an exploratory landmark survival analysis from the time of HCT favored CPX-351 (HR = 0.46 [95% CI: 0.24, 0.89]; one-sided P = 0.009). However, the initial protocol did not collect data related to HCT and the basis for improved HCT outcomes with CPX-351 was previously unknown. Here we present a detailed analysis of HCT outcomes in patients enrolled in the CPX-351-301 study with 5-years of follow-up. Methods: Patients age 60 to 75 years with high-risk and/or secondary AML were randomized in a 1:1 fashion to receive CPX-351 or 7+3 as induction and consolidation chemotherapy (Lancet J et al, JCO 2018). The protocol was amended to collect additional HCT-specific information, including donor and HCT characteristics and post-HCT outcomes, including rates of relapse and GVHD. Post-HCT outcomes including relapse, GVHD, and death were analyzed as competing events. Results: Of 309 randomized patients in the CPX-351-301 study, more patients achieved CR/CRi with CPX-351 vs 7+3 (48% vs 33%) allowing more patients to proceed to HCT (35% vs 25%) and more patients to proceed to HCT in remission (CPX-351: 41/73 [56%]; 7+3: 24/52 [46%]). The median age was 66 years with CPX-351 vs 65 years with standard induction among the transplanted cohorts; 16 patients in the CPX-351 transplanted arm were over the age of 70 compared to only 6 in the 7+3 arm. Other pre-HCT patient characteristics were balanced between the CPX-351 and 7+3 groups, including ECOG performance status (8% vs 5% with ECOG PS of 2), HCT-CI (median 4 vs 3), donor type (matched unrelated donor 49% vs 49%), and conditioning regimen intensity (myeloablative [17% vs 13%] vs reduced-intensity conditioning [43% vs 46%]). The Kaplan-Meier-estimated 3-year survival rate among transplanted patients was 56% with CPX-351 vs 23% with 7+3 (Figure 1A). The differences in survival consistently favored CPX-351 across patient age, AML subtype, disease status, donor type, and conditioning intensity (Figure 1B). Differences in OS were driven by a large reduction in non-relapse mortality (HR = 0.42 [95% CI: 0.21, 0.86]; Figure 1D). The cumulative incidence of acute GVHD with death as a competing event at 6 months from HCT date was 0.49 (95% CI: 0.35, 0.62) in the CPX-351 arm and 0.38 (95% CI: 0.23, 0.53) in the 7+3 arm. Conclusions: Analysis of HCT outcomes in patients enrolled in the CPX-351-301 study demonstrated that treatment with CPX-351 in older adults with high-risk and/or secondary AML resulted in more patients bridged to HCT and more patients transplanted in CR/CRi compared to 7+3, with improved OS in transplanted patients. The pattern of HCT outcomes suggests improved disease control with CPX-351 induction allowing higher HCT rates, but more importantly improved tolerability with less non-relapse mortality; this data supports the development of CPX-351 in other high-risk AML populations in which allogeneic HCT is the preferred post-remission strategy. Figure Disclosures Uy: Genentech: Consultancy; Agios: Consultancy; Pfizer: Consultancy; Daiichi Sankyo: Consultancy; Astellas Pharma: Honoraria; Jazz Pharmaceuticals: Consultancy. Lin:Abbvie: Research Funding; Pfizer: Research Funding; Trovagene: Research Funding; Prescient Therapeutics: Research Funding; Tolero Pharmaceuticals: Research Funding; Seattle Genetics: Research Funding; Ono Pharmaceutical: Research Funding; Genetech-Roche: Research Funding; Incyte: Research Funding; Jazz: Research Funding; Mateon Therapeutics: Research Funding; Gilead Sciences: Research Funding; Celyad: Research Funding; Celgene: Research Funding; Bio-Path Holdings: Research Funding; Astellas Pharma: Research Funding; Aptevo: Research Funding. Wieduwilt:Reata Pharmaceuticals: Current equity holder in publicly-traded company; Daiichi Sankyo: Membership on an entity's Board of Directors or advisory committees; Shire: Research Funding; Merck: Research Funding; Leadiant: Research Funding; Amgen: Research Funding; Macrogeneics: Research Funding. Ryan:Jazz Pharmaceuticals: Current Employment, Current equity holder in publicly-traded company. Faderl:Jazz Pharmaceuticals: Current Employment, Current equity holder in publicly-traded company. Lancet:Abbvie: Consultancy; Agios Pharmaceuticals: Consultancy, Honoraria; Astellas Pharma: Consultancy; Celgene: Consultancy, Research Funding; Daiichi Sankyo: Consultancy; ElevateBio Management: Consultancy; Jazz Pharmaceuticals: Consultancy; Pfizer: Consultancy.

Introduction: Outcomes for acute myeloid leukemia (AML) among older patients has remained largely unchanged for decades. Long-term survival for patients aged >60 years is poor (median survival 10.5 months). Targeting the proteasome in AML is attractive, since leukemia stem cells have demonstrated sensitivity to proteasome inhibition in preclinical models, perhaps through down regulation of nuclear NF-KB (Guzman, Blood 2001). AML cell lines are susceptible to synergistic cytotoxicity when bortezomib, a proteasome inhibitor, is combined with daunorubicin and cytarabine. We have shown that adding bortezomib to standard treatment in AML results in a high remission rate, although grade 2 sensory neurotoxicity was noted in approximately 12% of treated patients. A newer generation proteasome inhibitor, ixazomib, is less frequently associated with neurotoxicity, and, therefore, was selected for combination with conventional chemotherapy in this phase I trial. The primary objective of this study was to determine the maximum tolerated dose (MTD) of ixazomib in combination with conventional induction and consolidation chemotherapy for AML. Herein are the initial results of this trial. Methods: Adults >60 years of age with newly diagnosed AML were screened for eligibility. Patients with secondary AML were eligible, including those with prior hypomethylating agent therapy for myelodysplastic syndromes (MDS). We excluded those with promyelocytic leukemia. There were 2 phases in this study. In the first phase (A), the induction treatment consisted of the following: cytarabine 100 mg/m2/day by continuous IV infusion, Days 1-7; daunorubicin 60 mg/m2/day IV, Days 1, 2, 3, and ixazomib was provided orally at the cohort dose, Days 2, 5, 9, and 12. Consolidaton or transplant was at the discretion of the treating physician in phase A. In the second phase (B), induction was the same as that with the determined MTD of ixazomib. All patients were to be treated with the following consolidation: cytarabine at 2 g/m2/day, days 1-5 with ixazomib on days 2, 5, 9, and 12 at the cohort dose for consolidation. A standard 3 + 3 patient cohort dose escalation design was used to determine whether the dose of ixazomib could be safely escalated in 3 cohorts (1.5 mg/day, 2.3 mg/day, 3.0 mg/day), initially in induction (phase A) and subsequently in consolidation (phase B). The determined MTD of ixazomib in the first portion (A) of the trial was used during induction in the second portion (B), which sought to determine the MTD for ixazomib during consolidation. Secondary objectives included rate of complete remission, disease-free survival, and overall survival (OS). Results: Thirty-six patients have been enrolled on study, and 28 have completed dose levels A-1 through A-3 and B1 through B-2. Full information on cohort B-3 has not yet been obtained, hence, this report covers the experience with the initial 28 patients, cohorts A-1 through B-2. There were 12 (43%) patients among the 28 with secondary AML, either with prior hematologic malignancy or therapy-related AML. Nineteen patients (68%) were male, and the median age was 68 years (range 61-80 years). There have been no grade 5 toxicities due to study drug. Three patients died early due to leukemia, 2 of which were replaced for assessment of the MTD. Nearly all the grade 3 and 4 toxicities were hematologic (Table). There was 1 DLT (grade 4 platelet count decrease extending beyond Day 42). There has been no grade 3 or 4 neurotoxicity with ixazomib to date. Among the 28 patients in the first 5 cohorts, 22 achieved complete remissions (CR) and 2 achieved CRi, for a composite remission rate (CCR) of 86%. Among the 12 patients with secondary AML 8 achieved CR and 2 achieved CRi, for a CCR of 83%. The median OS for the 28 patients has not been reached (graph). The 18-month OS estimate was 65% [90% CI, 50-85%]. Conclusions: The highest dose level (3 mg) of ixazomib planned for induction in this trial has been reached safely. For consolidation there have been no serious safety issues in the first 2 cohorts with a dose up to 2.3 mg, apart from 1 DLT in the form of delayed platelet count recovery. The recommended phase 2 dose of ixazomib for induction is 3 mg. Accrual to cohort B-3 is ongoing. Notably, to date, no grade 3 or 4 neurotoxicity has been encountered. The remission rate in this older adult population with the addition of ixazomib to standard chemotherapy appears favorable. Figure Disclosures Amrein: Amgen: Research Funding; AstraZeneca: Consultancy, Research Funding; Takeda: Research Funding. Attar:Aprea Therapeutics: Current Employment. Brunner:Jazz Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees; Forty-Seven Inc: Membership on an entity's Board of Directors or advisory committees; AstraZeneca: Research Funding; Takeda: Research Funding; Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Research Funding. Hobbs:Constellation: Honoraria, Research Funding; Novartis: Honoraria; Incyte: Research Funding; Merck: Research Funding; Bayer: Research Funding; Jazz: Honoraria; Celgene/BMS: Honoraria. Neuberg:Celgene: Research Funding; Madrigak Pharmaceuticals: Current equity holder in publicly-traded company; Pharmacyclics: Research Funding. Fathi:Blueprint: Consultancy; Boston Biomedical: Consultancy; BMS/Celgene: Consultancy, Research Funding; Novartis: Consultancy; Kura Oncology: Consultancy; Trillium: Consultancy; Amgen: Consultancy; Seattle Genetics: Consultancy, Research Funding; Abbvie: Consultancy; Pfizer: Consultancy; Newlink Genetics: Consultancy; Forty Seven: Consultancy; Trovagene: Consultancy; Kite: Consultancy; Daiichi Sankyo: Consultancy; Astellas: Consultancy; Amphivena: Consultancy; PTC Therapeutics: Consultancy; Agios: Consultancy, Research Funding; Takeda: Consultancy, Research Funding; Jazz: Consultancy. OffLabel Disclosure: Ixazomib is FDA approved for multiple myeloma. We are using it in this trial for acute myeloid leukemia.

