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Severe (grade 3-4) acute GVHD (aGVHD) and NIH grade severe chronic GVHD (cGVHD) have historically been associated with poor survival. However, earlier diagnosis, improved treatment and supportive care, may result in an improvement in outcomes for patients recently diagnosed with severe GVHD compared to prior cohorts. Our institution has prospectively documented onset, grading and therapy of patients with GVHD using a single dedicated practitioner since 2005. We assessed 851 consecutive patients who received allografts at our center between 1/2005 and 12/ 2016 and identified 130 patients (15.3%) who developed severe aGVHD through Dec 2017 without prior relapse of malignancy. Characteristics were: median age 52.5, 51% male, race-81% white -17% black, diagnosis- AML 31% - MDS/MPD 20%- NHL/HL/CLL-23%, -ALL 11%, donor - MRD 21% - MUD 49% - haplo 30%, PBSC 78%, BM 17%, CBU 5%, preparative regimen MAC 44% - RIC/NST 56%, median time from BMT to onset of severe aGVHD was 49 days (7-376). Maximum grade = gd 3 (85%), gd 4 (15%), Median follow-up for survivors from date of onset was 59 months (23-155m). Survival estimates for the entire cohort from date of onset of grade 3-4 aGVHD at 1, 2 and 3 years were 62%, 49% and 47% respectively. Patients who developed severe aGVHD in 2016-2017 had significantly improved overall survival compared to patients who developed severe acute GVHD in prior years (2005-2015) -1 and 2 yr survival 86% & 79% vs 55% & 41% respectively, p=0.002 log-rank test, Fig 1). No significant differences were found between earlier cohorts. On multivariable analysis assessing the following variables: age, gender, race, diagnosis, donor type, cell source, regimen intensity, DRI, HCT-CI, CMV status, grade of aGVHD (3 vs 4), days from transplant to gd 3-4 aGVHD onset, year of development of severe acute GVHD (2016-2017 vs earlier) remained significant for survival (HR 0.36, p=0.018). Other significant variables were grade 4 vs 3 GVHD (HR 3.78, p For cGVHD we assessed 522 consecutive patients who underwent allografts between 4/2011 (start date of prospective documentation of NIH grade cGVHD )and 12/2016, and identified 146 (28%) patients who developed moderate to severe NIH grade chronic GVHD without prior relapse by Dec 2017 (85 severe, 61 moderate). Patient characteristics were: median age 53, 55% male, race-74% white -22% black, AML 40% - MDS/MPD 31%- NHL/HL/CLL-15%, -ALL 12% , donor - MRD 34% - MUD 40% - haplo 25%, graft- PBSC 82%, BM 18%, preparative regimen MAC 54% - RIC/NST 44%, median time from BMT to onset of moderate/severe cGVHD was 289 days (27-1364). Median follow-up for survivors from date of onset of moderate to severe GVHD was 48 months (19-94m). Estimated rates of survival from date of onset of moderate to severe cGVHD for the entire cohort at 1, 2 and 3 years were 82%, 73% and 71% respectively. For patients who developed severe cGVHD the corresponding survival estimates were 77%, 67% and 63%. No significant difference in post-onset survival was encountered when comparing patients developing moderate cGVHD in 2011-2013, 2014-2015 and 2016-2017. However, for severe cGVHD, 1 and 2 year estimated survival rates for the three cohorts were : 53% & 41%, 79% & 73% and 87% and 74% respectively (p=0.004 for 2011-2013 vs 2014-2015 but p=NS for 2014-2015 vs 2016-2017, Fig 2). On a multivariable analysis considering age, gender, race, diagnosis, donor type, graft source, regimen intensity, DRI, HCT-CI, and days from transplant to cGVHD onset, none of these variables was significantly associated with post-cGVHD survival. In the Cox model including year of onset of severe cGVHD, onset in recent years was linked to lower risk of mortality compared to onset in earlier years (onset 2014-2015 vs 2011-2013 - HR=0.34, p-0.012; onset 2016-2017 vs 2011-2013 - HR=0.28, p=0.006). These data suggest that survival of patients developing either severe aGVHD or severe NIH grade cGVHD has significantly improved in recent years compared to historical controls. More than two-thirds of such patients now survive two years from onset of severe GVHD. This must be taken into account when evaluating novel therapies for severe GVHD. Disclosures Solh: ADC Therapeutics: Research Funding; Celgene: Speakers Bureau; Amgen: Speakers Bureau.

Phase II trial evaluating the Efficacy and Safety of Sargramostim Post Infusion of T -Replete HLA Mismatched Peripheral Blood Haploidentical Hematopoietic Stem Cells with Post-Transplant Cyclophosphamide Background: T-replete HLA mismatched haploidentical transplantation (Haplo) with post-transplant cyclophosphamide (PTCY) is widely used for patients lacking a suitably matched donor. Patients who receive haplo with PTCY usually start growth factor support (G-CSF) on day +5 for neutropenia prophylaxis. G-CSF is a specific stimulator of the growth and differentiation of hematopoietic progenitor cells committed to the neutrophil lineage. Granulocyte-macrophage colony-stimulating factor (GM-CSF) on the other hand, is not restricted to neutrophils because it also affects monocytes and eosinophils and plays a central role in antifungal host response. In a prior randomized study among 206 matched allogeneic HCT patients (wang et al, J Clin Oncol. 2015;33(34):3999-4006), neutropenia prophylaxis with GM-CSF +/- G-CSF had significantly lower 100-day TRM, lower 100-day cumulative mortality, lower infection related mortality and lower 600-day invasive fungal disease related mortality compared to G-CSF. Given the increase number of HLA mismatched haplos with PTCY performed each year and the high risk of infectious complications associated with this type of transplant, we suggest that GM-CSF administration post haplo and PTCY can yield similar count recovery rate to GCSF with a potential of lowering risk of infectious complications. Endpoints : The primary endpoint is to establish equivalent effectiveness of sargramostim to a matched control cohort of G-CSF treated patients in time to neutrophil engraftment (ANC>500 x 3 days) post haplo with PTCY. Secondary endpoints: estimates of OS, DFS, relapse rate, GVHD and TRM. Donor chimerism at days 30, 60, 100 and 6 months post-transplant. Incidence and grade of cytokine release syndrome between day 0 and 30. Incidence of infectious complications and infection related mortality at day 100. Immune profiling assay "CYTOF" will be measured at days 30, 60, 90 and 180 for functional and phenotypic immune analysis. Other secondary endpoints include length of hospital stay and charges-based cost comparison during the first 100 days between sargramostim and G-CSF matched controls. All primary and secondary endpoints will be reported for the study group and compared to a matched control cohort from our database containing patients who received haplo with PTCY using G-CSF for neutropenia prophylaxis. A set of 20 patients, who are not on the Sargramostim study and receiving haplo transplant with G-CSF at the same time of the study accrual period, will be consented for immunoprofiling assay at days 30, 60, 100 and 180. Methods: Patients aged 18-78 years with an available 5/10-8/10 HLA- matched related donor with high risk hematological malignancy with adequate organ function will be enrolled for the study. Patients will receive Sargramostim 250mg/m2 /day subcutaneous starting day +5 post haplo/PTCY and continue till ANC>1000x 3 days or >1500x 1 day. If grade 3 or 4 adverse reactions occur, reduce dose by 50% or temporarily discontinue the dose until the reaction abates. Conditioning regimens to be used include previously published and currently used at our center (Flu/Cy/TBI, Flu/high dose TBI or Flu/Mel). Treatment will be in the outpatient setting and admissions if clinically indicated. Sample Size Determination : Time to ANC>500 will be evaluated between the prospectively enrolled patients and matched historical controls. Based on the data of haplo transplants done at Northside in 2010-2016, the standard deviations (SD) was 3 days for time to ANC500. The correlation in measurements between prospective patient and matched control is conservatively assumed to be 0.1. SD for differences between matched pairs would be 3.55 days for time to ANC500. To control the type I error to be 5%, the 90% paired t confidence interval for difference in time to ANC500 should be constructed and its upper boundary will be compared to the non-inferiority margin 2 days. The size of 35 prospective patients provides the power 90% for concluding that time to ANC500 for Sargramostim is no more than 2 days longer than historical controls. The actual enrollment size is decided to be 38 to accommodate 10% of drop off rate. Enrollment: The study is expect to start enrolling patients October 2019. Disclosures No relevant conflicts of interest to declare.

Background: Allogeneic hematopoietic cell transplantation (HCT) has been a successful strategy to treat myelodysplastic syndrome (MDS). With only approximately one-third of patients having an HLA matched sibling, most transplants use mismatched relative (haploidentical) or unrelated donors. In the current analysis we sought to study outcomes after haploidentical related compared to HLA-matched unrelated donor HCT for MDS (de novo or therapy-related). Methods: We retrospectively studied 176 recipients of haploidentical related donor and 427 recipients of 8/8 HLA-matched unrelated donor HCT in the United States between 2012 and 2017. The primary outcome was overall survival. The effect of donor type on survival and other transplant outcomes were studied using a Cox regression model. Results: Patient and disease characteristics are presented in Table 1. Most transplants (85%) were for de novo MDS in both donor groups. Although all patients received reduced intensity regimens, the predominant conditioning regimens were confounded by donor type. Total body irradiation (TBI) 200 cGy/cyclophosphamide/fludarabine (TBI/Cy/Flu; 82%) was the predominant regimen for haploidentical HCT and fludarabine with busulfan or melphalan (Flu/Bu or Flu/Mel; 79%) without in vivo T-cell depletion was the predominant regimen for unrelated donor HCT. Similarly, graft-versus-host disease (GVHD) prophylaxis was also confounded by donor type. Posttransplant cyclophosphamide/calcineurin inhibitor/mycophenolate (PT-Cy/CNI/MMF) was the prophylaxis regimen for all haploidentical transplants. CNI/MMF (31%) or CNI/methotrexate (69%) was used for unrelated donor transplants. Peripheral blood was the predominant graft for both donor types. The median follow-up was 24 months (range 3-77) after haploidentical and 36 months (range 3-74) after unrelated donor HCT. Results of multivariate analysis, adjusted for HCT-CI, prior treatment with hypomethylating agents (HMAs), and IPPS-R did not show differences in survival by donor type (HR 0.98, p=0.85; 40% vs. 37%), Figure 1. However, the relapse rate (adjusted for prior HMAs, IPSS-R, and recipient sex) was higher after haploidentical compared to unrelated donor HCT (HR 1.60, p=0.002, 53% vs. 34%), which led to lower disease-free survival after haploidentical HCT (HR 1.30, p=0.03; 21% vs. 32%), Figure 1. To further test the effect of regimen intensity, low dose TBI regimens were compared to Flu/Bu and Flu/Mel; we did not observe a difference in relapse risk (HR 0.95, p=0.76). Non-relapse mortality did not differ by donor type (HR 0.88, p=0.46). Interval between diagnosis and transplant was also not associated with outcomes. Acute grade II-IV acute GVHD (HR 0.46, p Conclusion: Although the current analysis did not show differences in survival between haploidentical related and matched unrelated donor HCT, the higher relapse and consequently lower disease-free survival associated with the haploidentical HCT approach in this analysis (primarily TBI/Cy/Flu with PT-Cy/CNI/MMF) warrants caution. A more definitive comparison of the two donor types can be accomplished only if more haploidentical transplants were to use Flu/Bu or Flu/Mel conditioning. Figure 1 Disclosures Grunwald: Celgene: Consultancy; Pfizer: Consultancy; Agios: Consultancy; Merck: Consultancy; Abbvie: Consultancy; Medtronic: Equity Ownership; Incyte: Consultancy, Research Funding; Daiichi Sankyo: Consultancy; Amgen: Consultancy; Trovagene: Consultancy; Cardinal Health: Consultancy; Janssen: Research Funding; Genentech/Roche: Research Funding; Novartis: Research Funding; Forma Therapeutics: Research Funding. Bolanos-Meade:Incyte Corporation: Other: DSMB fees. Bredeson:Otsuka: Research Funding. Gupta:Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; 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; Incyte: Honoraria, Research Funding. Mussetti:Takeda: Honoraria; BMS: Honoraria; Novartis: Honoraria; Italfarmaco: Honoraria. Nakamura:Merck: Membership on an entity's Board of Directors or advisory committees; Celgene: Other: support for an academic seminar in a university in Japan; Alexion: Other: support to a lecture at a Japan Society of Transfusion/Cellular Therapy meeting ; Kirin Kyowa: Other: support for an academic seminar in a university in Japan. Nishihori:Novartis: Research Funding; Karyopharm: Research Funding. Solh:Celgene: Speakers Bureau; Amgen: Speakers Bureau; ADC Therapeutics: Research Funding. Weisdorf:Fate Therapeutics: Consultancy; Pharmacyclics: Consultancy; Incyte: Research Funding.