Background: Gilteritinib, an oral FMS-like tyrosine kinase 3 (FLT3) inhibitor, demonstrated antileukemic responses in patients with FLT3-mutated (FLT3mut+) relapsed/refractory acute myeloid leukemia (AML). We report final results from a phase 1 study of once-daily oral gilteritinib plus intravenous (IV) chemotherapy in patients with newly diagnosed AML. Methods: This 4-part, open-label, phase 1 study (NCT02236013) assessed the safety/tolerability and antileukemic effects of gilteritinib plus 7+3 induction and high-dose cytarabine consolidation chemotherapy, and as single-agent maintenance therapy in adults with newly diagnosed AML. In part 1, successive cohorts of 3-6 patients received 40-200 mg/d gilteritinib (Days 4-17) and ≤2 cycles of induction (cytarabine 100 mg/m2/d IV, Days 1-7; idarubicin 12 mg/m2/d IV, Days 1-3). In part 2, patients (n=33, of which at least 15 were FLT3mut+) received the recommended 120 mg/d gilteritinib expansion dose and ≤2 cycles of the part 1 induction schedule. In part 3, patients were stratified into 2 cohorts: one receiving treatment from part 2 (n=7) and the other receiving treatment that replaced idarubicin with daunorubicin (90 mg/m2/d IV, Days 1-3; n=7). In part 4, patients (n=12) received the same induction as the part 3/daunorubicin cohort (with a reduction in cycle 2 to daunorubicin 45 mg/m2/d). During consolidation, patients received ≤3 cycles of cytarabine (1.5 g/m2 every 12 hours; Days 1, 3, and 5) and gilteritinib (Days 1-14 for parts 1-3; Days 1-56 for part 4) at the induction dose. Gilteritinib was given once daily in 28-day cycles for up to 26 cycles as maintenance therapy (maintenance phase is still ongoing). Patients achieving composite complete remission (CRc) or partial remission could undergo hematopoietic stem cell transplant (HSCT) and resume maintenance gilteritinib treatment post-HSCT. Results: As of 23 June 2020, 80 patients were allocated to treatment (safety analysis set, n=79); median age was 59.0 y (range, 23-77) and most were male (62.0%). Median follow-up for overall survival (OS) was 35.8 mo. Dose-limiting toxicities are provided in Table 1. The maximum tolerated dose was 120 mg/d. Serious treatment-related adverse events (AEs) and AEs leading to discontinuation of gilteritinib occurred in 12.7% (n=10) and 5.1% (n=4) of patients, respectively. One (1.3%) death occurred across all treatment phases. Grade ≥3 nonhematologic AEs (≥10% of patients) were increased alanine aminotransferase (13.9%), pneumonia (13.9%), sepsis (11.4%), and bacteremia (11.4%). At the end-of-induction time point, there were 44 (55.7%) total FLT3mut+ patients across all dose groups and 38 (48.1%) patients who received gilteritinib 120 mg/d. Investigator-reported CRc was achieved by 81.8% of patients across all dose groups (n=36) and 81.6% among patients who received gilteritinib 120 mg/d (n=31; Table 2). Anthracycline choice had no clear impact on CRc rate, although the number of patients in these cohorts was low. In FLT3mut+ patients who achieved CRc in any dose group, median (95% CI) duration of CRc and disease-free survival were 14.1 (4.0-29.9) and 15.3 (9.8-not reached) mo, respectively. Median OS for FLT3mut+ patients has not been reached. The survival probability (95% CI) in all FLT3mut+ patients at weeks 8, 12, 26, 52, and 104 were 97.7% (84.6%-99.7%), 95.3% (82.5%-98.8%), 92.9% (79.6%-97.7%), 83.1% (67.7%-91.5%), and 71.8% (54.6%-83.4%), respectively. In patients with FLT3 internal tandem duplication (ITD)-positive AML achieving CRc, mutational clearance (summed FLT3 ITD signal ratio of ≤10-4 after induction or consolidation) was achieved by 70% (n/N=16/23) of patients receiving a gilteritinib dose of ≥120 mg. HSCT occurred in 30.4% of the total population (n/N=24/79). Analysis of plasma inhibitory activity and pharmacokinetics of gilteritinib will be available at presentation. Conclusions: Gilteritinib plus induction and consolidation chemotherapy is well tolerated in patients with newly diagnosed AML. Favorable antileukemic responses were observed in FLT3mut+ patients regardless of anthracycline type or gilteritinib administration schedule, with a mutational clearance rate of 70.0%. Based on these results, randomized clinical trials of induction and consolidation chemotherapy plus gilteritinib vs midostaurin in FLT3mut+ AML patients have been initiated. Disclosures Pratz: AbbVie: Other: Scientific Advisory Board, Research Funding; Astellas: Other: Scientific Advisory Board, Research Funding; Boston BioMedical: Consultancy; Celgene: Other: Scientific Advisory Board; Agios: Other: Scientific Advisory Board, Research Funding; Jazz Pharmaceutical: Consultancy; Millennium: Research Funding; Daiichi Sankyo: Research Funding. Cherry:Pfizer: Other: Advisory Board; BMS: Other: Advisory Board; Kite: Other: Advisory Board. Altman:PeerView: Consultancy; ASH: Consultancy; Syros: Consultancy; Janssen: Consultancy; Genentech: Research Funding; Amphivena: Research Funding; Amgen: Research Funding; Aprea: Research Funding; ImmunoGen: Research Funding; Celgene: Research Funding; Boehringer Ingelheim: Research Funding; PrIME Oncology: Consultancy; Immune Pharmaceuticals: Consultancy; Novartis: Consultancy; Glycomimetics: Other: Data safety and monitoring committee; Daiichi Sankyo: Other: Advisory Board - no payment but was reimbursed for travel; Kura Oncology: Other: Scientific Advisory Board - no payment accepted, Research Funding; Kartos: Research Funding; AbbVie: Other: advisory board, Research Funding; Fujifilm: Research Funding; BioSight: Other: No payment but was reimbursed for travel , Research Funding; Bristol-Myers Squibb: Consultancy; Astellas: Other: Advisory Board, Speaker (no payment), Steering Committee (no payment), Research Funding; Cancer Expert Now: Consultancy; Agios: Other: advisory board, Research Funding; Theradex: Other: Advisory Board; France Foundation: Consultancy. Cruz:Takeda: Speakers Bureau. Jurcic:Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; BMS: Consultancy, Research Funding; Daiichi-Sankyo: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees; Arog Pharmaceuticals: Research Funding; Astellas: Research Funding; Forma Therapeutics: Research Funding; Genentech: Research Funding; Kura Oncology: Research Funding; PTC Therapeutics: Research Funding; Syros Pharmaceuticals: Research Funding; AbbVie: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding. Levis:Menarini: Honoraria; Amgen: Honoraria; FujiFilm: Honoraria, Research Funding; Daiichi-Sankyo: Honoraria; Astellas: Honoraria, Research Funding. Lin:Pfizer: Research Funding; Bio-Path Holdings: Research Funding; Abbvie: Research Funding; Seattle Genetics: Research Funding; Tolero Pharmaceuticals: Research Funding; Ono Pharmaceutical: Research Funding; Prescient Therapeutics: Research Funding; Incyte: Research Funding; Genetech-Roche: Research Funding; Gilead Sciences: Research Funding; Aptevo: Research Funding; Celyad: Research Funding; Celgene: Research Funding; Astellas Pharma: Research Funding; Mateon Therapeutics: Research Funding; Jazz: Research Funding; Trovagene: Research Funding. Perl:Bayer HealthCare Pharmaceuticals: Research Funding; Syndax: Consultancy, Honoraria; Jazz: Honoraria, Other; Arog Pharmaceuticals Inc: Other: uncompensated consulting, travel costs for meetings; Biomed Valley Discoveries: Research Funding; Agios: Consultancy, Honoraria, Other; FUJIFILM Pharmaceuticals USA, Inc: Research Funding; AbbVie Inc: Consultancy, Honoraria, Other, Research Funding; Loxo Oncology Inc, a wholly owned subsidiary of Eli Lilly & Company: Consultancy, Honoraria, Other; Takeda: Honoraria, Other: Travel costs for meeting; Astellas: Consultancy, Honoraria, Other: writing/editorial support, travel costs for meeting presentations related to study, Research Funding; Leukemia & Lymphoma Society, Beat AML: Consultancy; New Link Genetics: Honoraria, Other; Daiichi Sankyo: Consultancy, Honoraria, Other: Writing/editorial support, travel costs for meetings, Research Funding; FORMA Therapeutics: Consultancy, Honoraria, Other; Actinium Pharmaceuticals Inc: Consultancy, Honoraria, Research Funding; Novartis: Honoraria, Other, Research Funding. Podoltsev:Arog Pharmaceuticals: Research Funding; Astex Pharmaceuticals: Research Funding; Jazz Pharmaceuticals: Research Funding; Sunesis Pharmaceuticals: Research Funding; Boehringer Ingelheim: Research Funding; Daiichi Sankyo: Research Funding; Astellas Pharma: Research Funding; CTI biopharma: Consultancy, Honoraria, Research Funding; Bristol-Myers Squib: Consultancy, Honoraria; Genentech: Research Funding; Novartis: Consultancy, Honoraria; Celgene: Consultancy, Honoraria, Research Funding; Samus Therapeutics: Research Funding; Agios Pharmaceuticals: Consultancy, Honoraria; Pfizer: Consultancy, Honoraria, Research Funding; Incyte: Consultancy, Honoraria; Blueprint Medicines: Consultancy, Honoraria; Alexion: Consultancy, Honoraria; Kartos Therapeutics: Research Funding; AI Therapeutics: Research Funding. Schiller:Abbvie: Research Funding; Actinium: Research Funding; Ariad: Research Funding; Amgen: Consultancy, Current equity holder in publicly-traded company, Research Funding, Speakers Bureau; AstraZeneca: Consultancy; Incyte: Consultancy, Research Funding, Speakers Bureau; Novartis: Consultancy, Research Funding; Ono Pharma: Consultancy; Kite Pharma: Research Funding; Stemline: Speakers Bureau; Gilead: Speakers Bureau; Celgene: Research Funding, Speakers Bureau; Sanofi: Speakers Bureau; Agios: Consultancy, Research Funding, Speakers Bureau; DeltaFly: Research Funding; Deciphera: Research Funding; Daiichi Sankyo: Research Funding; Cyclacel: Research Funding; Constellation: Research Funding; Celator: Research Funding; Astellas Pharma: Honoraria, Research Funding; Bristol-Myers Squibb: Current equity holder in publicly-traded company, Research Funding; Forma: Research Funding; FujiFilm: Research Funding; Gamida: Research Funding; Genentech-Roche: Research Funding; Geron: Research Funding; Jazz Pharmaceuticals: Research Funding; Karyopharm: Research Funding; Mateon: Research Funding; MedImmune: Research Funding; Onconova: Research Funding; Pfizer: Current equity holder in publicly-traded company, Research Funding; Regimmune: Research Funding; Samus: Research Funding; Sangamo: Research Funding; Tolero: Research Funding; Trovagene: Research Funding; Kaiser Permanente: Consultancy; Johnson & Johnson: Current equity holder in publicly-traded company. Hill:Targeted Molecular Diagnostics: Patents & Royalties: US7862995; Astellas: Current Employment; Ligacept, LLC: Current equity holder in publicly-traded company, Patents & Royalties: US9051388, US9683222. James:Astellas: Current Employment. Lu:Astellas: Current Employment. Tiu:Astellas Pharma Global Development: Current Employment; Eli Lilly & Company: Current equity holder in publicly-traded company, Ended employment in the past 24 months. OffLabel Disclosure: New Indication

International audience; Guidelines for monitoring multiple myeloma (MM) patients expressing light chains only (light-chain MM [LCMM]) rely on measurements of monoclonal protein in urine. Alternatively, serum free light chain (sFLC) measurements have better sensitivity over urine methods, however, demonstration that improved sensitivity provides any clinical benefit is lacking. Here, we compared performance of serum and urine measurements in 113 (72κ, 41λ) newly diagnosed LCMM patients enrolled in the Intergroupe Francophone du Myélome (IFM) 2009 trial. All diagnostic samples (100%) had an abnormal κ:λ sFLC ratio, and involved (monoclonal) FLC (iFLC) expressed at levels deemed measurable for monitoring (≥100 mg/L). By contrast, only 64% patients had measurable levels of monoclonal protein (≥200 mg per 24 hours) in urine protein electrophoresis (UPEP). After 1 and 3 treatment cycles, iFLC remained elevated in 71% and 46% of patients, respectively, whereas UPEP reported a positive result in 37% and 18%; all of the patients with positive UPEP at cycle 3 also had elevated iFLC levels. Importantly, elevated iFLC or an abnormal κ:λ sFLC ratio after 3 treatment cycles associated with poorer progression-free survival (P = .006 and P < .0001, respectively), whereas positive UPEP or urine immunofixation electrophoresis (uIFE) did not. In addition, patients with an abnormal κ:λ sFLC ratio had poorer overall survival (P = .022). Finally, early normalization of κ:λ sFLC ratio but not negative uIFE predicted achieving negative minimal residual disease, as determined by flow cytometry, after consolidation therapy (100% positive predictive value). We conclude that improved sensitivity and prognostic value of serum over urine measurements provide a strong basis for recommending the former for monitoring LCMM patients.

Mantle cell lymphoma (MCL) is a rare and aggressive form of non-Hodgkin lymphoma. It is predominantly a disease of older individuals, with a median age at presentation of ∼70 years. For the majority of patients, the management revolves around immuno-chemotherapy often followed by maintenance rituximab, and at relapse, a range of options are available. For the younger patient, it is possible to be more intensive with therapy, consolidate responses with high-dose procedures, and in a few there might be the prospect of a cure. The incorporation of high-dose cytarabine into the treatment algorithm has had a major impact on outcomes, with approximately half of the patients alive at 10 years whether an autologous stem cell transplant is adopted or not. Allogeneic transplantation produces some very durable responses in the relapsed setting and has a potential role up front in the highest-risk patients. However, with the advent of Bruton tyrosine kinase inhibitor and other highly effective nontraditional chemotherapeutic approaches, there is the potential for the management of this disease to change fundamentally over the next few years.

Despite the recent substantial improvement of clinical outcome in mantle cell lymphoma (MCL), resistance to immunochemotherapy and common relapses are challenges for long-term tumor control. The assessment of minimal residual disease (MRD) by real-time quantitative polymerase chain reaction has emerged as a widely feasible and standardized tool for direct assessment of therapy-induced reduction of tumor burden and regrowth after cytotoxic treatment in MCL, with much improved sensitivity compared with conventional staging procedures. Several studies have shown that intensification of initial treatment, which has resulted in improved clinical outcome, is immediately reflected in higher molecular remission rates; they have also shown that high-dose consolidation might not be able to compensate for less intensive induction regimens. Persistence or reappearance of MRD in clinical remission proved to be highly predictive for imminent clinical relapse associated with shorter overall survival. Therefore, the investigation of novel MRD-guided treatment strategies aimed at early eradication of MRD and pre-emptive treatment of molecular relapse seems warranted. Furthermore, the integration of MRD assessment into clinical response criteria could result in a more specific and potentially earlier end point for treatment efficacy. New technical developments such as high-throughput sequencing will further enhance the wide applicability of MRD detection in MCL.

The clinical benefit of adding FMS-like tyrosine kinase-3 (FLT3)-directed small molecule therapy to standard first-line treatment of acute myeloid leukemia (AML) has not yet been established. As part of the UK AML15 and AML17 trials, patients with previously untreated AML and confirmed FLT3-activating mutations, mostly younger than 60 years, were randomly assigned either to receive oral lestaurtinib (CEP701) or not after each of 4 cycles of induction and consolidation chemotherapy. Lestaurtinib was commenced 2 days after completing chemotherapy and administered in cycles of up to 28 days. The trials ran consecutively. Primary endpoints were overall survival in AML15 and relapse-free survival in AML17; outcome data were meta-analyzed. Five hundred patients were randomly assigned between lestaurtinib and control: 74% had FLT3-internal tandem duplication mutations, 23% FLT3-tyrosine kinase domain point mutations, and 2% both types. No significant differences were seen in either 5-year overall survival (lestaurtinib 46% vs control 45%; hazard ratio, 0.90; 95% CI 0.70-1.15; P = .3) or 5-year relapse-free survival (40% vs 36%; hazard ratio, 0.88; 95% CI 0.69-1.12; P = .3). Exploratory subgroup analysis suggested survival benefit with lestaurtinib in patients receiving concomitant azole antifungal prophylaxis and gemtuzumab ozogamicin with the first course of chemotherapy. Correlative studies included analysis of in vivo FLT3 inhibition by plasma inhibitory activity assay and indicated improved overall survival and significantly reduced rates of relapse in lestaurtinib-treated patients who achieved sustained greater than 85% FLT3 inhibition. In conclusion, combining lestaurtinib with intensive chemotherapy proved feasible in younger patients with newly diagnosed FLT3-mutated AML, but yielded no overall clinical benefit. The improved clinical outcomes seen in patients achieving sustained FLT3 inhibition encourage continued evaluation of FLT3-directed therapy alongside front-line AML treatment. The UK AML15 and AML17 trials are registered at www.isrctn.com/ISRCTN17161961 and www.isrctn.com/ISRCTN55675535 respectively.

The introduction of new drugs with less severe toxicity profiles than those of conventional antimyeloma agents allowed the evaluation of continuous therapy compared with fixed duration therapy. In transplant-eligible patients, consolidation therapy with bortezomib or bortezomib-based regimens showed significant progression-free survival (PFS) benefit in cytogenetic standard-risk patients and to a lesser extent, high-risk patients. Continuous therapy with lenalidomide maintenance treatment after autologous stem cell transplantation resulted in a significant survival gain. In transplant noneligible patients, continuous lenalidomide-dexamethasone therapy improved survival over fixed duration melphalan-prednisone-thalidomide. The concept of prolonged treatment in elderly patients is supported by some other studies, but most of them revealed a gain in PFS only. Young patients with unfavorable prognosis show a greater willingness to accept long-term treatment, whereas the readiness to undergo such treatments and the benefits therefrom decline with increasing age and decreasing fitness, rendering fixed duration therapy a suitable option in elderly frail patients.

In the S0313 trial, we evaluated the impact of adding ibritumomab tiuxetan consolidation to 3 cycles of standard cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) chemotherapy plus involved field radiotherapy (IFRT) in patients with limited-stage aggressive B-cell non-Hodgkin lymphoma (LD-NHL). Patients with at least 1 stage-modified adverse risk factor (nonbulky stage II, age >60 years, elevated lactate dehydrogenase, or World Health Organization performance status of 2) were treated with CHOP on days 1, 22, and 43, followed 3 weeks later by 40 to 50 Gy of IFRT. An ibritumomab tiuxetan regimen was initiated 3 to 6 weeks following IFRT. Forty-six patients were registered and eligible, with median follow-up of 7.3 years. The progression-free survival estimate is 89% at 2 years, 82% at 5 years, and 75% at 7 years. The overall survival estimate is 91% at 2 years, 87% at 5 years, and 82% at 7 years. Grade 4 adverse events occurring more than once included neutropenia (8), leukopenia (5), and lymphopenia (2). Febrile neutropenia was observed in 4 patients. No cases of treatment-related myeloid neoplasms were noted. In conclusion, patients with high-risk LD-NHL treated with 3 cycles of CHOP plus IFRT followed by ibritumomab tiuxetan consolidation had outcomes that compare favorably to our historical experience. The clinical trial was registered at www.clinicaltrials.gov as #NCT00070018.

The Cancer and Leukemia Group B (CALGB), now part of the Alliance for Clinical Trials in Oncology, conducted a multicenter, single-arm, phase 2 study in patients ≥60 years with FMS-like tyrosine kinase 3 (FLT3)-mutated acute myeloid leukemia (AML). In this study, sorafenib was added to daunorubicin and cytarabine-based induction and consolidation chemotherapy and was also continued for 12 months of maintenance therapy. The primary end point of the study was overall survival (OS) at 1 year in the FLT3 internal tandem duplication (FLT3-ITD) cohort. Fifty-four patients with a median age of 67 years (range, 60.3-82.7 years) were enrolled; 39 were FLT3-ITD patients (71%) and 15 were FLT3-TKD (29%) patients. The observed 1-year OS (95% confidence interval [CI]) was 62% (45%-78%) for the FLT3-ITD patients (meeting the primary end point 62% vs 30% for a historical control group, P < .0001) and 71% (42%-92%) for the FLT3-TKD patients. The median disease-free survival and OS were 12.2 months (95% CI, 5-16.9) and 15.0 months (95% CI, 10.4-20.1), respectively, in the FLT3-ITD group and 9.6 (95% CI, 1.9 to not available [NA]) and 16.2 months (95% CI, 5.0 to NA) for the FLT3-TKD group. This study suggests that the addition of sorafenib to chemotherapy for FLT3-ITD AML is feasible and may improve the survival of older adults with FLT3-mutated AML. This trial was registered at www.clinicaltrials.gov as #NCT01253070.

Background: The minimal or measurable residual disease (MRD) status post induction-consolidation is widely accepted as major surrogate endpoint that correlates with outcome in adult patients with newly diagnosed acute lymphoblastic leukemia (ALL). However, the optimal time-points of MRD assessment at complete remission (CR) or later during consolidation and its impact on outcome remain unclear. Methods: We performed a retrospective chart review of 419 newly diagnosed adult patients with Philadelphia negative B-cell ALL who received treatment at the M.D. Anderson Cancer Center between 01/2000 and 01/2015 (Figure 1). Overall, 394 of 419 (94%) patients achieved CR. Two hundred and fifteen patients (51%) had available MRD assessment (by multicolor flow cytometry) at CR (1st time-point: median 24 days) and first post-CR MRD assessment (2nd time-point: median 3.6 months), and constitute the current studied cohort. MRD responses were stratified as MRD negative (undetectable), low-positive (≤0.1%), and high-positive (>0.1%). Results: The median age for the study cohort (n=215) was 37 years (range 15-86), and 17% (n=37) had unfavorable cytogenetic profile, such as complex karyotype (n=9), KMT2A (MLL) rearrangement (n=14), and low hypodiploidy/near triploidy (n=14) (Table 1). At first time-point (1TP), 148 patients (68%) were MRD negative and 67 (32%) were positive (Figure 2). Of the 148 patients with negative MRD at 1TP, 147 (99%) maintained it through second time-point (2TP). Fourteen of 16 (88%) patients with low-positive MRD and 33 of 51 (64%) with high-positive MRD at 1TP became MRD negative at 2TP. Patients who were MRD negative at both time-points, early MRD responders, had the 3-year event-free survival (EFS) and overall survival (OS) rates of 65% and 76%, respectively (Table 2). Patients with improved MRD status from positive to negative, late MRD responders, had lower 3-year EFS and OS rates, 42% and 58%, respectively (Figure 3, p Conclusion: The early achievement of MRD negative CR is a strong predictive for survival. Innovative combinations of conventional chemotherapy and targeted agents that induce early MRD eradication may have the potential to improve cure rates in adult ALL. Disclosures Kantarjian: Daiichi-Sankyo: Research Funding; Astex: Research Funding; Actinium: Honoraria, Membership on an entity's Board of Directors or advisory committees; Pfizer: Honoraria, Research Funding; Cyclacel: Research Funding; Novartis: Research Funding; Ariad: Research Funding; Immunogen: Research Funding; Amgen: Honoraria, Research Funding; Agios: Honoraria, Research Funding; BMS: Research Funding; Takeda: Honoraria; Jazz Pharma: Research Funding; AbbVie: Honoraria, Research Funding. Khoury:Kiromic: Research Funding; Angle: Research Funding; Stemline Therapeutics: Research Funding. Ravandi:Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Xencor: Consultancy, Research Funding; Cyclacel LTD: Research Funding; Menarini Ricerche: Research Funding; Macrogenix: Consultancy, Research Funding; Selvita: Research Funding. Short:AstraZeneca: Consultancy; Takeda Oncology: Consultancy, Research Funding; Amgen: Honoraria. Loghavi:GLG Consultants: Consultancy; AlphaSights: Consultancy; MDACC: Employment. Cortes:BiolineRx: Consultancy; Novartis: Consultancy, Honoraria, Research Funding; Forma Therapeutics: Consultancy, Honoraria, Research Funding; Merus: Consultancy, Honoraria, Research Funding; Astellas Pharma: Consultancy, Honoraria, Research Funding; Jazz Pharmaceuticals: Consultancy, Research Funding; Daiichi Sankyo: Consultancy, Honoraria, Research Funding; Pfizer: Consultancy, Honoraria, Research Funding; Takeda: Consultancy, Research Funding; Sun Pharma: Research Funding; Immunogen: Consultancy, Honoraria, Research Funding; Bristol-Myers Squibb: Consultancy, Research Funding; Biopath Holdings: Consultancy, Honoraria. Garcia-Manero:Amphivena: Consultancy, Research Funding; Helsinn: Research Funding; Novartis: Research Funding; AbbVie: Research Funding; Celgene: Consultancy, Research Funding; Astex: Consultancy, Research Funding; Onconova: Research Funding; H3 Biomedicine: Research Funding; Merck: Research Funding. Kadia:Pfizer: Membership on an entity's Board of Directors or advisory committees, Research Funding; Jazz: Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Research Funding; Bioline RX: Research Funding; BMS: Research Funding; Amgen: Membership on an entity's Board of Directors or advisory committees, Research Funding; Genentech: Membership on an entity's Board of Directors or advisory committees; Pharmacyclics: Membership on an entity's Board of Directors or advisory committees; Takeda: Membership on an entity's Board of Directors or advisory committees; AbbVie: Consultancy, Research Funding. Sasaki:Otsuka: Honoraria; Pfizer: Consultancy. Konopleva:Calithera: Research Funding; Stemline Therapeutics: Consultancy, Honoraria, Research Funding; Forty-Seven: Consultancy, Honoraria; Eli Lilly: Research Funding; AbbVie: Consultancy, Honoraria, Research Funding; Cellectis: Research Funding; Amgen: Consultancy, Honoraria; F. Hoffman La-Roche: Consultancy, Honoraria, Research Funding; Genentech: Honoraria, Research Funding; Ascentage: Research Funding; Kisoji: Consultancy, Honoraria; Reata Pharmaceuticals: Equity Ownership, Patents & Royalties; Ablynx: Research Funding; Astra Zeneca: Research Funding; Agios: Research Funding. Takahashi:Symbio Pharmaceuticals: Consultancy. Wierda:Gilead Sciences: Research Funding; Juno Therapeutics: Research Funding; KITE pharma: Research Funding; Sunesis: Research Funding; Miragen: Research Funding; Oncternal Therapeutics Inc.: Research Funding; Cyclcel: Research Funding; Acerta Pharma Inc: Research Funding; Pharmacyclics LLC: Research Funding; Genentech: Research Funding; AbbVie: Research Funding; GSK/Novartis: Research Funding; Loxo Oncology Inc.: Research Funding; Janssen: Research Funding; Xencor: Research Funding. Jain:Servier: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; AbbVie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Cellectis: Research Funding; AstraZeneca: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; BMS: Research Funding; ADC Therapeutics: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Verastem: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Pfizer: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen Pharmaceuticals, Inc.: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Genentech: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Adaptive Biotechnologies: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Pharmacyclics, an AbbVie company: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Precision Biosciences: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Incyte: Research Funding. Verstovsek:Pragmatist: Consultancy; Incyte: Research Funding; Roche: Research Funding; NS Pharma: Research Funding; Celgene: Consultancy, Research Funding; Gilead: Research Funding; Promedior: Research Funding; CTI BioPharma Corp: Research Funding; Genetech: Research Funding; Blueprint Medicines Corp: Research Funding; Novartis: Consultancy, Research Funding; Sierra Oncology: Research Funding; Pharma Essentia: Research Funding; Astrazeneca: Research Funding; Ital Pharma: Research Funding; Protaganist Therapeutics: Research Funding; Constellation: Consultancy. Bose:Incyte Corporation: Consultancy, Research Funding, Speakers Bureau; Celgene Corporation: Consultancy, Research Funding; Blueprint Medicine Corporation: Consultancy, Research Funding; Kartos: Consultancy, Research Funding; Constellation: Research Funding; Pfizer: Research Funding; Astellas: Research Funding; NS Pharma: Research Funding; Promedior: Research Funding; CTI BioPharma: Research Funding. O'Brien:Sunesis: Consultancy, Research Funding; Pfizer: Consultancy, Honoraria, Research Funding; Regeneron: Research Funding; AbbVie: Consultancy, Honoraria; Acerta: Research Funding; Alexion: Consultancy; Gilead: Consultancy, Research Funding; Eisai: Consultancy; Pharmacyclics LLC, an AbbVie Company: Consultancy, Research Funding; Amgen: Consultancy; Kite: Research Funding; TG Therapeutics: Consultancy, Research Funding; Vaniam Group LLC: Consultancy; Verastem: Consultancy; Aptose Biosciences, Inc: Consultancy; GlaxoSmithKline: Consultancy; Janssen: Consultancy, Honoraria; Celgene: Consultancy; Astellas: Consultancy. Jabbour:Adaptive: Consultancy, Research Funding; Cyclacel LTD: Research Funding; BMS: Consultancy, Research Funding; Amgen: Consultancy, Research Funding; AbbVie: Consultancy, Research Funding; Pfizer: Consultancy, Research Funding; Takeda: Consultancy, Research Funding.