Relapse of leukemia (RL) is the most common cause of treatment failure following allogeneic hematopoietic cell transplantation (alloHCT) in patients with AML. Historically, patients who suffer RL following alloHCT have had a dismal prognosis. A number of therapeutic options have recently become available for relapsed/refractory AML, including some that are associated with limited toxicity and may be well tolerated in the post-alloHCT setting. These therapies, and advances in supportive care have the potential to prolong survival of recently transplanted patients who suffer RL post post-alloHCT compared to prior cohorts. We hypothesized that patients suffering RL post-alloHCT within the last 5 years will have improved post-relapse survival compared to patients experiencing RL before this period. In order to test this hypothesis, we analyzed 309 patients who underwent a first allo-HCT for AML between Jan 2002 and Dec 2016 at our center and identified 112 patients (36%) who suffered RL post-alloHCT. Data were extracted from our institutional BMT database where they had been prospectively entered. Patient characteristics of those who experienced RL were: median age 53 (19-74); male - 51%; race- white-86%, black 12%, Asian -2%; donor-MRD 33%, MUD 41%, Haplo 26%; graft source - PBSC 86%, BM 11%, CBU 2%, PBSC+BM 1%; regimen intensity - MAC 61%, NST/RIC 39%%; DRI - intermediate 46%, high 50%, v. high 5%; HCT-CI 0-2 (58%), >3 (42%); KPS > 90 (39%) 250 d vs Disclosures Solh: ADC Therapeutics: Research Funding; Celgene: Speakers Bureau; Amgen: Speakers Bureau.

Unmanipulated T-cell replete HLA-mismatched haploidentical transplantation (haplo) with post-transplant cyclophosphamide (PTCY) is now widely used for patients lacking a suitably matched donor. The use of PTCY post haplo results in lower chronic GVHD rates compared to match unrelated donors (MUD) without PTCY. GVHD after PTCY in the haplo setting may have different presentation, response to treatment and impact on survival endpoints compared to a standard GVHD prophylaxis of calcineurin inhibitor plus MMF or methotrexate for MUD patients. To check for differences in GVHD presentation and response to treatment between MUD and haplo with PTCY, we assessed 394 consecutive patients who developed acute or chronic GVHD after receiving their first allogeneic transplantation (HCT) from a 10/10 HLA MUD (n=179) or a haplo (n=215) at our center between 2008 and 2017. Median follow up for survivors was 52.5 months. Our institution has prospectively documented onset, grading and therapy of patients with GVHD using a single dedicated practitioner since 2005. All haplo patients received standard GVHD prophylaxis of tacrolimus (days 5-180), MMF (stop day 35) and PTCY at 50mg/kg on days 3 and 4. Most commonly used GVHD prophylaxis for MUD patients were tacrolimus/methotrexate (68%) and tacrolimus/MMF (26%). MUD recipients were older (median age 56 vs 53 years, p=0.007), were more likely to be white (93% vs 58%, p=55), gender, race, diagnosis, regimen intensity, graft source (BM, PBSC), disease risk index (low/intermediate, high/very high), CIBMTR risk (low, intermediate, high), HCT-CI (0-2, >=3), CMV status, year of transplantation (2008-2012, 2013-2015, 2016-2017). The following variables were evaluated as time-dependent covariates in Cox models: all-grade cGVHD, moderate-severe cGVHD, severe cGVHD, grade 2-4 aGVHD, grade 3-4 aGVHD. Variables were selected if p values were less than 0.05. Developing grade 3-4aGVHD and severe chronic GVHD were both associated with worse OS, DFS and TRM (table 2). Both aGVHD and cGVHD were not significant factors for relapse. Our analysis reveals that compared to MUD, haplo transplant results in significantly lower incidence of moderate-severe chronic GVHD, faster cGVHD onset, different organ distribution and a higher chance of coming off immunosuppression. This data, added to prior publications from our center and others showing similar OS and DFS between MUD and haplo, enforces the notion that haplo transplant with PTCY is at least equivalent to MUD transplant. An ongoing BMTCTN 1702(CTRL-ALT-D) study will help answer assess this in a prospective fashion. figure 1: Chronic GVHD patients who are Immunosuppression free at 2 years Table 1: Organ Distribution of Chronic GVHD by Donor Type Disclosures No relevant conflicts of interest to declare.

Introduction: Patients (pts) with relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL) after hematopoietic cell transplant or chimeric antigen receptor T-cell therapy, or those who are ineligible for such therapies, need more treatment options. Loncastuximab tesirine (ADCT-402; Lonca) is an antibody-drug conjugate (ADC) comprising a humanized antibody directed against human CD19 conjugated to a pyrrolobenzodiazepine dimer toxin. Its target, the human CD19 antigen, is a classic B-cell marker expressed at normal-to-high levels on the majority of malignant B-cells. Preliminary data from a Phase 1 dose-escalation and dose-expansion trial of Lonca in R/R B-cell non-Hodgkin lymphoma showed significant clinical activity in DLBCL, with an acceptable safety profile, and the recommended Phase 2 dose of 150 μg/kg was identified. Here, we present the planned interim analysis for futility on the first 52 pts with R/R DLBCL treated with Lonca in Phase 2. Methods: This single-arm, multi-center, open-label, two-stage, Phase 2 trial is currently enrolling pts ≥18 years of age with R/R DLBCL following ≥2 multi-agent systemic treatment regimens and without bulky disease (tumor ≥10 cm). The primary objective is to evaluate the efficacy of single-agent Lonca by overall response rate (ORR). The secondary objectives are to further evaluate efficacy (including duration of response [DOR], progression-free survival [PFS], and overall survival [OS]), to characterize the safety, pharmacokinetics and immunogenicity profile of Lonca, and to evaluate the impact of Lonca on health-related quality-of-life. Pts received 30-minute intravenous infusions of Lonca once every 3 weeks (1 cycle) at a dose of 150 μg/kg for the first 2 cycles, then 75 μg/kg for subsequent cycles, for up to 1 year or until disease progression, unacceptable toxicity, or other discontinuation criteria, whichever occurs first. A preplanned interim analysis for futility was conducted when the 52nd pt would have had 2 tumor assessments (approximately 12 weeks after the start of study drug), with the study planned to proceed to full enrollment if ≥10 of the first 52 pts responded to Lonca. ORR (complete response [CR] + partial response [PR]) was determined by an independent reviewer. Results: 52 pts with DLBCL were included in the interim analysis. Pts had a median age of 62.5 years [range 24-84] and had received a median of 3 previous therapies (range 2-7; Table 1). As of the data cut-off of May 01, 2019, pts had received a median of 2.5 (range 1-9) cycles of Lonca. ORR among the futility analysis population (52) was 44.2%, meeting futility requirements. A total of 10/52 (19.2%) and 13/52 (25.0%) pts attained CR and PR, respectively. In addition, 11 pts (21.2%) had stable disease (Figure 1). All (100%) pts had at least 1 treatment-emergent adverse event (TEAE), and 37 (71.2%) pts had grade ≥3 TEAEs. The most common all-grade non-hematological TEAEs, regardless of relationship to study treatment, were gamma-glutamyltransferase (GGT) increase (24 [46.2%]), pyrexia (18 [34.6%]) and hypokalemia (15 [28.8%]); pleural effusions and peripheral edema were reported in 5/52 pts (9.6%) and 6/52 pts (11.5%), respectively; 1 of these pts had a grade ≥3 event (pleural effusion). The most common grade ≥3 TEAEs were GGT increase (11 [21.2%]), hypercalcemia (4 [7.7%]) and hypokalemia (3 [5.8%]). No grade ≥3 skin-related TEAEs have been reported. The most common all-grade hematological abnormalities were platelet count decreased* (34 [65.4%]), neutrophil count decreased* (27 [51.9%]) and anemia (14 [26.9%]), and the most common grade ≥3 hematological abnormalities were neutrophil count decreased* (15 [28.8%]), platelet count decreased* (10 [19.2%]) and anemia (6 [11.5%]). Overall, 26 (50%) pts had TEAEs leading to dose reductions/delays and 10 (19.2%) pts had TEAEs leading to treatment discontinuation. Conclusions: Lonca has demonstrated encouraging single-agent anti-tumor activity and manageable toxicity in pts with R/R DLBCL. Futility requirements were met and pts are now enrolling in stage 2 of the trial. Updated efficacy results will be presented at the meeting. *Laboratory abnormality data are reported for platelet count decreased and neutrophil count decreased to avoid under-reporting of these events. Study sponsored by ADC Therapeutics SA. http://clinicaltrials.gov/show/NCT03589469 Disclosures Carlo-Stella: Amgen: Honoraria; Boehringer Ingelheim: Consultancy; AstraZeneca: Honoraria; Novartis: Consultancy, Research Funding; ADC Therapeutics: Consultancy, Other: Travel, accommodations, Research Funding; Sanofi: Consultancy, Research Funding; Rhizen Pharmaceuticals: Research Funding; Takeda: Other: Travel, accommodations; Celgene: Research Funding; F. Hoffmann-La Roche Ltd: Honoraria, Other: Travel, accommodations, Research Funding; Genenta Science srl: Consultancy; Servier: Consultancy, Honoraria, Other: Travel, accommodations; Janssen: Other: Travel, accommodations; Janssen Oncology: Honoraria; BMS: Honoraria; MSD: Honoraria. Zinzani:VERASTEM: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; ROCHE: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; PORTOLA: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; MSD: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; CELLTRION: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; GILEAD: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; JANSSEN-CILAG: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; BMS: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; KYOWA KIRIN: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; SANOFI: Consultancy; IMMUNE DESIGN: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; EUSAPHARMA: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; CELGENE: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; SERVIER: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; SANDOZ: Membership on an entity's Board of Directors or advisory committees. Kahl:BeiGene: Consultancy; TG Therapeutics: Consultancy; ADC Therapeutics: Consultancy, Research Funding; Seattle Genetics: Consultancy. Caimi:ADC Therapeutics: Research Funding; Genentech: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Fate Therapeutics: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Kite Pharmaceuticals: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Celgene: Speakers Bureau. Solh:ADC Therapeutics: Research Funding; Amgen: Speakers Bureau; Celgene: Speakers Bureau. Townsend:Roche: Consultancy, Honoraria. Stathis:PharmaMar: Other: Renumeration; Roche: Other: Institutional research funding; Pfizer: Other: Institutional research funding; MEI-Pharma: Other: Institutional research funding; Novartis: Other: Institutional research funding; Merck: Other: Institutional research funding; Bayer: Other: Institutional research funding; Abbvie: Other: Renumeration; ADC Therapeutics: Other: Institutional research funding. Cull:ADC Therapeutics: Research Funding; Celgene: Speakers Bureau. Hamadani:Otsuka: Research Funding; ADC Therapeutics: Consultancy, Research Funding; Sanofi Genzyme: Research Funding, Speakers Bureau; Celgene: Consultancy; Takeda: Research Funding; Medimmune: Consultancy, Research Funding; Janssen: Consultancy; Pharmacyclics: Consultancy; Merck: Research Funding. Spira:Novartis: Research Funding; Roche: Research Funding; Boehringer Ingelheim: Research Funding; ADC Therapeutics: Research Funding; Abbvie: Research Funding; Astellas Pharma: Research Funding; Incyte: Research Funding; AstraZeneca: Research Funding; Newlink Genetics: Research Funding; BMS: Consultancy; Virginia Cancer Specialists: Employment; MedImmune: Research Funding. Feingold:ADC Therapeutics: Employment, Other: Potential equity interest. Ungar:ADC Therapeutics: Employment, Other: Stock options. equity interest. He:ADC Therapeutics: Employment, Other: Potential equity interest. Qin:ADC Therapeutics: Consultancy, Other: Potential equity interest. Radford:AstraZeneca: Equity Ownership, Research Funding; BMS: Consultancy, Honoraria; Takeda: Consultancy, Honoraria, Research Funding; Novartis: Consultancy, Honoraria; ADC Therapeutics: Consultancy, Research Funding; GSK: Equity Ownership; Seattle Genetics: Consultancy, Honoraria.