Background: An international survey we recently conducted indicated that, even today, adults with acute myeloid leukemia (AML) standardly remain hospitalized after completion of induction chemotherapy until resolution of cytopenias due to a high risk of infection and frequent need for transfusions. In contrast, over the last five years at our institution, hospital discharge immediately following completion of induction chemotherapy has become routine after a phase 2 trial evaluating an Early Hospital Discharge (EHD) strategy showed this approach to be safe and cost-effective. On the other hand, EHD is a nearly-universal practice following post-remission or "consolidation" therapy. Here, we sought to compare safety and healthcare resource utilization outcomes for patients who are discharged to the outpatient setting following intensive induction vs. consolidation chemotherapy. Methods: We retrospectively identified all adults aged ≥18 years with newly-diagnosed AML/high-grade myeloid neoplasms (≥10% blasts in peripheral blood/ bone marrow) who started AML-like intensive induction or consolidation chemotherapy ("7+3," high-dose cytarabine [HiDAC], or a regimen of similar/higher intensity) at our institution from 8/1/14 (completion of our phase 2 EHD study) to 7/31/18. EHD was defined as discharge from the hospital within 72 hours of completing chemotherapy (as done in our phase 2 study). Induction therapy was defined as the first course of intensive chemotherapy for untreated disease. Consolidation therapy was defined as intensive therapy if the marrow (and hematologic parameters) prior to starting treatment showed complete remission by standard International Working Group criteria. Patients with relapsed or primary refractory disease were excluded from this analysis. The study period began on the day of initial discharge and ended with count recovery, death, receipt of additional disease-directed therapy, transfer of care, or once 42 days elapsed. We collected baseline demographic and clinical characteristics, logistical information, and treatment regimen. Outcomes of interest including readmission timing/reasons, intensive care unit (ICU) admission, resource utilization (number of lab visits, provider visits, days of IV antimicrobial use, units of transfused red blood cell [RBC] and platelets) and survival. All analyses accounted for correlation between patients because 100 patients were in both the induction and consolidation datasets and 62 patients had more than 1 consolidation cycle in the dataset. Results: We identified 215 induction cycles and 225 consolidation cycles that met our criteria for EHD. As detailed in Table 1, induction EHD patients had worse baseline performance status and higher white blood cell counts than consolidation EHD patients. Consolidation patients spent more time on study (27.8 vs. 24.7 days) and spent a higher proportion of their study time as outpatients (mean of 79% vs. 71% of study time; p Conclusion: Although the early death rate, as would be expected given a baseline sicker population, was higher for EHD patients following induction compared to consolidation chemotherapy, there were no differences between the two groups in requirements for ICU care, laboratory monitoring, or transfusion need in the outpatient setting. This suggests that an EHD strategy following induction therapy may be safely and reasonably implemented at centers with infrastructure supporting EHD following standard consolidation therapy. Disclosures Halpern: Pfizer Pharmaceuticals: Research Funding; Bayer Pharmaceuticals: Research Funding. Othus:Glycomimetics: Other: Data Safety and Monitoring Committee; Celgene: Other: Data Safety and Monitoring Committee. Buckley:CTI BioPharma: Employment, Equity Ownership. Percival:Pfizer Inc.: Research Funding; Nohla Therapeutics: Research Funding; Genentech: Membership on an entity's Board of Directors or advisory committees. Becker:The France Foundation: Honoraria; AbbVie, Amgen, Bristol-Myers Squibb, Glycomimetics, Invivoscribe, JW Pharmaceuticals, Novartis, Trovagene: Research Funding; Accordant Health Services/Caremark: Consultancy. Scott:Novartis: Consultancy; Agios: Consultancy; Incyte: Consultancy; Celgene: Consultancy. Oehler:Pfizer Inc.: Research Funding; Blueprint Medicines: Consultancy; NCCN: Consultancy. Gernsheimer:Fuji film: Consultancy; Bioverativ: Consultancy; Dova pharmaceuticals: Consultancy; Novartis: Honoraria; Cellphire: Consultancy; Amgen: Consultancy, Honoraria; Rigel: Consultancy; Shionogi: Consultancy. Orozco:Actinium Pharmaceuticals: Research Funding. Cassaday:Amgen: Consultancy, Research Funding; Pfizer: Consultancy, Honoraria, Research Funding; Incyte: Research Funding; Kite/Gilead: Research Funding; Merck: Research Funding; Seattle Genetics: Research Funding; Seattle Genetics: Other: Spouse's disclosure: employment, stock and other ownership interests. Shustov:Seattle Genetics, Inc.: Research Funding. Hartley:Pfizer Inc.: Employment, Equity Ownership. Welch:Pfizer Inc: Employment, Equity Ownership. Walter:Agios: Consultancy; Amgen: Consultancy; Amphivena Therapeutics: Consultancy, Equity Ownership; Aptevo Therapeutics: Consultancy, Research Funding; Argenx BVBA: Consultancy; Astellas: Consultancy; BioLineRx: Consultancy; BiVictriX: Consultancy; Boehringer Ingelheim: Consultancy; Boston Biomedical: Consultancy; Covagen: Consultancy; Daiichi Sankyo: Consultancy; Jazz Pharmaceuticals: Consultancy; Kite Pharma: Consultancy; New Link Genetics: Consultancy; Pfizer: Consultancy, Research Funding; Race Oncology: Consultancy; Seattle Genetics: Research Funding.

OBJECTIVE: Patients with core binding factor (CBF) AML generally have a favorable prognosis, but the appropriate intensity of chemotherapy and number of courses are still key points for further exploration by the different leukemic group. Our prospective multicenter clinical study was designed to use high intensity, 4-courses of chemotherapy (backbone of MRC AML 15 protocol) to treat childhood CBF-AML and to observe the feasibility and effectiveness in China. METHODS: Total of 101 children with CBF-AML from 9 centers of south of China were enrolled on the C-HUANAN Children AML 2015 protocol from 2015.1 to 2018.11, accounting for 30.6% of total AML (non-APL) cases. There were 59 boys and 42 girls, aged between 2- 14 years old. The diagnosis of CBF-AML was established by PCR-based detection of RUNX1-RUNX1T1 and CBFβ-MYH11 fusion gene transcripts or by FISH based detection of t(8;21) and inv(16) aberration, respectively. Nine cases were combined with FTL3-ITD. Eleven cases were combined with ASXL1 mutation, and 23 cases were combined with c-KIT mutation. The induction regimen were non-randomized to DAE group and FLAG-IDA group. The induction regimen of DAE group including coures 1 (DAE 3+5+10), course 2 (DAE 3+5+8) . The induction regimen of FLAG-IDA including two courses of FLAG-IDA. Consolidation treatment was same and consisted of 2 courses: 1.HAE or MACE; 2.MidAC. Follow-up observation was then started after 4 courses of treatment. All of patients were followed-up to 06/30/2019, median follow-up time was 25 months. RESULTS: The overall complete remission rate was 93.1% after two courses of induction, 93.8% in the DAE group and 92.8% in the FLAG-IDA group. There was no statistical difference between the two groups. The MRD negative rate ( Conclusion: The childhood CBF-AML accounted for 30.6% of children's newly diagnosed AML in the South China Children's AML Group. The complete remission rate reached to 93.1% by using 2 courses of intensive induction regimen of DAE or FLAG-IDA. Only 2 courses of consolidation chemotherapy were administered. Two years OS and LFS were higher than 80%.There were significant difference in OS of CBF-AML with FLT3-ITD, and RUNX1-RUNX1T1 AML with FLT3-ITD. There were no significant differences in that of LFS. The overall LFS was close to the outcome of the MRC AML 15 protocol, but there was a gap in OS. The main reason was that the most of relapsed patients abandoned treatment. On other hand the treatment related mortality need to be further reduced. Figure Disclosures No relevant conflicts of interest to declare.

Objective: To investigate the long-term prognostic factors of CBFB-MYH11-positive acute myeloid leukemia in low、 intermediate risk patients. Methods:58 CBFB-MYH11-positive patients were analyzed retrospectively in 1525 acute myeloid leukemia patients who were diagnosed in Peking University Institute of Hematology from October 2013 to August 2018, and the clinical feature、induction remission rate and survival were compared. Results: 58 (8%) patients with CBFB-MYH11-positive were found in 1525 newly diagnosed actue myeloid leukemia, 41 males and 17 females were included. The median age was 38(17-66) years , and median follow-up time was 29.8(4.8-74.4)months, 25(43.1%) patients received allogenic hematopoietic stem cell transplantation, in which there were 10 patients with c-kit mutation. According to the NCCN guideline, there were 40 patients in low risk group and 18 patients in intermediate risk group (16 patients with c-kit mutation). The rate of complete remission (CR) in the first induction chemotherapy was 98.3%(57/58), the cumulative remission rate of two cycles was 100%, the relapse rate was 25.9%(15/58), and the mortality rate was 19.0% (11 ≤ 58). After 1 and 2 cycles of consolidation, the level of CBFB-MYH11/ABL decreased to less than 0.18% and 0.094% respectively, which were related to the low recurrence rate. Among the 33 patients who did not undergo allogenic hematopoietic stem cell transplantation after two courses of consolidation, the recurrence rate of patients with CBFB-MYH11/ABL level > 0.1% (n =21) was significantly higher than that of patients with < 0.1% (n = 12) (61.9% VS 0%, P =0. 001), and the relapse-free survival(RFS) (3-year RFS rate 37.6% VS 100%, P =0.005 ) 、event-free survival (EFS)(3-year EFS rate 33. 3% VS 100%, P = 0.004) were significantly decreased. The RFS and EFS were lower than those of patients received allogenic hematopoietic stem cell transplantation (n=25) (3-year RFS rate 31.4% VS 84.6%, P = 0.000; 3-year EFS rate 31.4% VS 76.0%, P =0.004). Conclusions: To the CBFB-MYH11-positive acute myeloid leukemia patients, if the level of CBFB-MYH11/ABL gene presented more than 0.1% at any time after 2 cycles of consolidation, poor prognosis was related to, and allogenic hematopoietic stem cell transplantation could improve the survival. Disclosures No relevant conflicts of interest to declare.

Objective To evaluate the efficacy of consolidation chemotherapy combined with allogeneic natural killer (NK) cell infusion in the treatment of low or intermediate-risk(LIR) AML. Methods 23 cases of LIR AML patients with hematologic complete remission (CR) were enrolled from January 2014 to June 2019 and treated with mIL-21/4-1BBL actived NK cell transfusion combined with consolidation chemotherapy after 3 consolidation courses. Control group were concurrent patients from Department of Hematology and their gender, age, diagnosis, risk stratification of prognosis, CR and the number of courses of consolidate chemotherapy before NK cell transfusion were matched with LIR AML patients. Results A total of 45 times of NK cells were injected into 23 LIR AML patients during 4 to 7 courses of chemotherapy. The median NK cell infusion quantity was 7.5 (6.6~8.64) x 109/L, and the median survival rate of NK cells was 95.4 (93.9~96.9) %. Among them, the median CD3-CD56 + cell number is 5.0(1.4 ~ 6.4) × 109/L, which accounts for 76.8(30.8 ~ 82.9) %; The number of CD3+CD56+ cells was 0.55 (0.24~1.74) x 109/L, accounting for 8.8 (4.9~20.9) %. Before NK cell infusion, the number of patients with positive MRD in the treatment group was 9/23 (39.1%), and the control group was 19/46 (41.3%) (X2=0.03, P=0.862). After NK cell infusion, There was no significant difference in MRD that went from negative to positive between the treatment group and the control group(14.3%vs 22.2%, X2=0.037, P=0.847). In the treatment group, 66.7% (6/9) of the MRD were converted from positive to negative, which was significantly higher than that in the control group10.5% (2/19) (X2=6.811, P=0.009). Morphological recurrence occurred in 1 case of MRD negative in the treatment group and 2 cases of MRD positive in the control group. By the end of the follow-up, the median follow-up was 35 (10~59) months, the number of patients with morphological recurrence in the treatment group was 30.4% (7/23), which is significantly lower than that in the control group (50.2%, 24/46)(X2=2.929, P=0.087),although there was no statistically significant difference between the two groups. There was no significant difference on MRD-negative between the treatment group and the control group(43.5% vs 43.5%, X2=1.045, P=0.307).The 3-year leukemia -free survival were better in the treatment group(65.1±11.1)% than that in the control group (50.0±7.4)%(P=0.047). The 3year overall survival in the treatment and chemotherapy groups were(78.1±10.2)%and (65.8±8.0)%(P=0.212), respectively. Conclusion The consolidation of chemotherapy combined with allogeneic NK cell infusion contributes to the further remission of patients with LMR AML and the reduction of long-term recurrence. Figure Disclosures No relevant conflicts of interest to declare.