Inhibition of the ubiquitin-proteasome proteolytic pathway results in extensive immunomodulatory effects, augmenting NK cell cytotoxicity while inhibiting aspects of T-, B- and dendritic cell function. To this end, short course bortezomib has been utilized post-transplant to decrease the risk of graft-versus-host disease (GVHD) while preserving graft-versus-malignancy (GVM) effects (Koreth, Haematologica 2018). We performed a phase II study examining the effects of ixazomib for GVHD prophylaxis (up to 12 cycles), in addition to post-transplant cyclophosphamide and tacrolimus, following the original Baltimore nonmyeloablative haploidentical transplant (HIDT) regimen. We hypothesized that substituting ixazomib for mycophenolate would provide acceptable GVHD control while potentially augmenting GVM. Ixazomib was started on day +5 at a dose of 4mg on days 1, 8, 15 of a 28-day cycle, with dose reductions allowed in future cycles for toxicity and mycophenolate, used for conventional post-HIDT GVHD prophylaxis, was eliminated. Donors were selected to maximize NK alloreactivity (i.e. B/x KIR haplotype). Twenty-five patients were enrolled, median age 62 (range 35-77) years, with acute leukemia [4], MDS [7], NHL/HL/CLL [8] and myeloma [6]. Comorbidity index (HCT-CI) was ≥3 in 68%. Donor KIR haplotype was B/x and A/A in 18 and 7 patients respectively. After a median follow-up of 33.5 months (range 9.2-52.8), 19 patients survive with an estimated 1- and 3-year overall survival of 84% and 74% respectively. Engraftment occurred in all patients with no secondary graft failure. Median time to ANC>500 and PLT>20 was 16 and 29 days respectively. CMV reactivation was frequent occurring in 88% of CMV-seropositive patients, however there was no cases of CMV disease. Infectious mortality occurred in 3 patients (disseminated adenovirus, HHV6 encephalitis and fungal pneumonia). The 3-yr cumulative incidence of non-relapse mortality (NRM) was 12% but was significantly higher when the donor possessed the more inhibitory KIR A/A vs. stimulatory B/x haplotype (43% vs. 0%). Relapse incidence at 1- and 3-years was 24% and 44%. Cumulative incidence of Grade 3-4 acute GVHD at day +180 was 8%, while 2-year moderate-to-severe chronic GVHD occurred in 21%. Hematologic and cutaneous toxicities possibly related to ixazomib were common, resulting in dose reductions and treatment interruptions in most patients. Median number of ixazomib cycles was 3 (range 1-12), with only one patient receiving all 12 planned cycles. Rash, at least possibly related to ixazomib, was particularly frequent occurring in 19 (76%) patients at a median day +32 (range, 17-139) following transplant. Reasons for early ixazomib discontinuation included rash [9], cytopenias [7], relapse/progression [4], GVHD [2], diarrhea [1] and arthralgias [1]. In conclusion, the substitution of ixazomib for mycophenolate post-HIDT is feasible and results in reliable engraftment with low rates of clinically significant GVHD and NRM, without any appreciable effect on relapse protection. The occurrence of rash in the first several months in three quarters of patients was unexpected and made it difficult to distinguish drug toxicity from low-grade skin-only acute GVHD. The finding that Infectious mortality occurred exclusively in recipients of KIR A/A haplotype donors is interesting and requires further study. Figure Disclosures Solh: Celgene: Speakers Bureau; Amgen: Speakers Bureau; ADC Therapeutics: Research Funding. OffLabel Disclosure: Use of ixazomib for GVHD prophlaxis following haploidentical transplantation.

Background: PLX2853 is an orally available, non-benzodiazepine BET (bromodomain and extraterminal domain) inhibitor that exhibits low nanomolar potency and a modest preference for binding to the second bromodomain (BD2) of the BET proteins. By regulating genes (e.g. MYC and BCL2) critical to leukemic cell growth and survival, PLX2853 demonstrated broad anti-leukemic activity both as a single agent and in combination with other therapeutic agents in preclinical models. The pharmacokinetic (PK) profile in solid tumor patients revealed a short half-life (< 3 hour) enabling high peak plasma concentrations and nearly complete elimination from the plasma 9 hour post dose. Since strong and prolonged suppression of BET proteins have often untoward effects in normal tissues, the PLX2853 PK profile is hypothesized to be associated with improved tolerability by allowing transient target engagement followed by time for recovery after daily dosing. Methods: We are conducting an open-label, Phase 1b (Ph1b) study of PLX2853 as a single oral agent administered daily in adult patients with relapsed or refractory acute myeloid leukemia (AML) or high risk myelodysplastic syndrome (MDS) using a modified continuous reassessment model (mCRM) with escalation with overdose control (EWOC) to determine the recommended phase 2 dose (RP2D). Up to 36 patients are expected to enroll. The dosing cycle and dose limiting toxicity window (DLT) is 21 days. Primary objectives include safety and PK. Secondary objectives include measures of preliminary efficacy, and exploratory objectives include pharmacodynamics (PD) biomarker assessments in various tissues. Enrollment through Cohort 2 (40 mg QD) is ongoing as of July 2019. Results: Five subjects with relapsed or refractory AML (median age 65 years) have received PLX2853 in escalating doses from 20 to 40 mg QD. Among these first 5 patients treated, the most common treatment emergent adverse events (AEs) regardless of causality in > 1 patient: decreased appetite (n=3), nausea (n=2), diarrhea (n=2), peripheral edema (n=2), cough (n=2), oropharyngeal pain (n=2), blood bilirubin increase (n=2), anemia (n=2), febrile neutropenia (n=2), fatigue (n=2), bacteremia (n=2), headache (n=2), dyspnea (n=2), and hypertension (n=2). Most were grade (G) 1-2. Treatment emergent AEs > G2 in > 1 patient included: anemia (n=2), febrile neutropenia (n=2) and hypertension (n=2). No treatment-related serious AEs or DLTs have been observed. Following a 20 mg daily dose of PLX2853, median time to reach maximal plasma concentrations (Tmax) is 1 hour and the absorption half-life (T1/2) is < 3 hours. Conclusions: In an ongoing Ph1b study, PLX2853 has now completed its first dosing cohort for patients with relapsed or refractory AML or high risk MDS, and no DLT has been observed yet. As dose escalation continues, PK, PD, preliminary safety and efficacy data will be assessed further to determine the clinical significance of target engagement. This clinical trial is registered at clinicaltrials.gov: NCT03787498. Disclosures Pemmaraju: mustangbio: Consultancy, Research Funding; abbvie: Consultancy, Honoraria, Research Funding; samus: Research Funding; celgene: Consultancy, Honoraria; cellectis: Research Funding; Stemline Therapeutics: Consultancy, Honoraria, Research Funding; novartis: Consultancy, Research Funding; plexxikon: Research Funding; Daiichi-Sankyo: Research Funding; sagerstrong: Research Funding; affymetrix: Research Funding; incyte: Consultancy, Research Funding. Borate:Novartis: Consultancy; Takeda: Consultancy; Pfizer: Consultancy; Daiichi Sankyo: Consultancy; AbbVie: Consultancy. Solh:ADC Therapeutics: Research Funding; Amgen: Speakers Bureau; Celgene: Speakers Bureau. Borthakur:Polaris: Research Funding; Arvinas: Research Funding; Agensys: Research Funding; Tetralogic Pharmaceuticals: Research Funding; Cantargia AB: Research Funding; Argenx: Membership on an entity's Board of Directors or advisory committees; BioLine Rx: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Oncoceutics, Inc.: Research Funding; Eli Lilly and Co.: Research Funding; BMS: Research Funding; AstraZeneca: Research Funding; Bayer Healthcare AG: Research Funding; Novartis: Research Funding; FTC Therapeutics: Membership on an entity's Board of Directors or advisory committees; AbbVie: Research Funding; Strategia Therapeutics: Research Funding; Cyclacel: Research Funding; Xbiotech USA: Research Funding; Eisai: Research Funding; Merck: Research Funding; BioTheryX: Membership on an entity's Board of Directors or advisory committees; Oncoceutics: Research Funding; NKarta: Consultancy; Incyte: Research Funding; Janssen: Research Funding; GSK: Research Funding; PTC Therapeutics: Consultancy. DeZern:Astex Pharmaceuticals, Inc.: Consultancy; Celgene: Consultancy. Zhang:Plexxikon Inc.: Employment. Powell:Plexxikon Inc.: Employment. Severson:Plexxikon Inc.: Employment. Inokuchi:Plexxikon Inc.: Employment. Matusow:Plexxikon Inc.: Employment. Halladay:Plexxikon Inc.: Employment. Hsu:Daiichi Sankyo, Inc.: Employment. Watkins:Plexxikon Inc.: Employment. Walling:Myovant Sciences: Consultancy; Nurix: Consultancy; Aduro Biotech: Consultancy; Plexxikon: Consultancy; CytomyX: Consultancy; Flag Therapeutics: Consultancy; Aminex: Consultancy; Immunext: Consultancy; SensenBio: Consultancy; Harpoon Therapeutics: Consultancy. Tsiatis:Plexxikon Inc.: Employment. Mims:PTC Therapeutics: Membership on an entity's Board of Directors or advisory committees; Astellas Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees; Jazz Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees; Abbvie: Membership on an entity's Board of Directors or advisory committees; Agios Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees.