Background: Acute megakaryocytic leukemia (AMKL) is a rare subtype of acute myeloid leukemia (AML) with a dismal outcome in children without Down syndrome. Refractory or relapsed disease accounts for treatment failure in most cases. Hematopoietic stem cell transplantation (HSCT) is recommended as post-remission therapy, although some patients have been cured with intensive chemotherapy alone. Genetic and genomic abnormalities are common in AMKL, but their prognostic significance is not known. In this study, we analyzed AMKL using high-throughput sequencing in addition to conventional morphology, immunophenotype, cytogenetic, and molecular (MICM) approaches. Methods: From February 2015 to April 2019, 19 cases of AMKL in non-Down syndrome patients were diagnosed according to conventional methods in our center. All patients, except one, were treated using a low-dose chemotherapy (LDC) regimen (cytarabine 10 mg/m2, subcutaneously every 12 h, 20 doses; mitoxantrone 5 mg/m2 days 1, 3 and 5, and G-CSF 5µ/kg subcutaneous, daily, 10 doses) for induction remission followed by four courses of intensive chemotherapy or hematopoietic stem cell transplantation (HSCT) as post-remission consolidation[1]. Patients were treated with consolidation chemotherapy if parents refused HSCT. High-throughput mutational sequencing of leukemia cells obtained at diagnosis was performed. The average sequencing depth was 500-1000× and analyses were performed using mGATK, SAMTools, SIFT, PolyPhen2, LRT, and MutatioinTaster methods. Results: The average age at diagnosis of AMKL of the nine boys and 10 girls was 19.7 months (7-53 months). Eighty-four percent of the cases were younger than 2 years of age. The 19 patients with AMKL represent 10% of cases diagnosed with AML during the study period. The median initial white blood cell (WBC) count was 13×109/L(2.38-126×109/L)and the average blasts at initial bone marrow (BM) was 54.5% (13-85%). In all cases of AMKL, more than 25% of cells were positive for CD41. Sixty-three percent of patients had recurrent fusion genes, including NUP98-KDM5A, HOXA11-AS/ANGPT1, CBFA2T3-GLIS2, KMT2A-MLLT3, RBM15-MKL1. Also, we identified PICALM-MLL10, TNIP1-CSF1R, NUP98-TAF3, and CBFA2T3-GLIS1 fusion genes which had not been previously reported in AMKL. EVI-1 expression was evaluated in all cases and was overexpressed in two cases. Forty-seven percent of patients showed at least single-gene mutations, including JAK2, MPL, KRAS, NRAS, TP53, NTRK3, MYO16, PDGFB, FLT3, and others. The response rate after remission induction I (IND-I) were 84.2% with 63.1% (12/19) attaining complete remission (CR) and 21.1% (4/19) partial remission (PR). After IND-II, the CR, PR, and no response (NR) rates was 68.4%, 10.5%, and 21.1%, respectively. Four patients (21.1%) were refractory to induction chemotherapy. Seven patients (36.8%) relapsed, three during consolidation chemotherapy courses, and four after transplantation (Table 1). Currently, 75% (6/8) patients who received chemotherapy only for consolidation were alive (median follow-up time 27 months). Eleven patients underwent allo-HSCT, and 8 patients are alive, including 6 cases living without evidence of disease. Four patients relapsed after allo-HSCT, and two of them have died. One additional patient died of transplantation related mortality. The 4-year OS, RFS, and EFS in this cohort were 62.4%±13.9%, 54.1±13.0% and 40.5±11.5%, respectively (Figure 1).Conclusion: Non-Down syndrome AMKL is genetically heterogeneous with recurrent and new fusion genes. Patients treated with LDC for induction followed by intensive chemotherapy or HSCT for consolidation have outcome comparable to those treated with intensive induction regimens. New treatment strategies are needed to improve the outcome of pediatric AMKL. Figure 1 Disclosures No relevant conflicts of interest to declare.

Background: Interferon-𝜶has a world-widely acknowledged anti-tumor activity and immunoregulatory function. Rare of the previous study reported significant efficacy of IFN-𝜶in AML (high, medium and low risk) patients. Although cytotoxic chemotherapy significantly improved the survival of low-risk AML, the reported low-risk AML 5-year OS was only 34-65%.Whether Interferon-𝜶-2b(IFN-𝜶-2b) could reduce recurrence and improve DFS in the maintenance therapy of low-risk AML subtypes has not been verified. The aim of this study was to evaluate the efficacy and safety of IFN-𝜶-2b in the maintenance of low-risk acute myeloid leukemia, in order to provide suggestions for clinical practice. Method: This study retrospectively analyzed 31 patients with low-risk AML who were treated with IFN-𝜶-2b maintenance therapy from March 2015 to March 2018 at the Peking University Institute of Hematology. The control group consisted of 1:1 matched 31 patients with low-risk AML. The pairing factors were age, gender, diagnostic time and subtype, induction and consolidation courses, and minimal residual disease (MRD) at the end of chemotherapy. Both groups of patients were AML patients who underwent 1-2 therapeutic induction chemotherapy for complete hematologic remission (CR) and completed 5-7 courses of consolidation chemotherapy. The interferon group was administered with 3 million U ofIFN-𝜶-2b three times a week; the control group was only observed and followed up after consolidation chemotherapy. We compared the treatment efficacy and prognostic improvement in low-risk AML by comparing MRD, disease-free survival (DFS), event-free survival (EFS), and overall survival (OS). Results: The median age of the 31 patients in the interferon group was 50 (21-67) years. Themolecular biological characteristicsof the interferon group were NPM1+/FLT3-ITD-8 cases; CEBPA double mutation 9 cases; CBFβ-MYH11+/C-KIT-5 cases; and ETO+/C-KIT- 9 cases. The median age of the control group was 44 (26-70) years old, and the molecular biological characteristics were paired with the interferon group. The median follow-up time of the 31 patients with low-risk AML in the interferon group and the control group was 14.5 (4-34) months and 16 (5.5-35) months, respectively. The median duration of treatment in the interferon group was 10(1-24) months. In interferongroup, patients with negative or positive MRD status were 16 and 15, respectively. Whereas, in control group, patients with negative or positive MRD status were 20 and 11, respectively. In interferon group, patients with original MRD, 10/15 (66.67%) showed MRD conversion after the median time of 5 (1-14.5) months IFN-𝜶-2b treatment, while in control group 3/11 (27.3%) of the patients showed MRD negative-positive conversion. There was a statistically significant difference in the rate of MRD conversion between the two groups (X2=3.939, P=0.047). The interferon group significantly decreased the rate of MRD compared with the control group. The conversion rate of the interferon group and the control group was (66.67%) vs (27.3%). In addition, the 2-year EFS of the interferon group was significantly higher than that of the control group (81.6±7.5) % vs (50.0±10.9) %, P=0.041(Figure 1.A). With refer to recurrence, 3 patients had hematologic recurrence in the interferon group, compared with 10 in the control group. Each group has 2 persistent MRD positive patients and MRD level increased more than 2 log-fold. 1 patient in control group had negative MRD converted to positive. The 2-year DFS of the interferon group was significantly higher than that of the control group (81.2±8.8)% vs (56.7±9.9)%, P=0.042 (Figure 1.B). There was no significant difference between the interferon group and the control group at 2 years of OS, which was (91.4±5.8)% vs (78.7±10.8)% (P=0.587) (Figure 1.C).In terms of safety, 24/31 (77.4%) had grade 1-2 fever after IFN-𝜶-2b therapy. 4/31 patients (12.9%) developed grade 3-4 hematologic toxicity, all of which were thrombocytopenia. Conclusion:IFN-𝜶-2b as maintenance therapyfor CR1 patients with low-risk AML significantly improved the rate of MRD conversion compared with patients without it. DFS and EFS were higher than those without it. Patients receiving interferon therapy have a low incidence of adverse reactions. Interferon therapy is safe and well-tolerated. Disclosures No relevant conflicts of interest to declare.

Introduction-About 25% of persons with new-diagnosed acute myeloid leukemia (AML) have normal cytogenetics and no NPM1 or FLT3-ITD mutation. The prognosis and best therapy of these persons is controversial. Methods-We evaluated 809 consecutive newly diagnosed adult with normal cytogenetics and 231 of whom had no NPM1 or FLT3-ITD mutation identified by targeted regional sequencing. 158 achieved a complete remission within 2 cycles of induction therapy and were assigned to 2 different post-remission strategies: (1) 6 courses of consolidation chemotherapy (N=95); or (2) 2-4 courses of consolidation chemotherapy and an allotransplant (N=63). Results-In multi-variable analyses a WBC ≥13·6×10E+9/L, mutated IDH2, not having a bi-allelic CEBPA mutation at diagnosis, a positive measurable residual disease (MRD)-test during consolidation and not receiving an allotransplant were independently associated with a higher cumulative incidence of relapse (CIR) and worse event-free survival (EFS). Amongst subjects with IDH2 mutations, non-bi-allelic CEBPA mutations or a positive MRD-test, subjects receiving an allotransplant had a lower 5-year CIR (16% [95% confidence interval, 6, 26%]; vs. 83% [72, 95%]; hazard ratio, HR=8·77 [4·05, 13·49]; P < 0·001) and better 5-year EFS (74% [60, 88%] vs. 15% [5, 25%]; HR=0·16 [0·09, 0·29]; P < 0·001). In contrast, in subjects with none of these adverse predictive variables there was no difference in CIR and EFS between those receiving an allotransplant and those who did not. Conclusions-Our data suggest a strategy to identify which persons with AML with normal cytogenetics and no NPM1 or FLT3-ITD mutation benefit from an allotransplant. Trial Registration: Registered in the www.clinicaltrials.gov, NCT01455272 and NCT02185261. Keywords: Acute myeloid leukemia, mutations, prognosis, targeted regional sequencing, measurable residual disease, risk stratification. *Correspondence Profs. Guo-Rui Ruan and Xiao-Jun Huang Peking University Peoples Hospital and Institute of Hematology No.11 Xi-Zhi-Men South Street, Beijing 100044, China T 86-10-88324672 F 86-10-88324672 Disclosures No relevant conflicts of interest to declare.

Introduction: Although induction chemotherapy results in a complete remission (CR) in ~70% of newly diagnosed AML patients, post-remission therapies are needed to eliminate minimal residual disease (MRD) and prevent relapse. Consolidation chemotherapy, either as definitive therapy or bridge to bone marrow transplantation (BMT), is currently the most common form of post-remission therapy. Yet, our understanding of its impact on MRD remains limited. In this study, we investigated the effects of consolidation chemotherapy on molecular MRD (mMRD) burden using ultra-deep next generation sequencing (NGS) and correlated treatment response with disease characteristics and survival outcomes in AML patients. Patients and Methods: 91 newly diagnosed AML patients who achieved CR following standard induction chemotherapy were evaluated. Targeted conventional NGS using a 54-gene panel was performed on whole blood (PB) or bone marrow samples collected at diagnosis. PB samples were collected during remission at two consecutive time points (T1 and T2), before and after 1 (n=79) or 2 (n=12) cycles of consolidation chemotherapy, for each patient. To detect mMRD, we used a custom 37-gene hybrid-capture panel and error-corrected NGS based on the duplex sequencing approach with a variant allele frequency (VAF) detection limit of ~1x10-4. For 10 patients, we also performed duplex sequencing analysis on their relapsed samples. Results: NGS of the diagnostic samples identified a total of 298 putative oncogenic mutations in 92% (n=84) of the 91 patients. Ninety percent of these mutations (n=267) were trackable by the custom hybrid-capture panel. Duplex sequencing detected persistence of 56% (n=149) of the trackable mutations in T1 samples; 34% (n=50) of which were clonal hematopoiesis-associated DTA mutations (those involving DNMT3A, TET2, or ASXL1), and the remaining 66% (n=99) were non-DTA mutations. Analysis of T2 samples showed that consolidation chemotherapy reduced the VAF of non-DTA mutations by a median of 73% and cleared 27% (n=27) of them at T2. In contrast, the burden of DTA mutations increased by 0.5% (P < 0.0001 by Mann-Whitney test), and only 2% (n=1) of the mutations was cleared (P = 0.0001 by Fisher's exact test). These findings are consistent with prior studies demonstrating that non-DTA mutations are more reliable markers of leukemic burden than DTA mutations. To study the impact of consolidation chemotherapy at the level of individual patients, the mean VAF of all persistent non-DTA mutations was calculated for each sample and used as a composite measure of mMRD burden (henceforth referred to as "cmMRD"). Analysis of the 10 patients with relapsed samples showed that cmMRD levels tracked well with achievement of remission and disease progression (Fig. 1). In the subset of patients with persistent non-DTA mutations at T1 (n=61), consolidation chemotherapy decreased cmMRD levels by a median of 36% at T2. However, we observed high interpatient variability (Fig. 2); 36% (n=22) of the patients experienced an increase in cmMRD burden after consolidation chemotherapy, and 36% (n=22) had less than a 1 log reduction. Only 28% (n=17) of the patients achieved a log reduction of greater than 1. The likelihood and magnitude of cmMRD response were significantly associated with cytogenetic risk (P = 0.026 by 3x3 Chi-square test; Fig. 3). The proportion of patients with favorable, intermediate, and poor-risk cytogenetics who experienced cmMRD expansion was 17%, 27%, and 71%, respectively. Consistent with these findings, a suboptimal response (defined as cmMRD ratio [T2/T1] > 0.4) was associated with inferior overall survival (HR = 3.29, P = 0.007 by log-rank test; Fig. 4). Conclusions: Our analysis showed that mMRD response to consolidation chemotherapy was highly variable among patients. Although consolidation chemotherapy was effective in deepening the remission for a subset of patients, it failed to lower MRD levels for a substantial proportion of patients, especially those with poor risk cytogenetics. These findings challenge the practice of using consolidation chemotherapy to achieve a deeper remission prior to BMT for high-risk patients and indicate that the opposite outcome may occur instead. NGS-based monitoring of mMRD can potentially be used to distinguish between patients who can remain on consolidation chemotherapy as definitive therapy and those who require a switch in post-remission therapy. Disclosures Gupta: Sierra Oncology: Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Incyte: Honoraria, Research Funding. Maze:Pfizer Inc: Consultancy; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees. McNamara:Novartis Pharmaceutical Canada Inc.: Consultancy. Minden:Trillium Therapetuics: Other: licensing agreement. Schimmer:Medivir Pharmaceuticals: Research Funding; Jazz Pharmaceuticals: Consultancy; Novartis Pharmaceuticals: Consultancy; Otsuka Pharmaceuticals: Consultancy. Schuh:Pfizer: Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees; Jazz: Honoraria, Membership on an entity's Board of Directors or advisory committees; Agios: Honoraria; Astellas: Honoraria, Membership on an entity's Board of Directors or advisory committees; Teva Canada Innovation: Honoraria, Membership on an entity's Board of Directors or advisory committees; AbbVie: Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees. Yee:Novartis, Pfizer: Honoraria, Membership on an entity's Board of Directors or advisory committees; Astellas, Celgene, Otsuka, Shire, Takeda: Membership on an entity's Board of Directors or advisory committees; Agensys, Astex, Hoffman La Roche, MedImmune, Merck, Millenium, Roche/Genentech: Research Funding. Bratman:SVB: Other: is co-inventor of a patent relating to circulating tumor DNA detection technology, which has been licensed to Roche Molecular Diagnostics.. Chan:Agios: Honoraria; AbbVie Pharmaceuticals: Research Funding; Celgene: Honoraria, Research Funding.