HLA-haploidentical (haplo) stem cell transplantation is now widely used for patients lacking a suitably matched related or unrelated donor (MUD). Conventionally, T-replete Haplo transplantation has been performed using non-myeloablative conditioning and a bone marrow graft. Subsequently, our group has developed the use of myeloablative conditioning and PBSC grafts for Haplo (Solomon et al BBMT 2015, 2019). However, some patients with hematologic malignancies who are unable to tolerate a fully myeloablative regimen may benefit from intermediate intensity conditioning. We conducted a prospective phase II trial utilizing melphalan based preparative regimen ( fludarabine 30mg/m2 days -6 to -2, melphalan 140 mg/m2 day -1) followed by infusion of unmanipulated peripheral blood stem cells (PBSCs) ,capped at 5x10 6 CD34+/kg,from a haploidentical first degree family donor. Graft-versus-host disease (GVHD) prophylaxis consisted of Cy 50mg/kg on days 3 and 4, MMF through day 35, and tacrolimus through day 180. The primary endpoint was to estimate the incidence of graft rejection following Fludarabine/Melphalan conditioning. For the graft failure endpoint we tested the hypotheses H0: p=10% versus Ha: p Haplo transplant using fludarabine/melphalan with PBSCs is a valid option for some patients lacking a timely access to a matched donor. It is well tolerated and provides full and rapid donor myeloid and T-cell chimerism. Figure 1:Overall Survival and Disease Free Survival In Matched Cohorts of Flu/Mel versus Flu/Cy/TBI Figure 1 Disclosures No relevant conflicts of interest to declare.

Psychological and social factors are utilized as important part of the evaluation process for patients undergoing allogeneic hematopoietic stem cell transplantation (HSCT). The integration of such factors into the selection of suitable candidates and predicting survival post HSCT is still not widely incorporated in HSCT as it is the case in solid organ transplantation. To evaluate the impact of psycho social risks on post HSCT outcomes such as overall survival (OS), transplant related mortality (TRM), disease free survival (DFS), relapse and length of hospital stay, we prospectively conducted psycho social assessment on 556 consecutive allogeneic HSCT recipients who received their first transplant at our center between 2005 and 2017. The Transplant evaluation rating scale (TERS) has been previously published and was found to be psychometrically sound within the HSCT population(Hoodin, F. and Kalbfleisch, KR., Journal of Psychosomatic Research, 2003.) . TERS score was prospectively assessed by a psychologist prior to transplantation and patients were labeled as low/intermediate risk versus high risk based on their TERS score. All patients were transplanted in the outpatient setting with admission to the inpatient unit if clinically warranted. Five hundred and seven low/intermediate TERS patients and 49 high TERS were included in the analysis. Patients in the low/intermediate risk TERS group were more likely to have a higher disease risk index (17% versus 10%, p80) and year of transplant ( 2005-2009, 2010-2014, 2015-2017). High TERS score predicted for worse OS (HR 2.04; 95% CI 1.32-3.17; p=0.002), worse DFS (HR 1.71, 95% CI 1.12-2.63, p0.014), a trend towards higher TRM (HR 1.62, 95% CI 0.86-3.05, p0.136) and relapse (HR 1.56, 95% CI 0.87-2.78, p=0.132) (table 1). In a subset analysis of patients with low/intermediate disease risk, multivariate analysis showed that high TERS predicted for worse OS (HR 1.97, 95% CI1.24-3.14, p=0.004), DFS (HR 1.74, 95% CI 1.10-2.75, p=0.018), trend for higher TRM (HR 1.91, 95% CI 0.98-3.72, p=0.057) and similar relapse rates. 1-year OS and DFS were significantly better for low/intermediate TERS 83% and 75% compared to high TERS 63% and 55% (p Figure 1: Survival and Relapse Estimates Based on TERS score Disclosures No relevant conflicts of interest to declare.

The immune system acting via cancer immune-surveillance is considered a potential target for improving outcomes among some malignancies. The ability to harness immune cells, engineer them and educate them to target cancer cells has changed the paradigm for treating non-Hodgkin’s lymphomas (NHL) and acute lymphoblastic leukemia (ALL). Chimeric antigen receptor (CAR) T-cell therapy has shown remarkable anti-tumor activity against refractory B cell malignancies. Ongoing research aims to expand the scope of this adoptive cell therapy, understanding mechanisms of resistance and reducing toxicity. In this review, we will discuss the current scope of CAR T-cell therapy and ongoing future applications.

Allogeneic hematopoietic cell transplantation (alloHCT) is considered the most potent postremission antileukemic therapy in adults with acute leukemia. We analyzed 172 consecutive acute leukemia patients transplanted in complete remission after a T cell-replete alloHCT from either a matched related (MRD, n = 54), unrelated (MUD, n = 67), or haploidentical (haplo, n = 51) donor to look for patient-, disease-, and transplant-related factors associated with post-transplant outcomes. Patients included 123 acute myeloid leukemia patients (first complete remission [CR], n = 94; second CR, n = 28; third CR, n = 1) and 49 acute lymphoblastic leukemia (ALL) patients (first CR, n = 39; second CR, n = 9; third CR, n = 1) with a median age of 50 years (range, 19 to 74). Median follow-up for surviving patients was 38 months. Cumulative incidence of nonrelapse mortality at 1 and 3 years was 6% and 17%, respectively. The estimated rates of 3-year overall survival, disease-free survival, and relapse incidence were 59%, 50%, and 33%, respectively. In multivariate analysis, risk factors for inferior survival included diagnosis of ALL, high risk disease risk index, and use of a female donor for a male recipient. Donor type (MRD, MUD, haplo) had no impact on any transplant outcome. Given the favorable outcomes associated with alloHCT in acute leukemia and lack of effect of donor type, a strong case can be made for transplanting acute leukemia patients in remission as soon as any donor becomes available.

Relapse is the main cause of treatment failure after nonmyeloablative haploidentical transplant (haplo-HSCT). In an attempt to reduce relapse, we have developed a myeloablative (MA) haplo-HSCT approach utilizing posttransplant cyclophosphamide (PT/Cy) and peripheral blood stem cells as the stem cell source. We summarize the results of two consecutive clinical trials, using a busulfan-based (n=20) and a TBI-based MA preparative regimen (n=30), and analyze a larger cohort of 64 patients receiving MA haplo-HSCT. All patients have engrafted with full donor chimerism and no late graft failures. Grade III-IV acute GVHD and moderate-severe chronic GVHD occurred in 23% and 30%, respectively. One-year NRM was 10%. Predicted three-year overall survival, disease-free survival, and relapse were 53%, 53%, and 26%, respectively, in all patients and 79%, 74%, and 9%, respectively, in patients with a low/intermediate disease risk index (DRI). In multivariate analysis, DRI was the most significant predictor of survival and relapse. Use of TBI (versus busulfan) had no significant impact on survival but was associated with significantly less BK virus-associated hemorrhagic cystitis. We contrast our results with other published reports of MA haplo-HSCT PT/Cy in the literature and attempt to define the comparative utility of MA haplo-HSCT to other methods of transplantation.

The prognosis of recipients of allogeneic hematopoietic cell transplantation (HCT) who require mechanical ventilation (MV) has historically been poor. Of 883 adults undergoing allogeneic HCT at the University of Minnesota between 1998 and 2009, 179 (20%) required MV before day 100 posttransplantation. We evaluated the outcomes of these patients to develop a prognostic index to predict the 100-day post-MV overall survival (OS) based on factors present at the time of MV. The 179 patients were divided at random into a training set (n = 119) and a validation set (n = 60). The 100-day postventilation OS was 17% for the total population. Multivariate Cox regression on the training set identified creatinine 20 × 109/L as significant predictors of better OS. Recursive partitioning classified patients with these good prognostic criteria into class A (n = 76); all other patients were classified as class B (n = 103). Among class A patients, 100-day OS was 29% in the training set and 30% in the validation set. Corresponding OS in class B patients was 5% and 15%, respectively. This prognostic index should help guide physicians in counseling HCT patients and their families regarding the use of MV and potential outcomes.

Allogeneic hematopoietic cell transplantation (HSCT) is considered a curative treatment for acute myelogenous leukemia (AML). Extramedullary relapse after HSCT for AML is a rare event and is less well defined than systemic, hematologic relapse. We retrospectively studied all patients with AML (n = 436) who underwent HSCT at the University of Minnesota between 1996 and 2008 who developed either a bone marrow (BM) or extramedullary (EM) relapse, and examined the incidence and risk factors for BM and EM relapse. Of 128 patients who relapsed post-HSCT, 25 had relapse in EM sites, either isolated (n = 13) or with concurrent BM relapse (n = 12). Relapse sites included bone (n = 1), central nervous system (n = 6), gastrointestinal (n = 4), lymphatic (n = 4), skin (n = 5), genitourinary (n = 1), pulmonary (n = 1), and soft tissue (n = 3). The time to relapse was longer in the EM sites (median, 328 days vs 168 days). Patients with EM relapse were more likely to have had preceding acute graft-versus-host disease (GVHD) (77% vs 49%; P = .03) or chronic GVHD (46% vs 15%; P = .02) compared with those with BM relapse. The 6-month survival postrelapse was significantly better in patients with isolated EM relapse (69%) compared with those with combined EM and BM relapse (8%) or those with BM relapse alone (27%) (P < .01). Compared with local therapy alone, systemic therapy yielded better 6-month survival in patients with EM relapse. This study suggests differing pathogenesis of BM relapse versus EM relapse of AML after allogeneic HSCT. GVHD and its accompanying graft-versus-leukemia effect may better protect BM sites, but patients with EM relapse have better responses to combined therapy and improved survival compared with those with BM relapse.

Relapse remains a major cause of mortality among patients receiving allogeneic hematopoietic cell transplantation (HCT). The impact of donor type on post-relapse survival (PRS) has not been widely examined. We compared the survival outcomes for patients relapsing after haploidentical donor transplantation (HIDT) using post-transplant cyclophosphamide with those relapsing after matched-related donor transplantation (MRDT) or matched-unrelated donor transplantation (MUDT) at our institution. Two hundred and thirty-seven consecutive HCT recipients with relapse occurring after HIDT (N=48), MUDT (N=87) and MRDT (N=102) were included in this analysis. Median age was 49 years (19-77 years) and the median time to relapse was 156 days (12-2465) after HCT. HIDT recipients had similar median time to relapse (5.8 vs 4.8 vs 5.5 months, P=0.638) compared with MUDT and MRDT, respectively. One-year PRS was worse among HIDT recipients compared with MRDT and MUDT (17% vs 46% vs 40%, P0.05). In a multivariate analysis, time to relapse (3 vs3 months post transplant), no use of donor lymphocyte infusion (DLI) following relapse, higher Dana Farber disease risk index and HCT comorbidity index scores at the time of transplant and delayed platelet engraftment post transplant were all predictive of worse PRS. This analysis shows that 1-year PRS is inferior among HIDT when compared with MRDT or MUDT. Lower use of DLI after HIDT may have contributed to this inferior survival.

Posterior reversible encephalopathy syndrome (PRES) is characterized by a group of central nervous system related symptoms. Diagnosis is usually made by computed tomography or magnetic resonance imaging. Common causes can be arterial hypertension, sepsis, autoimmune disorders, and medications. We report PRES in a relapsed Hodgkin’s Lymphoma patient after a dose of pembrolizumab.

Introduction: CD19, a B-cell surface antigen, is overexpressed in neoplastic lymphoid cells. ADCT-402 (loncastuximab tesirine; Lonca-T) is an antibody drug conjugate comprising a humanized monoclonal antibody directed against human CD19 conjugated through a pyrrolobenzodiazepine dimer toxin. This first-in-human clinical study evaluated the safety and efficacy of Lonca-T in patients (pts) with relapsed/refractory (R/R) B-cell lineage non-Hodgkin lymphoma. In the United States, follicular lymphoma (FL) is the most common indolent lymphoma and constitutes approximately 20% of all lymphomas, while mantle cell lymphoma (MCL) is rare and represents approximately 5% of all lymphomas. Here we present interim results in a subgroup of pts with FL and MCL; interim safety and efficacy of Lonca-T in pts with diffuse large B-cell lymphoma is presented in a separate abstract. Methods: Pts (≥18 years of age) with R/R FL and MCL who have failed or are intolerant to established therapies, or have no other treatment options available, were enrolled in this Phase 1, multicenter, open-label, and single-arm study including dose-escalation and dose-expansion parts. The primary objectives are to evaluate the safety and tolerability of Lonca-T, and determine the recommended dose(s) to use for expansion cohorts. The secondary objectives are to evaluate the clinical activity (measured by overall response rate [ORR], duration of response [DoR], progression-free survival [PFS] and overall survival), pharmacokinetics, pharmacodynamics, and anti-drug antibody activity. Pts received 1-hour intravenous infusions of Lonca-T every 3 weeks (Q3W; 1 cycle), with a 3+3 dose-escalation study design. No intra-pt dose-escalation is allowed. Results: As of June 20, 2018, 15 pts with FL (12 male, 3 female) and 15 with MCL (4 male, 11 female) had been enrolled in the study. The median ages of pts with FL and MCL were 58 years [range 40-75] and 64 years [range 51-87], respectively. Pts with FL had received a median 4 previous therapies (range 1-9), and those with MCL had received a median 4 prior therapies (range 1-13; Table), including prior ibrutinib therapy in 2/15 (13.3%) and 10/15 (66.7%) pts, respectively. Pts received doses of Lonca-T ranging from 15 to 200 µg/kg Q3W (FL, median cycles: 3 [range 2-11] and MCL, median cycles: 2 [range 1-11]). Of all pts with FL or MCL, treatment-emergent adverse events (TEAEs) were reported in 29/30 (96.7%) pts, and grade ≥3 TEAEs in 20 (66.7%) pts. The most common all-grade TEAEs (≥20% pts), regardless of relationship to study treatment, were fatigue (13 [43.3%]), increased gamma-glutamyltransferase (GGT) (13 [43.3%]), anemia (10 [33.3%]), myalgia (9 [30.0%]), increased alkaline phosphatase (8 [26.7%]), dyspnea (8 [26.7%]), nausea (8 [26.7%]), peripheral edema (8 [26.7%]), pleural effusion (8 [26.7%]), abdominal pain (7 [23.3%]), erythema (7 [23.3%]), decreased neutrophil count (7 [23.3%]), increased alanine transferase (6 [20.0]), increased aspartate aminotransferase (6 [20]), constipation (6 [20.0]), decreased appetite (6 [20.0]), and headache (6 [20.0]). The most common grade ≥3 TEAEs (>10% pts) were increased GGT (8 [26.7%]), decreased neutrophil count (6 [20.0%]), and anemia (4 [13.3%] pts). The figure depicts tumor response data for pts with FL and MCL. For the 15 evaluable pts with FL, the ORR was 80% (12/15 pts), comprising 8/15 (53.3%) complete responses (CRs) and 4/15 (26.7%) partial responses (PRs). The median DoR and PFS (responders and non-responders) were not reached in pts with FL after a median follow-up time of 7.56 months. Out of 15 evaluable pts with MCL, the ORR was 7/15 (46.7%), comprising 4/15 (26.7%) CRs and 3/15 (20.0%) PRs. In pts with MCL, median DoR was 5.3 months and PFS was 4.8 months after a median follow-up time of 5.78 months. Conclusions: In this Phase 1 study, Lonca-T has demonstrated encouraging single-agent antitumor activity and manageable toxicity in pts with R/R FL and MCL. Study sponsored by ADC Therapeutics. http://clinicaltrials.gov/show/NCT02669017. Figure. Figure. Disclosures Caimi: Genentech: Membership on an entity's Board of Directors or advisory committees; ADC Therapeutics: Research Funding; Kite Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees; Celgene: Speakers Bureau. Kahl:Genentech: Consultancy; Seattle Genetics: Consultancy; ADC Therapeutics: Research Funding. Hamadani:Merck: Research Funding; ADC Therapeutics: Research Funding; Sanofi Genzyme: Research Funding, Speakers Bureau; Janssen: Consultancy; Takeda: Research Funding; Cellerant: Consultancy; Celgene Corporation: Consultancy; MedImmune: Consultancy, Research Funding; Ostuka: Research Funding. Carlo-Stella:Rhizen Pharmaceuticals: Research Funding; Sanofi: Consultancy; Boehringher Ingelheim Italia: Consultancy; MSD Italia: Speakers Bureau; Genenta Science: Speakers Bureau; AstraZeneca: Speakers Bureau; Amgen: Speakers Bureau; Bristol-Myers Squibb: Speakers Bureau; Janssen: Speakers Bureau; ADC Therapeutics: Research Funding, Speakers Bureau. He:ADC Therapeutics: Employment, Equity Ownership. Ungar:ADC Therapeutics: Employment, Equity Ownership. Feingold:ADC Therapeutics: Employment, Equity Ownership. Ardeshna:Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, Accommodations, Expenses; ADC Therapeutics: Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, Accommodations, Expenses; Roche: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, Accommodations, Expenses; Roche: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, Accommodations, Expenses; Takeda: Membership on an entity's Board of Directors or advisory committees; Takeda: Membership on an entity's Board of Directors or advisory committees; ADC Therapeutics: Membership on an entity's Board of Directors or advisory committees, Research Funding. Radford:ADC Therapeutics: Consultancy, Research Funding; Seattle Genetics: Consultancy, Speakers Bureau; Celgene: Research Funding; BMS: Consultancy, Speakers Bureau; Takeda: Consultancy, Research Funding, Speakers Bureau; AstraZeneca: Equity Ownership; GlaxoSmithKline: Equity Ownership; Novartis: Consultancy, Speakers Bureau; Pfizer: Research Funding. Solh:Celgene: Speakers Bureau; ADC Therapeutics: Research Funding; Amgen: Speakers Bureau. Heffner:Kite Pharmaceuticals: Research Funding; ADC Therapeutics: Research Funding; Genentech: Research Funding; Pharmacyclics: Research Funding. O'Connor:ADC Therapeutics: Research Funding; Celgene: Research Funding; Seattle Genetics: Research Funding.

The median age of acute myeloid leukemia (AML) diagnosis is 69 years with 60% of newly diagnosed patients > 60 years. Due to a perceived intolerance to therapy, many elderly AML patients do not receive therapy. Of those that do, few are eligible for curative intent therapy with hematopoietic stem cell transplantation (HSCT) due to perceived lack of fitness, excessive comorbidity or absence of a donor. To better understand the outcomes of elderly AML patients, we evaluated a cohort of 323 consecutive elderly AML patients (≥60 years) referred to the Leukemia Program at Northside Hospital from January 2009 to December 2017 for evaluation and management. Our treatment algorithm is to offer intensive chemotherapy (IC) to all potentially eligible patients and HSCT to all transplant-eligible non-favorable risk patients that achieve complete remission, with or without complete platelet recovery (CR1(p)). Median patient age was 70 years (range 60-88). AML occurred de novo in 218 (67%), therapy-related in 33 (10%) and secondary in 72 (22%) patients. NCCN risk category was favorable (fav) in 48 (15%), intermediate (int) in 112 (35%) and poor in 161 (50%). Leukemia induction therapy, either IC (n=204) or hypomethylating agents (HMA, n=58), was given to all but 61 (19%) patients (IC - 78%, HMA - 22%). Of patients receiving IC, the major regimens were FLAG+/-Ida (n=117), 7+3 (n=58) and CPX-351 (n=18). Of the IC/HMA-treated patients (n=262), 130 (50%) achieved CR1(p) with the first induction, while 158 (60%) ultimately achieved CR1(p). In patients with fav, int and poor risk AML, CR1(p) was achieved in 73%, 52% and 41% respectively. HSCT was performed on 63 patients (59 - int/poor risk, 4- fav risk): autologous [5], matched sibling donor [21], matched unrelated donor [24], haploidentical donor [13]. Of the non-fav risk AML CR1(p) patients, where the treatment goal is HSCT if feasible, 57 (46%) of 124 received HSCT. After a median f/u of 34 months, 2-year overall survival (OS) for the whole cohort was 31%; corresponding rates for fav, int and poor risk AML was 58%, 35% and 20% respectively. Survival was similar in patients aged 60-66 and 67-72 years (2-yr OS 35% and 38%), but superior to those in the 73-88 yr tertile (2-yr OS 19%, p Disclosures Solh: Celgene: Speakers Bureau; Amgen: Speakers Bureau; ADC Therapeutics: Research Funding.

Post-transplant cyclophosphamide (PTCy) has improved the outcomes and expanded the use of haploidentical hematopoietic cell transplantation (haplo-HCT). Unlike many other allogeneic HCT settings, the impact of HLA disparity on graft-versus-host disease (GVHD) and transplant outcome in this setting remains unclear. HLAMatchmaker is a computer algorithm that assesses HLA compatibility at the structural level by determining what and how many functional epitopes (eplets), defined as patches of polymorphic residues within a radius of 3.0-3.5 Ångstroms, are shared between donor and recipient. It has been useful in the identification of acceptable mismatches (mm) for alloimmunized kidney transplant candidates. In order to determine the effects of HLA class I (HLA-A, B, C) and II (HLA-DR, DQ, DP) epitope mm on transplant outcome, we retrospectively analyzed 208 consecutive donor-recipient pairs receiving haplo-HCT with PTCy for hematologic malignancy. The impact of epitope mm (GVH direction) on GVHD and survival endpoints was evaluated by Cox multivariate analysis (MVA), controlling for other significant patient, donor and transplant-related factors. Median (range) recipient and donor age was 52 (19-75) and 38 (15-73) years respectively. Patients were transplanted for AML (34%), MDS/MPS/CML (20%), ALL (17%), NHL/HD/CLL (25%). PBSC was used as the stem cell source in 66% of patients, and conditioning intensity was myeloablative in 41%. The donor was a child, sibling, or parent in 47%, 38%, and 14% respectively. Median (range) follow-up for surviving patients was 33 (7-130) months. HLA class I epitope mm had no effect on GVHD or survival. In contrast, increased HLA class II epitope mm (>16) was significantly correlated to an increased frequency of chronic GVHD (figure 1). In MVA, higher degree of class II epitope mm was associated with chronic GVHD, total (HR 1.91, p=0.012) and moderate-to-severe (HR 2.37, p=0.006). The positive effect of increased class II epitope mm on chronic GVHD was driven mostly by HLA-DQ epitope mm (HR 1.7 for >7 vs. ≤7, p=0.047) with a non-significant contribution from HLA-DP (HR 1.36 for >2 vs. ≤2, p=0.24). In contrast, increased HLA-DR epitope mm had a protective effect on chronic GVHD (HR 0.52 for >7 vs. ≤7, p=0.021). Epitope mm was not significantly associated with acute GVHD, grade 2-4 or 3-4. There was also no effect of allele-level mm at any HLA loci on acute or chronic GVHD. We next tested the impact of class I and II epitope mm on survival, including the individual impact of HLA-DR, -DQ and -DP epitope mm. Although class I epitope mm had no impact in univariate analysis, a higher number of class II epitope mm (>16) was correlated with better overall survival and the effect was primarily driven by HLA-DQ epitope mm (figure 2). To better assess the impact of class II epitope mm on survival, we analyzed this variable in the context of a previously published MVA (Solomon et al. Biol Blood Marrow Transplant. 2018;24:789-798). Controlling for other significant variables (age, race, CMV status, donor relationship, HLA-DR mm, nonpermissive HLA-DP mm, KIR receptor-ligand mm and KIR haplotype), only increased HLA-DQ epitope mm (>7) was independently associated with decreased non-relapse (HR 0.34, p=0.021) and overall mortality (HR 0.60, p=0.039). These results indicate a significant effect of class II epitope mm on chronic GVHD and survival following haplo-HCT with PTCy. Higher level of class II epitope mm and HLA-DQ epitope mm is associated with increased chronic GVHD incidence, whereas HLA-DR epitope mm is protective. Higher HLA-DQ epitope mm is independently associated with better survival, when controlling for the presence of HLA-DR allele-level mm or a nonpermissive HLA-DP mm, which have been shown previously to improve survival. Class II HLA epitope level matching provides important prognostic information in the setting of haplo-HCT and PTCy, which is not reflected by conventional allele-level matching. Disclosures Solh: Amgen: Speakers Bureau; Celgene: Speakers Bureau; ADC Therapeutics: Research Funding.