High-risk acute myelogenous leukemia (AML) constitutes a distinct subset of disease based on clinical and biological characteristics and comprises a significant percentage of all cases of adult AML. Biologic features such as distinct clonal cytogenetic and molecular abnormalities identify a subgroup of AML patients characterized by poor response to induction chemotherapy and poor long-term survival after treatment with consolidation chemotherapy. Clinical variables that predict for poor response include AML relapsed after less than 1 year of remission and AML characterized by resistance to conventional agents. We review here our understanding of the defining biologic subtypes of AML and discuss how adequate initial evaluation can be used to inform the choice of treatment. By defining high-risk biologic and clinical variables, a strong case can be made for treating patients with investigational agents, with treatment directed at distinct cytogenetic or molecular abnormalities. Allogeneic transplantation is the only form of therapy available outside of the setting of a clinical trial that may offer a chance for long-term survival for patients with high-risk AML.

This randomized phase 3 clinical trial evaluated the potential benefit of the addition of gemtuzumab ozogamicin (GO) to standard induction and postconsolidation therapy in patients with acute myeloid leukemia. Patients were randomly assigned to receive daunorubicin (45 mg/m2 per day on days 1, 2, and 3), cytarabine (100 mg/m2 per day by continuous infusion on days 1–7), and GO (6 mg/m2 on day 4; DA+GO) vs standard induction therapy with daunorubicin (60 mg/m2 per day on days 1, 2, and 3) and cytarabine alone (DA). Patients who achieved complete remission (CR) received 3 courses of high-dose cytarabine. Those remaining in CR after consolidation were randomly assigned to receive either no additional therapy or 3 doses of GO (5 mg/m2 every 28 days). From August 2004 until August 2009, 637 patients were registered for induction. The CR rate was 69% for DA+GO and 70% for DA (P = .59). Among those who achieved a CR, the 5-year relapse-free survival rate was 43% in the DA+GO group and 42% in the DA group (P = .40). The 5-year overall survival rate was 46% in the DA+GO group and 50% in the DA group (P = .85). One hundred seventy-four patients in CR after consolidation underwent the postconsolidation randomization. Disease-free survival was not improved with postconsolidation GO (HR, 1.48; P = .97). In this study, the addition of GO to induction or postconsolidation therapy failed to show improvement in CR rate, disease-free survival, or overall survival. This trial is registered with www.clinicaltrials.gov as #NCT00085709.

There are no data on the role of postconsolidation therapy with gemtuzumab ozogamicin (GO; Mylotarg) in children with acute myeloid leukemia (AML). The NOPHO-AML 2004 protocol studied postconsolidation randomization to GO or no further therapy. GO was administered at 5 mg/m2 and repeated after 3 weeks. We randomized 120 patients; 59 to receive GO. Survival was analyzed on an intention-to-treat basis. The median follow-up for patients who were alive was 4.2 years. Children who received GO showed modest elevation of transaminase and bilirubin without signs of veno-occlusive disease. Severe neutropenia followed 95% and febrile neutropenia 40% of the GO courses. Only a moderate decline in platelet count and a minor decrease in hemoglobin occurred. Relapse occurred in 24 and 25 of those randomized to GO or no further therapy. The median time to relapse was 16 months versus 10 months (nonsignificant). The 5-year event-free survival and overall survival was 55% versus 51% and 74% versus 80% in those randomized to receive GO or no further therapy, respectively. Results were similar in all subgroups. In conclusion, GO therapy postconsolidation as given in this trial was well tolerated, showed a nonsignificant delay in time to relapse, but did not change the rate of relapse or survival (clinicaltrials.gov identifier NCT00476541).

We conducted a prospective randomized study to assess the optimal postremission therapy for adult acute myeloid leukemia in patients younger than 65 years in the first complete remission. A total of 781 patients in complete remission were randomly assigned to receive consolidation chemotherapy of either 3 courses of high-dose cytarabine (HiDAC, 2 g/m2 twice daily for 5 days) alone or 4 courses of conventional standard-dose multiagent chemotherapy (CT) established in the previous JALSG AML97 study. Five-year disease-free survival was 43% for the HiDAC group and 39% for the multiagent CT group (P = .724), and 5-year overall survival was 58% and 56%, respectively (P = .954). Among the favorable cytogenetic risk group (n = 218), 5-year disease-free survival was 57% for HiDAC and 39% for multiagent CT (P = .050), and 5-year overall survival was 75% and 66%, respectively (P = .174). In the HiDAC group, the nadir of leukocyte counts was lower, and the duration of leukocyte less than 1.0 × 109/L longer, and the frequency of documented infections higher. The present study demonstrated that the multiagent CT regimen is as effective as our HiDAC regimen for consolidation. Our HiDAC regimen resulted in a beneficial effect on disease-free survival only in the favorable cytogenetic leukemia group. This trial was registered at www.umin.ac.jp/ctr/ as #C000000157.

Background: Granulocyte colony stimulating factor (G-CSF) to prevent neutropenic fever is a well-accepted standard of care to minimize the risk of neutropenic fever during consolidation chemotherapy for acute myeloid leukemia (AML). Although prospective, randomized clinical trials of filgrastim versus depot pegfilgrastim demonstrated biologic equivalency, retrospective studies in patients with solid tumors suggest the use of pegfilgrastim results in reduced rates of admission for neutropenic fever. Patients undergoing AML consolidation may be at higher risk for admission, as with solid tumors. Biosimilars for filgrastim (filgrastim-sndz and tbo-filgrastim) and pegfilgrastim (pegfilgrastim-jmdb) are creating market forces that may make daily administered agents an attractive alternative to pegfilgrastim, and therefore additional observational studies to clarify of the safety of daily administered G-CSF vs depot injections. We hypothesize that the use filgrastim over pegfilgrastim may result in higher hospital admission rates in AML patients undergoing consolidation chemotherapy outside the setting of prospective trials. Methods: Patient charts from the year 2004 through early 2017 diagnosed with AML at the Seidman Cancer Center of University Hospitals Cleveland Medical Center (UHCMC) were reviewed as a retrospective cohort study. Patient were included who received at least one cycle of high dose cytarabine during 1st complete remission, and received filgrastim or pegfilgrastim were considered available for analysis. Individual cycles of chemotherapy were assessed for potential adverse outcomes with the use of different forms of GCSF. The primary outcome of interest is hospitalization during consolidation chemotherapy. The incidence of hospitalization was analyzed using longitudinal logistic regression with generalized estimating equations for statistical inference assuming exchangeable variance-covariance structure of multiple hospitalizations from the same patients. Results 436 patient charts were reviewed identifying 165 patients receiving at least one cycle of HiDAC chemotherapy. Of these, 156 patients received either filgrastim or pegfilgrastim, representing 256 cycles of high dose cytarabine chemotherapy supported with GCSF. Patients receiving filgrastims vs pegfilgrastim differed in the number of HiDAC cycles received (1.64 vs 1.97, p = 0.046), the distribution of favorable risk AML (11.9% vs 32.7%, p = 0.035). Groups did not differ based on age, sex, race, initial response to therapy, and proportion of secondary AML. After controlling the effects of age, sex, race and initial clinical response, treatment (filgrastim vs. pegfilgrastim) was significantly associated with hospitalization during consolidation therapy (p = 0.005). Specifically, the odds of having hospitalization for patients treated with Filgrastim is estimated to be 2.31 times the odds of having hospitalization for patients treated Pegfilgrastim with 95% CI (1.28, 4.17). Also, the estimated probability of having hospitalization for patients treated with filgrastim was 0.59 (95% CI: 0.43- 0.73) vs. 0.38 (95% CI: 0.27 - 0.51) for patients treated with pegfilgrastim. Conclusions: The use of filgrastim was found to be statistically significantly associated with and increased risk of hospitalization. Disclosures Caimi: Kite Pharma: Other: Advisory Board Participation; Celgene: Speakers Bureau; Genentech: Other: Advisory Board PArticipation, Research Funding; Kite Pharma: Other: Advisory Board Participation. Little:PCORI: Research Funding; Hemex: Patents & Royalties: Patent, no honoraria; Doris Duke Charitable Foundations: Research Funding; NHLBI: Research Funding. Malek:Sanofi: Consultancy, Speakers Bureau; Celgene: Consultancy, Speakers Bureau; Janssen: Consultancy, Speakers Bureau; Amgen: Consultancy, Speakers Bureau; Takeda: Consultancy, Speakers Bureau.

Background: Although acute myeloid leukemia (AML) occurs most commonly in adults ≥60 years, the treatment of AML in older patients remains a significant challenge due to both, more aggressive disease biology as well as patient-related risk factors that limit tolerance of intensive chemotherapy. Several studies demonstrated improved survival for older patients receiving intensive induction chemotherapy. Therefore intensive chemotherapy, as long as patient fitness allows, is aimed. Defining the subset of patients that is eligible or "fit" for intensive chemotherapy involves a great deal of subjectivity. Criteria yet have to be standardized across or within institutions. Aim: The aim of the present study was to investigate the power of three validation scores in assessing patient fitness at diagnosis in parallel to physician evaluation. Further patient outcome according the respective assessment was compared. Methods: A total of 130 clinically and molecularly well characterized consecutive elderly (≥60 years) patients with newly diagnosed AML were treated from 2012 to 2018 according to age, performance status and co-morbidities in a single hematology center. Initial haematologist evaluation followed by discussion of the patient case in an interdisciplinary board led to decision of therapy intensity of each patient. In parallel, independently from the medical board decision, three scores were performed: i) a local geriatric G8 screening tool, consisting of seven items from the Mini Nutritional Assessment (MNA) questionnaire and age, ii) the Sorror Index used for hematopoietic stem cell transplantation (HSCT) evaluation as well as iii) the AML score proposed by the German Acute Myeloid Leukemia Cooperative Group, predicting the probability of complete remission (CR) and early death (ED). Therapy response was defined according to ELN criteria. Overall survival from diagnosis was compared between groups using the Cox model. Results: Median age was 71,2 (range: 60-86) years. A total of 75 (57,7%) patients were evaluated "fit" by the medical board and treated by intensive chemotherapy ("7+3" regimen), whereas 41 patients (31,5%) underwent semi-intensive therapy (based on hypomethylating agents or low-dose Cytarabine s.c.) and 14 patients (10,7%) received best supportive care. Fifty patients (38,5%) achieved a complete remission after induction chemotherapy, could follow consolidation chemotherapy and ten of them underwent allogeneic HSCT. Sixty-four (49,2%) were non responders and 16 patients (12,3%) died during the first cycle. Overall, the median survival time was 11,2 months (95% CI 7,9-17,8). Primary physician care evaluation was able to define a "fit" from an "unfit" patient in a statistically significantly way. Median survival time from the "fit" patients was 17,6 months (95%CI 9-28,9) compared to the "unfit" evaluated patients with 3,6 months (95%CI 1,8-8,8), p Conclusion: In conclusion, the frailty scores G8, Sorror Index and the AML Score, that have been applied to elderly patients at AML diagnosis seem to discriminate patients quite well in terms of overall survival in this single centre patient cohort and may represent objective instruments for the haematologist in the validation of the fitness of the elderly AML patients for intensive chemotherpy. In order to validate the discrimination ability arising from the performed analysis, a multi-centre study is planned. Disclosures Vitolo: Gilead: Speakers Bureau; Roche: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Janssen: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Takeda: Speakers Bureau; Sandoz: Speakers Bureau.

Introduction: Mainstay of chemotherapy in acute myeloid leukemia (AML) is induction with a goal to achieve morphological complete remission (CR) as evident by less than 5% blasts. Post remission strategies then focus on either consolidation chemotherapy or allogeneic bone marrow transplantation (aBMT). However, not all patients by this remission criterion achieve long term remission and a subset of patients' relapse. This relapse originates from further expansion chemoresistant clones. Detection of minimal residual disease (MRD) following chemotherapy, early in the course of treatment, is highly predictive of outcome and offers a window of opportunity to intensify treatment and prevent relapse as seen in ALL. Here, we describe assessment of immunophenotypic MRD using a 10-colour two tube assay and a combination of difference from normal and leukemia associated immunophenotype (LAIP) approach in patients of adult AML. Methods: We accrued 310 patients of adult (>18 years) AML, other than with t(15;17), over a 66-month period (1st July 2012- 31st December 2017) after obtaining informed consent. All patients received standard induction chemotherapy. MRD testing was done post induction and after first consolidation with high dose cytarabine. Patients accrued from 1st July 2012 to 28th February 2015 (85 patients) were processed using a three tube 8 colour MRD assay. Subsequently samples of 225 patients were processed using a two tube 10 colour MRD assay. Identical panel was used for diagnostic sample, post induction and post consolidation. 500,000 events were acquired per tube with the 3-tube assay and 1.6 million events per tube obtained per tube with the 2 tube, 10 colour assay. Analysis of MRD was done using Kaluza 1.3 by a combination of difference from normal approach that focused on the development of Myeloid progenitors to mature cells and LAIP approaches. Cytogenetic studies by conventional karyotyping and FISH was done as per NCCN version 2 2014 recommendations. Patients were classified into favorable, intermediate and poor cytogenetic risk. The presence of FLT3-ITD, NPM1 and CEBPA mutations were detected by a fragment length analysis-based assay. Overall survival (OS) was calculated from date of diagnosis to time of last follow up or death. Relapse free survival (RFS) was calculated from date of CR till time to relapse or death or last follow up if in CR. Results of the MRD assays, cytogenetic and molecular risk groups were analyzed for their impact on OS and RFS using log rank test. Results: The median age of entire cohort was 33 years (M : F = 1.6 : 1). Based on cytogenetics, 35.1% were classified as favorable risk whereas 52.5% and 12.2% were intermediate and poor risk respectively. FLT3-ITD, NPM1 and CEBPA mutations were detected in 21.9%, 29.0% and 7.7% of patients respectively. Post induction MRD was assessed in 298 patients of which 114 (38.3%) had detectable residual disease (range 0.004-22.6%, median:0.9%). Post consolidation MRD was assessed in 186 patients of which 49 (26.4%) were MRD positive (range 0.002-19.8%, median: 0.37%).The 3 year OS, RFS and median RFS of the entire cohort was 59.0%, 44.8% and 18.7 months respectively. Poor risk cytogenetics as expected was predictive of inferior OS (median OS = 14.6 months vs not reached, p=0.05) as well as RFS (median RFS = 9.3 months vs 18.6 months, p=0.003 respectively). FLT3, NPM1 and CEBPA mutations were not informative as predictors of outcome.The presence of MRD at post induction time point predicted an inferior OS [(p=0.08), HR:1.53; 95% CI (0.93-2.51)] & RFS [(p=0.0002), HR:2.14; 95% CI (1.4-3.3)] as compared to the MRD negative group. Similarly, patients harboring MRD at the end of consolidation had an inferior OS [(p=0.04), HR:1.83; 95% CI (0.94-3.6)] & RFS [(p=0.02), HR:1.79; 95% CI (1.04-3.09)] as compared to the MRD negative group. On multivariate analysis post induction FCM MRD emerged as the most important independent prognostic factor predictive of inferior outcome for RFS [(p=0.01); HR:2.14; 95% CI (1.17 - 3.4)] followed by poor cytogenetic risk [(p=0.05); HR:1.8; 95% CI (1.0 to 3.26)]. Conclusion: Our data demonstrates that MRD by flow cytometry at end of induction as well as consolidation are important prognostic factors together with known factors such as high risk cytogenetics. AML MRD is a very useful guide for post remission strategies in AML and should be incorporated into routine treatment algorithms. Figure. Figure. Disclosures No relevant conflicts of interest to declare.