Background: Induction chemotherapy (7+3) or high-dose ara-C-based (HIDAC) for AML results in prolonged neutropenia with a high risk of serious infection and attendant morbidity, and prolonged hospitalization. Romyelocel-L is a human off-the-shelf allogeneic myeloid progenitor cell (MPC) preparation manufactured by ex vivo culture expansion of CD34+ cells. Following infusion, MPCs are expected to home to bone marrow (BM) and produce neutrophils. In a randomized, open-label, controlled Phase 2 trial, the effect of romyelocel-L was studied in de novo patients receiving HIDAC or 7+3 induction therapy for reduction of fever and infection. The results from pooled and 7+3 cohorts, were previously presented, showing decrease in infections and days in hospital. The results from cohorts receiving HIDAC chemotherapy are presented here. Methods: 53 subjects with de novo AML (age ≥55) and receiving HIDAC induction were randomized on Day 0 (first day of induction) to receive either romyelocel-L (7.5x106 cells/kg) on Day 9 + GCSF qd starting on Day 14 (treatment) or GCSF alone starting on Day 14 (control) qd until ANC recovery to 500/µL. Of the 53 subjects, 42 were considered evaluable (20 in treatment and 22 in control) which meant that they received romyelocel-L + GCSF or GCSF alone, were in study ≥ 28 days and did not receive additional chemotherapy before Day 28. Subjects routinely received corticosteroids concurrently with HIDAC induction. Most patients received prophylactic antibacterial (74%) and antifungal (86%) agents. Endpoints assessed from Day 9 to Day 28 included days in a Febrile Episode (DFE, primary endpoint) and microbiologically defined bacterial or fungal infections (MDI, defined as an infection when a specific pathogen is identified)/clinically diagnosed infections (CDI, defined when there is supporting clinical, laboratory, and/or radiologic data that is sufficient to indicate an infection and no specific pathogen is identified). MDIs and CDIs were adjudicated by a blinded independent committee. The number of days in hospital was assessed through Day 42. Data are reported for 2 periods: from infusion of romyelocel-L (Day 9-28) and from 6 days after infusion of romyelocel-L (1 day after start of GCSF) - Day 28 (denoted as Day 15-28; the period when romyelocel-L derived neutrophils are likely to be circulating.). One-sided p-values are reported. Results: The baseline characteristics, including median age, mean WBC, and ECOG status were balanced between the treatment and control groups. The mean DFE during Day 9-28 in the treatment and control was 6.00 and 4.04 days respectively. Absence of fever was seen in 0/20 and 9/22 (40.9%) in the treatment and control group, respectively. The mean DFE for Day 15-28 was 1.37 and 2.98 days in the treatment vs. control respectively. The incidence of MDI or CDI during Day 9-28 was 40% vs 41% in the treatment vs. control, however a significant decrease was observed during Day 15-28 with incidence of 5% vs 27.3% in the treatment vs control (p=0.027). The use of prophylactic antimicrobial agents was similar between study arms. Mean number of days in hospital were 22.6 vs 25.7 days in treatment vs. control groups (p=0.027). The median number of days to ANC recovery of 500/µl was 19.5 vs 21.5 days in treatment vs control (p=0.103). Remission rates were similar in the two groups. All seven subjects assessed for chimerism had romyelocel-L cells detected in peripheral blood (PB) on the day of infusion. Post infusion, chimerism was observed in 6/7 subjects in one or more of BM, peripheral blood and gingival rinse samples. No deaths were observed in either of the two arms within the first 42 days. Romyelocel-L was generally tolerated well. Summary/Conclusion: The incidence of infections was decreased during the day 15-28 period and a decrease of three days in hospital stay was observed in de novo HIDAC AML subjects receiving romyelocel-L. Romyelocel-L may provide a new option to reduce infections in AML patients undergoing HIDAC induction therapy. Disclosures Ravandi: Macrogenix: Honoraria, Research Funding; Xencor: Research Funding; Abbvie: Research Funding; Seattle Genetics: Research Funding; Astellas Pharmaceuticals: Consultancy, Honoraria; Sunesis: Honoraria; Xencor: Research Funding; Bristol-Myers Squibb: Research Funding; Sunesis: Honoraria; Abbvie: Research Funding; Amgen: Honoraria, Research Funding, Speakers Bureau; Bristol-Myers Squibb: Research Funding; Amgen: Honoraria, Research Funding, Speakers Bureau; Macrogenix: Honoraria, Research Funding; Astellas Pharmaceuticals: Consultancy, Honoraria; Seattle Genetics: Research Funding; Orsenix: Honoraria; Jazz: Honoraria; Orsenix: Honoraria; Jazz: Honoraria. Abboud:Jazz: Honoraria, Speakers Bureau; Agios: Honoraria. Akard:Bristol-Myers Squibb: Speakers Bureau; Novartis: Speakers Bureau; Takeda: Speakers Bureau; Celgene: Speakers Bureau; Gilead: Speakers Bureau. Gill:Extellia: Consultancy, Membership on an entity's Board of Directors or advisory committees; Carisma Therapeutics: Equity Ownership; Novartis: Research Funding. Khan:Teva: Speakers Bureau. Stock:Jazz Pharmaceuticals: Consultancy. Brown:Cidara Therapeutics: Consultancy. DiNardo:Abbvie: Honoraria; Karyopharm: Honoraria; Agios: Consultancy; Medimmune: Honoraria; Bayer: Honoraria; Celgene: Honoraria. Kadia:BMS: Research Funding; Amgen: Consultancy, Research Funding; Novartis: Consultancy; Amgen: Consultancy, Research Funding; Novartis: Consultancy; Takeda: Consultancy; Jazz: Consultancy, Research Funding; Pfizer: Consultancy, Research Funding; Takeda: Consultancy; Abbvie: Consultancy; Abbvie: Consultancy; Celgene: Research Funding; Celgene: Research Funding; Jazz: Consultancy, Research Funding; BMS: Research Funding; Pfizer: Consultancy, Research Funding. Mamelok:Cellerant Therapeutics, Inc.: Consultancy, Employment. Panuganti:Cellerant Therapeutics, Inc.: Employment. Van Syoc:Cellerant Therapeutics, Inc.: Employment. Wong:Cellerant Therapeutics, Inc.: Employment. Zimmerman:Cellerant Therapeutics, Inc.: Employment. Solh:Amgen: Speakers Bureau; ADC Therapeutics: Research Funding; Celgene: Speakers Bureau.

Introduction: Diffuse large B-cell lymphoma (DLBCL) represents 33% of the non-Hodgkin lymphomas (NHL) and expresses CD19, a classic B-cell marker found on B lymphocytes. ADCT-402 (loncastuximab tesirine; Lonca-T) is an antibody drug conjugate comprising a humanized antibody directed against human CD19 conjugated to a pyrrolobenzodiazepine dimer toxin. This first-in-human clinical study evaluated the safety and efficacy of Lonca-T in patients (pts) with relapsed/refractory (R/R) B-cell lineage NHL. Here we present interim results in the subgroup of pts with DLBCL. Interim efficacy and safety of Lonca-T in pts with follicular lymphoma and mantle cell lymphoma are presented in a separate abstract. Methods: Pts ≥18 years of age with R/R DLBCL who have failed or are intolerant to established therapies, or have no other treatment options available, were enrolled in this Phase 1, multicenter, open-label, single-arm study, including dose-escalation and dose-expansion parts. The primary objectives are to evaluate the safety and tolerability of Lonca-T, and determine the recommended dose(s) to use for expansion cohorts. The secondary objectives are to evaluate the clinical activity (measured by overall response rate [ORR], duration of response [DoR], progression-free survival [PFS] and overall survival [OS]), pharmacokinetics, pharmacodynamics, and anti-drug antibody activity. Pts receive 1-hour intravenous infusions of Lonca-T every 3 weeks (1 cycle), with a 3+3 dose-escalation design for the dose-escalation part of the study. No intra-pt dose escalation is allowed. Results: As of June 20, 2018, 183 pts had been enrolled on the study, including 137 with DLBCL (79 male, 58 female). Pts with DLBCL had a median age of 63 years [range 20-86], and had received a median of 3 previous therapies (range 1-10; Table). Pts received doses of Lonca-T ranging from 15 to 200 µg/kg (median cycles: 2 [range 1-13]). Treatment-emergent adverse events (TEAEs) were reported in 136/137 (99.3%) pts, and grade ≥3 TEAEs in 100/137 (73.0%) pts. The most common all-grade TEAEs (≥20% pts), regardless of relationship to study treatment, were fatigue (57 [41.6%]), nausea (44 [32.1%], peripheral edema (44 [32.1%]), anemia (39 [28.5%]), rash (35 [25.5%]), gamma-glutamyltransferase (GGT) increased (33 [24.1%]), constipation (30 [21.9%]), dyspnea (29 [21.2%]), and thrombocytopenia (28 [20.4%]). The most common grade ≥3 TEAEs (>10% pts) were GGT increased (21 [15.3%]), neutropenia (20 [14.6%]), neutrophil count decreased (19 [13.9%]), anemia (15 [10.9]), thrombocytopenia (15 [10.9%]) and platelet count decreased (14 [10.2%]. Approximately 66% and 72% of pts in the 120 and 150 µg/kg groups, respectively, tolerated at least 2 cycles before any AE leading to dose reduction/delay occurred. The figure depicts tumor response data. Out of 132 evaluable pts with DLBCL, the ORR was 40.2% (53/132 pts), comprising 29/132 (22.0%) complete responses (CRs) and 24/132 (18.2%) partial responses (PRs). Median DoR was 4.17 months and PFS was 2.79 months after a median follow-up of 5.13 months. Median DoR was not reached in pts achieving a CR and was 2.76 months in pts with a PR. In pts with non-bulky disease, the ORR was 44.2% (50/113 pts); 28/113 (24.8%) pts attained a CR and 22/113 (19.5%) pts attained a PR. The majority of pts (122/132) received doses ≥120 µg/kg; in these pts, the ORR was 41.8% (51/122 pts), with 28/122 (23.0%) pts attaining a CR and 23/122 (18.9%) pts attaining a PR. Conclusions: In this Phase 1 study, Lonca-T has demonstrated encouraging and durable single-agent antitumor activity and manageable toxicity in pts with R/R DLBCL at doses ≥120 µg/kg. Updated safety, tolerability, and efficacy results will be presented at the meeting. Study sponsored by ADC Therapeutics. http://clinicaltrials.gov/show/NCT02669017. Disclosures Radford: Pfizer: Research Funding; ADC Therapeutics: Consultancy, Research Funding; BMS: Consultancy, Speakers Bureau; GlaxoSmithKline: Equity Ownership; Seattle Genetics: Consultancy, Speakers Bureau; Takeda: Consultancy, Research Funding, Speakers Bureau; AstraZeneca: Equity Ownership; Novartis: Consultancy, Speakers Bureau; Celgene: Research Funding. Kahl:Seattle Genetics: Consultancy; Genentech: Consultancy; ADC Therapeutics: Research Funding. Hamadani:Sanofi Genzyme: Research Funding, Speakers Bureau; Takeda: Research Funding; Cellerant: Consultancy; Ostuka: Research Funding; MedImmune: Consultancy, Research Funding; ADC Therapeutics: Research Funding; Janssen: Consultancy; Celgene Corporation: Consultancy; Merck: Research Funding. Carlo-Stella:Boehringher Ingelheim Italia: Consultancy; Bristol-Myers Squibb: Speakers Bureau; Sanofi: Consultancy; MSD Italia: Speakers Bureau; Rhizen Pharmaceuticals: Research Funding; Genenta Science: Speakers Bureau; Janssen: Speakers Bureau; AstraZeneca: Speakers Bureau; Amgen: Speakers Bureau; ADC Therapeutics: Research Funding, Speakers Bureau. Caimi:Genentech: Membership on an entity's Board of Directors or advisory committees; ADC Therapeutics: Research Funding; Celgene: Speakers Bureau; Kite Pharma: Membership on an entity's Board of Directors or advisory committees. Ardeshna:Roche: Membership on an entity's Board of Directors or advisory committees, Other: Conference expenses, Research Funding; Celgene: Membership on an entity's Board of Directors or advisory committees; ADC Therapeutics: 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. Feingold:ADC Therapeutics: Employment, Equity Ownership. He:ADC Therapeutics: Employment, Equity Ownership. Reid:AbbVie: Research Funding; Millenium Pharmaceuticals: Research Funding; ADC Therapeutics: Research Funding. Solh:ADC Therapeutics: Research Funding; Celgene: Speakers Bureau; Amgen: Speakers Bureau. Chung:ADC Therapeutics: Research Funding. Heffner:Pharmacyclics: Research Funding; ADC Therapeutics: Research Funding; Kite Pharma: Research Funding; Genentech: Research Funding. Ungar:ADC Therapeutics: Employment, Equity Ownership. O'Connor:ADC Therapeutics: Research Funding; Seattle Genetics: Research Funding; Celgene: Research Funding.

The fludarabine, high dose cytarabine and G_CSF with or without idarubicin combination regimen, referred to as FLAG+/-Ida, is commonly used as a salvage regimen for relapsed/refractory AML but its use as initial induction therapy has been more limited. The MRC trial 15 compared 2 induction courses of FLAG-Ida regimen to 3+7 (anthracycline plus cytarabine) regimens with etoposide (ADE) and found a higher relapse free survival among patients receiving FLAG-Ida. The findings of the MRC AML 15 trial are not widely applied in the United States as many experts use one course of induction followed by consolidation if patients achieve remission. The impact of choice of induction regimen on post remission survival in non-favorable risk AML patients remains unclear. To address this question, we assessed outcomes of 306 consecutive AML patients between aged 18 to75 years, with non-favorable NCCN risk who were received initial treatment at our center between January of 2009 and July of 2017 with either 3+7 (n=88) or FLAG+/-Ida (n=218). Our center's algorithm is to offer allogeneic HSCT as a consolidative therapy to all AML patients with non-favorable risk in CR1 who are considered transplant candidates. Patient characteristics were as follows: Median age 58(19, 75), male 55%, FLT-3 ITD positive 12%, NCCN risk ( intermediate 49%, poor 51%) and normal cytogenetics 45%. Baseline characteristics were similar between the two treatment groups with FLAG+/-Ida being younger at time of diagnosis (59 vs 66 years, P Disclosures Solh: Amgen: Speakers Bureau; Celgene: Speakers Bureau; ADC Therapeutics: Research Funding.

Haploidentical donor (HID) transplant with post-transplant cyclophosphamide (PTCy) is being increasingly utilized worldwide. Although the original "Baltimore" protocol employed nonmyeloablative conditioning, there has been increasing interest in the use of myeloablative conditioning (MAC) in an attempt to decrease the risk of disease recurrence and graft failure. We present the long-term follow-up results of 82 consecutive patients receiving a MAC HID transplant at a single institution between 2011-2017, following a uniform protocol of Fludarabine/total body irradiation (TBI) 1200cGy conditioning, PTCy, tacrolimus and mycophenolate mofetil. PBSC was utilized as the graft source for all transplants and graft CD34 dose was capped at 5 x 106/kg. Median patient age was 42 (range 19-61) years. The most common diagnoses were AML (51%) and ALL (33%), and 39% were high/very high disease risk index (DRI). Donor was a child, sibling or parent in 35%, 43% and 22% respectively. Median follow-up time for surviving patients was 37 months. Primary engraftment occurred in all patients, with all patients achieving complete donor T cell and myeloid chimerism by day +30. There were no cases of late graft failure. The cumulative incidence of grade 3-4 acute graft-versus-host disease (GVHD) and moderate-to-severe chronic GVHD was 17% and 22%, respectively. Non-relapse mortality (NRM) was 7% at one year and 12% at three years post-transplant. Overall survival at 1, 2, and 3 years post-transplant was 85%, 72% and 66% respectively (figure 1). Estimated 3-year DFS, current GVHD-, relapse-free survival (CGRFS), conventional GRFS, and relapse was 67%, 62%, 43%, and 21% respectively. DFS at 3-yr was significantly improved in patients with low/intermediate vs high/very high DRI (79% vs. 48%, figure 2) due to a lower risk of relapse (12% vs. 36%). Infectious complications included CMV reactivation in 55% of patients (CMV disease - 2%) and BK virus infection in 38% (severe - 2%). There were no reported cases of EBV lymphoproliferative disease. This large single institution analysis with long-term follow-up confirms the feasibility of Fludarabine/TBI-based MAC HID transplant with PBSC/PTCy in younger adult patients. This is supported by both the high rate of engraftment, low NRM and a 3-yr CGRFS of 62% (suggesting freedom from relapse and need for long-term systemic immunosuppression for GVHD). The achievement of long term DFS in approximately 80% of low/intermediate DRI and half of high/very high DRI patients is promising. Disclosures Solh: ADC Therapeutics: Research Funding; Celgene: Speakers Bureau; Amgen: Speakers Bureau.

Patients with intermediate and poor risk AML have unsatisfactory outcomes with conventional chemotherapy-based treatment. Allogeneic HSCT offers the best chance of long-term survival for patients who achieve complete remission (CR) and are eligible for such a procedure. There are several potential barriers to receiving an allogeneic HSCT, including but not limited to: achieving CR, timely referral to a transplant center, identifying a donor, and performing the HSCT prior to relapse or significant complications arising from induction and consolidation therapy. To better understand the outcomes of young, newly diagnosed non-favorable risk AML patients, we evaluated 271 consecutive adult patients (age ≤65 years) referred to our center between January of 2009 and July of 2017 for management. Patients were treated in an integrated acute leukemia and transplant management unit and it is our policy to offer intensive chemotherapy to all potentially eligible patients and HSCT to all transplant-eligible, non-favorable risk AML patients that achieve CR, with or without complete blood count recovery. Patient characteristics were as follows: Median age 55 (19, 65) years, male sex 50%, NCCN risk (intermediate 51%, poor 49%), FLT 3 ITD positive 15% and normal cytogenetics in 39%. Remission induction chemotherapy was given to 262patients with FLAG+/-IDA being the most commonly used regimen in 161 patients (61%) followed by 3+7 in 63 (24%)patients. Following induction, 211 (81%) achieved a CR1 after one (n=178), two (n=26) or three (n=7) courses of induction with a median follow up for survivors of 44.5 months. For patients with intermediate and poor risk NCCN categories, CR was achieved in 86% and 73% respectively. HSCT was performed on 146 (69%) patients (NCCN intermediate risk n=83, poor risk n=63): Myeloablative conditioning n=103 (71%), autologous (n=10), matched related donor (n=45), matched unrelated donor (n=51) and haploidentical mismatched related donor (n=40). Of the 65 patients in CR1 who did not receive HSCT, the reasons for not receiving HSCT were as follows: relapse prior to transplant (n=23), lack of psychosocial support (n=14), persistent active infection or organ dysfunction (n=16) at time of transplant evaluation, patient declined transplant (n=7) and poor performance status post induction (n=5). The 3 year estimates for OS and DFS were 50% and 44% respectively. Patients who received HSCT had a better 3 year OS and DFS of 59% and 52% compared to 27% and 27% for patients not receiving HSCT (p Disclosures Solh: Amgen: Speakers Bureau; Celgene: Speakers Bureau; ADC Therapeutics: Research Funding.

Lack of a matched sibling or unrelated donor can be a significant barrier to allogeneic hematopoietic cell transplantation (HCT). Haploidentical (haplo) donors are readily available for nearly all such patients. However, donor selection criteria to determine the optimal haplo donor are not readily available. In order to determine which donor characteristics are most important in predicting transplant success, we retrospectively analyzed 208 consecutive donor-recipient pairs receiving haplo HCT with post-transplant cyclophosphamide for hematologic malignancy. Donor characteristics were evaluated by multivariate Cox analysis and correlated with overall survival (OS), disease-free survival (DFS), relapse/progression, and non-relapse mortality (NRM), while controlling for significant patient and transplant-related factors. Donor variables analyzed included age, sex, relationship to recipient, CMV status, ABO compatibility, HLA disparity and several NK alloreactivity models (KIR receptor-ligand, ligand-ligand, haplotype, B content, activating KIR-based education systems, Sekine donor licensing model). Median (range) recipient and donor age was 52 (19-75) and 38 (15-73) years respectively, and 41% of donor-recipient pairs were non-Caucasian. Patients were transplanted for AML (34%), MDS/MPS/CML (20%), ALL (17%), NHL/HD/CLL (25%). PBSC was used as the stem cell source in 66% of patients, and conditioning intensity was myeloablative in 41%. The donor was a child, sibling, or parent in 47%, 38%, and 14% respectively. Median (range) follow-up for surviving patients was 33 (7-130) months. In multivariate Cox analysis, patient/transplant characteristics associated with improved OS and DFS included recipient age Disclosures Solh: ADC Therapeutics: Research Funding; Amgen: Speakers Bureau; Celgene: Speakers Bureau.

CD20 is a transmembrane protein expressed on mature B cells through all stages of their development. However, its expression is down-regulated at the point of differentiation into plasma cells, and...