Introduction: The randomized phase 3 ALFA-0701 study demonstrated improved outcomes with the addition of gemtuzumab ozogamicin (GO) to standard 7+3 chemotherapy in patients with de novo acute myeloid leukemia (AML; Castaigne et al, Lancet 2012). 85 of 271 patients in the study received hematopoietic stem cell transplantation (HSCT) at any time during study. Here we describe transplant characteristics and compare survival and veno-occlusive disease (VOD) outcomes in these patients. Methods: Patients aged 50-70 years with de novo AML who received standard chemotherapy treatment (daunorubicin and cytarabine) with the addition of GO (GO arm) or alone (control arm) and underwent HSCT as part of the open-label, randomized phase 3 ALFA-0701 study were included in this analysis. Patients who experienced complete remission could be considered for allogeneic HSCT according to performance status, age, the existence or not of a related donor, and cytogenetic and molecular risk categories. Allogeneic HSCT was considered for patients in the European LeukemiaNet (ELN) intermediate 2 or adverse risk group. The type of pre-transplant conditioning regimen was left to the discretion of the transplant center. An interval of 2 months between the last dose of GO and HSCT was recommended. Post-transplant survival was defined as the time from HSCT to death due to any cause. Data on VOD events were extensively collected from screening up to the patient's death or the data collection cutoff date (November 1, 2013), whichever occurred first. Results: A total of 32 patients in the GO arm and 53 patients in the control arm underwent HSCT (Table). All patients received allogeneic HSCT except for 1 patient in the control arm who received autologous HSCT. In the GO arm, 17 patients received HSCT in first remission, 2 after induction failure, and 13 after relapse. In the control arm, 22 patients received HSCT in first remission, 9 after induction failure, and 22 after relapse. Median (range) age was 60 (51-67) years in the GO arm and 59 (50-69) years in the control arm, and 47% and 45% were male, respectively. The distribution of ELN risk classification was similar for the GO vs control arm, respectively (favorable/intermediate: 63% vs 72%; adverse: 28% vs 25%). Only 1 patient in the control arm who received GO as follow-up therapy received transplant As of April 30, 2013, 18 (56%) patients in the GO arm and 28 (53%) in the control arm had died: 7 and 16 of these deaths were attributed to disease progression/relapse, and 4 and 7 were attributed to graft versus host disease, respectively. Median post-transplant survival was 21.4 months in the GO arm vs 17.1 months in the control arm, with 3-year survival probability (95% confidence interval [CI]) of 39% (22-57) vs 45% (31-58), respectively (hazard ratio [HR]=0.97). Median post-transplant survival was not yet reached in the GO arm vs 19.2 months in the control arm for patients who received HSCT while in first remission, with 3-year survival probability (95% CI) of 53% (28-73) vs 46% (24-64), respectively (HR=0.71; Figure). In patients who received HSCT after relapse or induction failure, median post-transplant survival was 14.5 vs 10.5 months in the GO vs control arm, with 3-year survival probability (95% CI) of 21% (4-48) vs 44% (26-61), respectively (HR=1.42). In all, 3 patients in the GO arm and 2 in the control arm (both of whom received GO as follow-up therapy) developed VOD; 3 of these cases (2 in GO arm; 1 in control arm) occurred post-transplant. All but 1 patient fully recovered. Conclusions: Similar post-transplant outcomes were observed in patients with AML treated with standard chemotherapy with and without GO. The use of GO was not associated with an excess of VOD events after HSCT. The results suggest that the administration of GO as part of induction and consolidation chemotherapy for AML does not induce excess post-transplant mortality and thus does not preclude the use of transplant as consolidation treatment following induction or salvage treatment. Disclosures Benner: Pfizer: Employment, Equity Ownership. Vandendries:Pfizer Inc: Employment, Equity Ownership. Gogat:Pfizer Inc: Employment, Equity Ownership. Castaigne:Pfizer: Honoraria, Research Funding.

Introduction Core-binding factor (CBF) acute myeloid leukemias (AML) are characterized by the chromosomal abnormalities t(8;21) or inv(16)/t(16;16) and their fusion proteins RUNX1/RUNX1T1 and CBFB-MYH11, respectively. Despite their relatively favorable prognosis, it has been reported that up to 45% of patients with CBF-AML relapse. Current guidelines recommend monitoring the peripheral blood (PB) or bone marrow (BM) for molecular evidence of residual disease (RD) every 3 months for 2 years following remission. By monitoring patients for rising molecular transcripts, those at risk of impending relapse can be identified and treated prior to the emergence of overt disease. However, the relapse kinetics of CBF-AML are poorly-understood, and it is unknown if serial RD monitoring can detect molecular relapses with sufficient lead-time to intervene and prevent morphologic relapse. Methods After local REB approval, we identified patients with CBF-AML treated at the Princess Margaret Cancer Centre in Toronto, Canada between 2000 and 2017. Patients underwent induction and consolidation chemotherapy according to standard protocols followed by RD monitoring with polymerase chain reaction (qPCR) of RUNX1/RUNX1T1 or CBFB-MYH11 transcripts in a CAP/CLIA certified lab every 3 months for a median of 1.2 years (range 0-5.3). RD assessment was performed on BM aspirates, but PB could be tested in patients who could not tolerate repeat BM aspirates. Morphologic relapse was defined as emergence of >5% blasts in the PB or BM, and molecular relapse as a positive transcript PCR (if previous PCR measurements were undetectable) or an increase by 1 log (if previous PCR measurements were detectable) on 2 successive samples without morphologic relapse. Rapid relapse was defined as Results We included 114 patients with CBF-AML. Median age was 46.5 years (range 18-79). t(8;21) was present in 59% and inv(16)/t(16;16) in 41% of patients. All patients achieved remission with 7+3 induction chemotherapy. Over a median follow-up time of 3.7 years (range 0.2-14.3), RD measurements were performed a mean of 5 times per patient with mean sampling interval of 103±54 days. Remission was maintained in 71 (62%) patients but 43 (38%) developed morphological (n=34) or isolated molecular relapse (n=9), with median time to relapse of 4.4 months (range 1.4-31.4). Patients with relapsed disease were significantly less likely to have achieved ≥3 log reduction in RUNX1/RUNX1T1 or CBFB-MYH11 BM transcripts at the end of consolidation chemotherapy compared to patients who remained in remission (75% vs 90%, p=0.046). Of the 43 patients who relapsed, the majority (74.4%, n=32) had rapid relapse kinetics. Of these 43 patients, 25 received reinduction chemotherapy with achievement of CR2, 6 had refractory disease or death, 1 was lost to follow-up, and 17 went on to receive allotransplantation. RD monitoring enabled timely detection of impending relapse and permitted intervention prior to morphologic relapse in only 11 patients (25.6%). Among these 11 patients with slower relapse kinetics, 6 received reinduction chemotherapy with achievement of CR2, 2 received reinduction chemotherapy with refractory disease, and 8 went on to receive allotransplantation. Median overall survival was 20 months (range 3-128) for patients with rapid relapse kinetics and 28 months (range 14-166) for patients with slow relapse kinetics (p=0.02). Clinical features, BM vs PB RD measurements, additional molecular mutations, and cytogenetic abnormalities did not distinguish patients with rapid vs slow relapse kinetics. Conclusions Current guidelines recommend molecular RD monitoring every 3 months for CBF-AML. However, in the majority of patients who relapsed at our institution, RD monitoring every 3 months provided insufficient lead-time to identify molecular relapses prior to morphologic relapse. Further research is warranted to identify the patients with CBF at the highest risk of relapse and the best strategies to monitor these patients over time. Disclosures Gupta: Novartis: Consultancy, Honoraria, Research Funding; Incyte: Research Funding. Maze:Novartis: Consultancy, Honoraria. Schuh:Celgene: Consultancy; Novartis: Consultancy; Pfizer: Consultancy; Jazz: Consultancy; Amgen Inc.: Consultancy; Shire: Consultancy; Teva: Consultancy; Otsuka: Consultancy. Yee:Celgene, Novartis, Otsuka: Membership on an entity's Board of Directors or advisory committees; Agensys, Astex, GSK, Onconova, Genentech/Roche: Research Funding. Schimmer:Otsuka Pharmaceuticals: Consultancy; Jazz Pharmaceuticals: Consultancy; Medivir AB: Research Funding; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees.

Objective The aim of this study was to evaluate the effect of super high-dose cytarabine (SHDAC), a regimen first created by the author, on the five-year overall survival (OS) and event-free survival (EFS) of children with AML. Methods From July 2001 to April 2016, a total of 25 pediatric patients with newly diagnosed AML (exclueding secondary AML、APL and Down Syndrome AML) were enrolled. Patients received consolidate chemotherapy with the same regimen of high-dose cytarabine (3g/m2 every 12 hours by continuous infusion for 6 days) after remission induction chemotherapy. Then phase II consolidation therapy (also known as early intensive treatment) was performed according to the regimen of high-dose cytarabine (3g/m2 every 12 hours on days 1, 3, and 5 for four cycles, a total of 108g/m2) in 16 cases, while the other 9 cases received the treatment with another regimen (H3A7, M3A7 and VP16 combined with cytarabine alternately at intervals ranging from 2 to 6 months). The total treatment course spanned about three years, with regular post-treatment follow-up tracking for more than five years. Results Originally 26 cases were enrolled, but 1 case was not relieved after two courses of treatment and quitted therapy, so only 25 cases were enrolled finally. The total remission rate was 96%. There were 12 cases (48%) achieving complete remission within one course, 12 cases (48%) within two consecutive remission course and one case (48%) ,only one case(4%) achieving complete remission within with in five courses. The five-year OS and EFS of these 25 AML patients in this study were 77±0.98% and 77±1.22% respectively. Four patients (16%) died (1 treatment-related (4%), 3 relapse (12%) including 3 marrow relapse and 1 combined with testicular relapse). The average relapse time was 29.6 months and the median time was 14.8 months. Conclusion The application of super high-dose cytarabine (a total of 108g/m2 cytarabine, with a regimen of 3g/m2 every 12 hours by continuous infusion for 6 days as consolidation chemotherapy and 3g/m2 every 12 hours on days 1, 3, and 5 for four cycles as the early intensive treatment) is clinically safe and effective, with minimal hospitalization expense index (HEI). For patients with financial difficulties, especially those in developing countries, super high-dose cytarabine shows landslide advantages and practicality. Therefore, there should be more collaborative clinical applications as well as research upon related mechanisms. Disclosures No relevant conflicts of interest to declare.

Introduction: Patients with acute myeloid leukemia (AML) undergoing consolidation chemotherapy with high dose cytarabine (HiDAC) are often placed on prophylactic antimicrobials. This practice is largely based on the defined benefit of antimicrobial prophylaxis for AML patients during induction chemotherapy. Recent concerns regarding antimicrobial prophylaxis include increased risk of Clostridium difficile colitis, antimicrobial toxicities, and the potential for fostering multidrug-resistant pathogens. These emerging concerns coupled with the relatively shorter duration of neutropenia for AML patients with consolidative chemotherapy raised the question of whether antimicrobial prophylaxis in this setting is necessary. Therefore we examined the role of antimicrobial prophylaxis in HiDAC consolidation within our institution. Methods: This retrospective review included all adult patients who received HiDAC consolidation chemotherapy between January 2007 and March 2018. HiDAC was defined as a dose of 1g/m2 or greater. In patients receiving more than one cycle of HiDAC, data from each cycle was included. Patients prescribed antibiotics, antiviral medications, or antifungal medications at the time of discharge following HiDAC were considered to have received prophylactic antimicrobials. Several baseline patient characteristics were documented including age, sex, Charlson Comorbidity Index, and ECOG PS. The primary endpoint was incidence of febrile neutropenia (FN), while secondary endpoints consisted of hospitalizations for any cause as well as incidence of bacteremia, invasive fungal infection, Clostridium difficile colitis, and death from infection. Patients admitted within one month following HiDAC consolidation were considered to have been hospitalized following therapy. Data was then analyzed based on whether or not patients received antibiotic and antimicrobial prophylaxis. Patients less than 60 and 60 years of age an older where also analyzed separately regarding the use of prophylactic antibiotics to determine if older patients benefited from antibiotic prophylaxis. Results: One hundred twenty patients met inclusion criteria, and data from two hundred thirty-three cycles of HiDAC was analyzed. No significant demographic differences were detected amongst patients who did and did not receive antimicrobial prophylaxis (Table 1). There was no difference in incidence of FN or the number of hospitalizations for each cycle of HiDAC consolidation amongst the prophylaxis and no prophylaxis cohorts. The only statistically significant difference between groups was that in cycle 2 the mean length of hospital stay following HiDAC consolidation was less (p=0.02) in patients prescribed prophylactic antimicrobials. The rates of bacteremia and Clostridium difficile colitis were also similar across both groups in all three cycles of HiDAC consolidation (Table 1). In the setting of HiDAC consolidation, only one patient was found to have an invasive fungal infection and zero patients died as a result of infection. When only antibiotic prophylaxis was analyzed there was likewise no difference in the rates of FN across all 3 cycles of HiDAC nor was there a difference in incidence of FN for patients < 60 and patients ≥ 60 (Figure 1). Furthermore, there was no difference in demographics or other outcomes amongst the antibiotic prophylaxis and no prophylaxis cohorts (data not shown). Discussion: Neither antibiotic nor antimicrobial prophylaxis during consolidation chemotherapy with HiDAC reduced the incidence of FN or frequency of hospitalizations. Additionally, there was no difference in the rates of bacteremia, Clostridium difficile colitis, or invasive fungal infections between the two groups. Importantly, no patients in either cohort died from infectious complications following HiDAC consolidation. In patients with acute myeloid leukemia undergoing HiDAC consolidation, the role of prophylactic antimicrobials remains unclear. Prophylactic antimicrobials may not be necessary for all patients consolidated with HiDAC due to a potentially shorter course of neutropenia when compared to patients with AML undergoing induction chemotherapy, especially amongst younger AML patients. The use of antimicrobial prophylaxis should take into context patient and institutional factors. Disclosures Reagan: Pfizer: Research Funding; Takeda Oncology: Research Funding; Alexion: Honoraria.

Background: Classical Hodgkin lymphoma (cHL) displays near-universal genetic deregulation of PD-1 ligand expression, and relapsed/refractory (R/R) cHL is uniquely sensitive to PD-1 blockade. However, such treatment for patients (pts) who relapse after or are ineligible for autologous stem cell transplantation (ASCT) appears to be rarely, if ever, curative. Deploying PD-1 blockade early after ASCT could leverage the remodeling immune landscape and minimal residual disease state to increase the cure rate of ASCT. We therefore conducted a phase 2 multi-center single-arm study of the anti-PD-1 monoclonal antibody pembrolizumab (pembro) in pts with chemosensitive R/R cHL after ASCT. Another arm of this study enrolled pts with R/R DLBCL and will be presented separately. Methods: Adult pts with R/R cHL who had received 2-3 lines of prior therapy and ASCT and who were chemosensitive prior to ASCT were enrolled on this study. In addition to meeting standard eligibility criteria for pembro treatment, pts had to have recovered from ASCT toxicities and begin study treatment within 60 days of stem cell infusion (goal within 21 days). They received pembro 200mg IV every 3 weeks for 8 cycles. PET-CT scans were obtained at post-ASCT baseline, after 3 and 7 cycles, then at 12 and 18 months post-ASCT. The primary endpoint was the progression-free survival rate (PFS) at 18 months after ASCT, assessed using International Harmonization Project 2007 criteria. Results: 31 pts were enrolled and 1 withdrew consent before starting treatment. Among the 30 eligible patients, median age was 33 (20-69). 26 pts (87%) were high-risk by virtue of primary refractory disease (57%), relapse within 12 months (17%), extranodal disease at relapse (27%) or absence of metabolic CR at ASCT (10%). At study baseline post-ASCT, 97% were in CR. 24 pts (80%) completed 8 cycles of pembro per protocol. 6 pts (20%) stopped pembro early for pt choice (n=2, including 1 pt with gr2 pneumonitis) or toxicity (n=4, including 2 pts with gr3 hepatitis, 1 with g3 pneumonitis, 1 with g2 diplopia). 9 pts (30%) experienced a total of 28 gr3 or higher adverse events (AEs). The most common gr4 AE was neutropenia (10%). 3 patients (10%) experienced 7 gr3-4 AEs at least probably related to pembro (gr3 diarrhea and gr3 eosinophilic colitis in 1 pt, gr3 leukopenia and gr4 neutropenia in 1 pt, gr3 leukopenia and gr3 ALT and AST elevation in 1 pt). 11 pts (37%) experienced at least one immune-related AE of gr2 or higher severity: pneumonitis (n=2 gr2, n=1 gr3), thyroid dysfunction (n=1 gr2), transaminitis (n=2 gr3), colitis/diarrhea (n=1 gr2, n=2 gr3), rash (n=2 gr2), pulmonary hemorrhage (n=1 gr3), arthritis (n=1 gr2), and increased creatinine (n=1 gr2). There was no treatment-related death. Among the 30 eligible pts, 2 were lost to follow-up after their 12m assessments (both in CR). 27 pts (90%) were evaluable for the primary endpoint (the last pt is still in follow-up and results will be updated for the meeting). 6 patients (20%) relapsed at a median of 8 months (3-18) from ASCT, and all other evaluable patients were in CR at the 18m timepoint. The KM estimate of 18m PFS for high-risk patients was 78% (95%CI 54-91). The 18m overall survival was 100%. Tumor biopsies from a pt who progressed on study demonstrated an increase in the %age of PD1+ T cells at progression, as well as an increase in the %age of PD-L1+ macrophages and PD-L1+ Reed-Sternberg cells (Figure). Other correlative studies including immune reconstitution and MRD analyses are ongoing. Conclusions: Pembrolizumab administered after ASCT in patients with R/R cHL has a safety profile that appears similar to its use in the R/R setting, although possibly with a higher rate of neutropenia. The 18-month progression-free rate in this high-risk cohort compares favorably with previous published studies, and supports the hypothesis that PD-1 blockade in this setting may increase the efficacy of ASCT. This should be tested in a randomized trial. Figure. Figure. Disclosures Armand: Pfizer: Consultancy; Affimed: Consultancy, Research Funding; Otsuka: Research Funding; Merck: Consultancy, Research Funding; Infinity: Consultancy; Adaptive: Research Funding; Bristol-Myers Squibb: Consultancy, Research Funding; Roche: Research Funding; Tensha: Research Funding. Chen:Incyte: Consultancy, Membership on an entity's Board of Directors or advisory committees; Takeda Pharmaceuticals: Consultancy; Magenta Therapeutics: Consultancy; REGiMMUNE: Consultancy. LaCasce:Humanigen: Consultancy, Honoraria; Research to Practice: Speakers Bureau; Bristol-Myers Squibb: Other: Data safety and monitoring board; Seattle Genetics: Consultancy, Honoraria. Jacobson:Pfizer: Consultancy; Humanigen: Consultancy; Precision Bioscience: Consultancy; Novartis: Consultancy; Kite: Consultancy; Bayer: Consultancy. Jacobsen:Merck: Consultancy; Seattle Genetics: Consultancy. Rodig:Bristol-Meyers-Squibb: Research Funding; KITE Pharma: Research Funding; Affimed Inc.: Research Funding; Merck & Co., Inc.: Research Funding. Shipp:AstraZeneca: Honoraria; Bristol-Myers Squibb: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Bayer: Research Funding; Merck: Research Funding. Herrera:BMS: Consultancy, Research Funding; Merck: Consultancy, Research Funding; Genentech: Consultancy, Research Funding; Pharmacyclics: Consultancy, Research Funding; KiTE Pharma: Consultancy, Research Funding; Seattle Genetics: Research Funding; Immune Design: Research Funding; Astra Zeneca: Research Funding.

Objective: The long-term efficacy (June 2001 - May 2018) of newly diagnosed APL patients (pts) treated with either As4S4 or As2O3 in combination of all-trans retinoid acid (ATRA), and anthracycline-based chemotherapy in Lu Dao-Pei Hospital is analyzed. Methods: Firstly, 8 years from June 2001 to December 2009, a total of 88 newly diagnosed with APL patients were divided into two groups, who were treated with a protocol of either oral(po) As4S4 (n=42) or intravenous (IV) arsenic trioxide (ATO) (n=46) combined with ATRA and anthracycline-based chemotherapy. Secondly, 17 years from June 2001 till June 2018, 63 cases of newly diagnosed with APL patients were all treated with the protocol of oral As4S4 based triple-agents treatment. The oral As4S4 and IV ATO treatment protocols were as follows. In the first month of induction, either As4S4 60mg/kg/day po or ATO 0.15mg / kg IV × 30 days in combination with ATRA 45mg / m2/day po × 30 days and NVT1.5-3mg / kg IV × 5-7 days were given. This was followed by consolidation chemotherapy 3 to 5 cycles after CR, consistence with : ① IDA12mg/m2 IV×3d; ② Aar-C 75mg/m2 IV×7d + ACLA 14mg/m2×7d; ③ NVT 6mg/kg×3d; ④ Ara-C 75mg/m2×7d + HHT 1.4mg/m2×7d; ⑤MD-Ara-C (the fifth was only given to pts with WBC>10×109/L before treatment). After which, maintenance treatment was given either with As4S4 60mg/kg po or ATO 0.15mg / kg IV ×15d every 30 days. Both groups were also given ATRA 45mg/m2 po×15d every 30 days. The interval was increased by more than 15 days every half year. The total treatment duration lasted 3-4 years. Results:(1) All of the two groups who were treated with a protocol of either oral As4S4 (n=42) or IV arsenic trioxide (ATO) (n=46) from 2001 to 2009 reached 100% of molecular complete remission (MCR). The 8-year estimated disease-free survival (DFS) rate was 100% in oral As4S4 group with a median follow-up of 66 (15-109) months(mos). In ATO group, the DFS rate was 87.1% with a median follow-up of 42 (14-102) mos. The difference of the DFS rate between both groups was statistically significant (p=0.028, Log-Rank test). (2) In view of the outstanding DFS result in oral As4S4 group, after 2009, another 21 APL patients were treated with the protocol of oral As4S4. So in total 63 patients treated with the protocol of oral As4S4, there were 9 children and 54 adults, 24 cases with high WBC>10×109/L before treatment, 11 cases of additional chromosomal abnormalities other than t(15;17), 9 cases of central nervous system leukemia(CNSL), and 2 cases of FLT3-ITD positive in the 22 cases with FLT3 results. All the patients attained hematological complete remission (HCR) after induction therapy without treatment-related death and achieved MCR. The median duration of MCR time was 2 (1-7) mos. The long-term overall survival (OS) rate was 98.4%(Fig1) (one died from endometrial carcinoma), and DFS rate was 100%(Fig2) (With 2 cases relapsed, respectively because of hematological and CNS, of which the current DFS time were 40mos and 30mos after CR again). The median follow-up time was 124 (21-198) mos. Conclusions: APL patients treated with either oral As4S4 or IV As2O3 combined with ATRA and anthracycline-based chemotherapy can obtain 100% MCR and high long-term DFS. Compared with IV ATO, patients in oral As4S4 group achieved significantly better efficacy, with a 17-year DFS of 100%. Moreover, oral As4S4 is easy to give. Disclosures No relevant conflicts of interest to declare.

Patients with intermediate risk AML have unpredictable outcomes. Some do extremely well with conventional induction and consolidation chemotherapy, while others do poorly. The discovery of nearly all mutations associated with AML pathogenesis created an important database that has allowed investigators from around the world to use panel tests to assess the mutational landscapes of thousands of patients with known outcomes. Although these studies have been extremely informative, they have not dramatically altered the ability to accurately predict whether an individual intermediate-risk AML patient will relapse. The reasons are multifold. First, there is enormous combinatorial complexity of the mutations associated with AML. At least three mutations are required for the development of most AML cases, but since there are more than 250 recurrently mutated genes, the combinatorial possibilities are enormous. Secondly, because virtually all patients with AML present with clonal heterogeneity, and since individual subclones have different susceptibilities to chemotherapy, it has been difficult to predict outcomes based solely on the mutational composition of a patient at presentation. Further, since most subclones are 'invisible' to flow cytometric methods, and do not contain well-established mutations in genes that are recurrently mutated in AML, we cannot yet predict whether a subclone may be refractory to chemotherapy, or have extraordinary relapse potential . To overcome these issues, we asked whether information based on the clearance of the subclones from each patient could "integrate" this critical information in a practical way, and ultimately improve risk assessment. This study (Klco et al, JAMA 2015) suggested that a practical evaluation of mutation clearance after induction therapy could represent an improvement in our ability to predict whether intermediate risk patients who fail to clear their mutations after induction would benefit from allogeneic transplantation as their primary consolidation. A prospective clinical trial designed to answer this question is underway. Efforts to identify the properties of subclones that have high relapse potential, using single cell RNA-seq, and the sequencing of the relapse genomes of additional AML cases, will also be discussed. Disclosures No relevant conflicts of interest to declare.