The impact of initial fludarabine therapy on transformation to Richter syndrome (RS) or prolymphocytic leukemia (PLL) in patients with chronic lymphocytic leukemia (CLL) is uncertain. We studied the outcomes of 521 patients with CLL who were randomized to initial fludarabine (F), chlorambucil (C) or F + C therapy on an intergroup trial (CALGB 9011). RS developed in 34 (7%) patients and PLL in 10 (2%). RS and PLL occurred in 14 (7%) and three (2%) of 188 patients randomized to F; nine (5%) and four (2%) of 191 patients treated with C; and 11 (8%) and three (2%) of 142 receiving F + C, respectively. Four percent of the 206 patients with Rai stage III/IV developed PLL, compared to only 1% of the 315 patients with Rai stage I/II (p = 0.02). Initial fludarabine therapy in patients with CLL did not impact transformation to RS or PLL, nor were any other baseline characteristics predictive for such transformation in this series.

Hepatosplenic T-cell lymphoma is a rare and aggressive peripheral T-cell malignancy that is distinctively characterized by sinusoidal infiltration of mature medium-sized T lymphocytes in the spleen and liver. The neoplastic cells are classically surface CD3+, CD2+, CD5−, CD4−, and CD8+/− and manifest variable expression of markers associated with natural killer (NK) cells such as CD16 and CD56. In this article, we report the first case to date of a newly diagnosed de novo surface CD3− hepatosplenic T-cell lymphoma with circulating blastlike neoplastic cells expressing NK-cell–associated markers. The lack of surface CD3 expression, together with the expression of NK-cell–associated markers and the leukemic presentation, leads to significant diagnostic challenges in differentiating this CD3− hepatosplenic T-cell lymphoma from NK-cell neoplasms, in particular aggressive NK-cell leukemia. The related literature is reviewed, and the approaches for adequate diagnosis of this novel situation are described.

T cell-replete haploidentical donor transplants (HAPLO-HCT) using post-transplant cyclophosphamide for control of alloreactivity is now being increasingly utilized. HAPLO-HCTs were originally performed using BM grafts. However, recently, a few single center studies have reported good outcomes using G-CSF mobilized PBSC grafts for HAPLO-HCT. No prospective randomized comparisons of BM to PBSC grafts for HAPLO-HCT have been performed. Therefore, we analyzed outcomes for 687 adults (496 BM, 191 PBSC) who received HAPLO-HCT for hematologic malignancies using post-transplant cyclophosphamide + mycophenolate + calcineurin inhibitor for GVHD prophylaxis between 2009 and 2014 in the United States. The primary outcome was overall survival. The characteristics of recipients of BM and PBSC were similar except BM recipients were older, more likely to have a performance score ≥90, HCT-CI index ≤2, be CMV seronegative, have a lymphoid malignancy and receive reduced-intensity conditioning. Most PBSC transplants occurred between 2012 and 2014. The median follow-up was 35 and 20 months for recipients of BM and PBSC grafts, respectively. Cox regression models were built to study the effect of graft type adjusted for other significant factors on overall mortality, non-relapse mortality, relapse and graft-versus-host disease (GVHD) and outcomes censored at 2-years to accommodate differential follow-up between treatment groups (Table 1). After adjusting for age, CMV serostatus, disease risk index (disease type/disease status for myeloid and lymphoid malignancy and cytogenetic risk for acute leukemia and myelodysplastic syndrome) and transplant conditioning regimen there were no significant differences in risks for overall mortality (HR 1.00, p= 0.98; 2-year overall survival: 54% and 57%) or non-relapse mortality (HR 0.92, p=0.74; 2-year non-relapse mortality: 17% and 16%) after transplantation of BM compared to PBSC, respectively. However, relapse risks were higher after transplantation of BM compared to PBSC (HR 1.49, p=0.009; 2-year relapse: 45% and 28%). Subset analyses explored the effect of graft type separately for myeloablative and reduced intensity conditioning regimen adjusting for age, CMV serostatus and disease risk index. Consistent with the main analysis there were no differences in overall or non-relapse mortality risks and relapse risks were higher with BM compared to PBSC with myeloablative regimens (Table 1). Although this may in part be explained by lower chronic GVHD risks with transplantation of BM grafts, chronic GVHD was not significantly predictive of relapse risk when modeled as a time-dependent covariate (HR= 0.73, p=0.49). Grade II-IV acute GVHD risks (HR 0.45, p Table 1. Table 1. Disclosures Ciurea: Cyto-Sen Therapeutics: Equity Ownership; Spectrum Pharmaceuticals: Other: Advisory Board. Hamadani:Takeda: Research Funding. Soiffer:Kiadis: Membership on an entity's Board of Directors or advisory committees; Jazz Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees; Juno: Membership on an entity's Board of Directors or advisory committees. Wingard:Ansun: Consultancy; Gilead: Consultancy; Astellas: Consultancy; Fate Therapeutics: Consultancy; Merck: Consultancy.

Patients undergoing allogeneic hematopoietic cell transplants (Allo-HCT) using myeloablative preparative regimens are usually admitted to an inpatient transplant unit from the start of the conditioning regimen until hematopoietic recovery (on average 25-35 days). Historically, the rationale for routine inpatient care during this period has been the facilitation of administration of parenteral medications, prevention of mold infections and the monitoring and management of acute toxicities. However, advances in supportive care and other technologies may allow outpatient management during this period. We analyzed outcomes of all consecutive patients who underwent myeloablative allo-HCT as defined by the CIBMTR (Giralt 2009, BBMT) with planned total outpatient management at our center. Patient characteristics and outcome data were prospectively entered into our institutional database from which they were extracted for this analysis. Patients were scheduled to receive their conditioning regimen and post-transplant care in our purpose-built outpatient clinic. Patients received their stem cell infusion on the inpatient unit and were planned to be discharged home the same day except patients receiving haploidentical transplants who were planned to be discharged on day +5 to accommodate the early cytokine release syndrome commonly seen in such patients (Solomon BBMT 2012). Subsequent admissions were for significant complications necessitating inpatient management only. Our technical approach to total outpatient management of myeloablative allo-HCT was as previously described (Solomon BMT 2010, 45: 468-475). Patients (n=462) were transplanted consecutively between 4/08 and 12/15. Patient characteristics were: median age 46; male (53%); race - white 79%, black 18%, Asian 2%; diagnosis- AML 42%, ALL 21%, MDS/MPS 21%, NHL/HL/CLL 13%, other 3%; donor type - MRD 48%, MUD 35%, Haplo 17%, CBT 10 (18%). For readmitted patients, most frequent reasons were - febrile neutropenia 33%, mucositis 29%, and lower GI toxicity 4.5%. Median total length of inpatient stay through d+100 was 16 d (range 1-98). Fungal infections were documented in only 3 patients (1%) through d +100. With a median follow-up for surviving patients of 52 months (6-218 months), K-M estimates of survival and DFS at 1 yr are 70% and 61% and at 4 years are 52% and 47% respectively. Cumulative incidences (CI) of non-relapse mortality (NRM) and relapse at 1 yr are 17% and 21% and at 4 yrs are 24% and 29% (Fig.1). CI of acute GVHD grade 2-4 and 3-4 at 6 months were 28% and 10%. CI of moderate to severe, and severe chronic GVHD at 4 years were 30% and 12%. On multivariate analysis, receipt of any part of the conditioning regimen as inpatient was a significant negative factor for survival (HR 1.99, p Figure 1. Figure 1. Disclosures No relevant conflicts of interest to declare.

Introduction: Overall survival after allogeneic hematopoietic cell transplantation (HCT) is dependent on multiple patient, transplant and donor related factors. The national marrow donor program publishes survival outcomes from transplant centers focusing on the first year after allogeneic HCT. The first 12 months post allogeneic HCT carry a high risk of morbidity and mortality as well as a high risk of disease relapse. Many centers use the publically available one year data to advise patients on transplant risks and overall survival. The survival outcomes and the factors that affect these outcomes among allogeneic recipients who are alive and disease free at one year after HCT are not reported. The availability of such information will be of importance to council patients during their first anniversary visit and to identify the subgroup of survivals carrying a higher risk for later morbidity and mortality. Methods: We analyzed the outcomes of 667 consecutive adult patients at our center who received a first allogeneic transplant between 2005 and 2015. Patients were excluded from this analysis if they had less than one year of follow up (n=54), if died or had relapse of their disease (n=224) prior to the first year post-transplant. Patient characteristics and outcome parameters were extracted from our institutional database where they had been prospectively entered. Kaplan-Meier estimates of overall survival (OS) and disease-free survival (DFS) were calculated and the cumulative incidence method with competing risks was used to calculate rates of non-relapse mortality (NRM) and relapse. Cumulative incidences of acute and chronic GVHD were estimated with death being treated as the competing risk. Cox proportional hazards models, were developed using OS and relapse as endpoints and other parameters as covariates. All survival estimates were reported beyond the 1 year timeframe. GVHD was prospectively documented using established criteria including NIH consensus criteria for chronic GVHD and rates calculated using the cumulative incidence method. All patients were transplanted in the outpatient setting with hospital admissions for complications that could not be handled outpatient. Results: A total of 389 patients were included in the final analysis with a median age of 51 (19-75) years. Patients' characteristics were as follows: male (55%), race (white 77%, black 19%), disease ( AML 34%, ALL 15%, MDS/MPD 23%, NHL 24%), donor type ( MRD 37%, MUD 39%, haplo 24%), conditioning intensity (RIC 74%, myeloablative 53%), cell source ( bone marrow 19%), HCT comorbidity index >=3 (35%) and disease risk index DRI (high/very high 26%, intermediate 24%). The survival estimates at one and three years beyond the first year after transplant were Overall survival 91% and 82%, disease free survival 86% and 78%, transplant related mortality 7% and 12% and relapse of 7% and 10%. After adjusting for age, sex, race, diagnosis, cell source, CMV serostatus, disease risk index, transplant conditioning regimen, donor type, acute and chronic GVHD before 1 year and other significant factors, the cox model on mortality showed that male gender (HR 1.87, p=0.02), need of immunosuppression at 1 year (HR 2.17, p=0.006), and year of transplant (HR 0.62, p=0.026 for patients transplanted in 2013-2015 versus 2005-2009) were associated with higher mortality rate (fig 1). Cox model on relapse showed that male gender (HR 2.09, p=0.036), high/very high DRI (HR 26.40, p=0.002) to be associated with higher relapse whereas developing acute 2-4 GVHD (HR 0.32, p=0.011) or chronic GVHD (HR 0.33, p=0.001) in the first year after HCT was associated with lower relapse rates. Conclusion: patients who are alive and without relapse at one year post allogeneic HCT have an excellent long term survival and very low chance of disease relapse. A subset of patients with high/very high DRI remain at significant risk of later relapse and should be followed more closely with long term strategies to prevent delayed relapses. Figure 1 Kaplan-Meier Overall Survival Graphs by Gender, DRI and Year of Transplant Figure 1. Kaplan-Meier Overall Survival Graphs by Gender, DRI and Year of Transplant Disclosures No relevant conflicts of interest to declare.

Introduction: Outcomes for non-transplant therapy in older adults (age> 60 years) with AML or high-grade MDS have historically been poor. Allogeneic hematopoietic cell transplantation (allo-HCT) may improve these outcomes. However, many older patients will lack suitably HLA-matched sibling donors (MRD). Furthermore, many patients from ethnic minorities will lack an optimally matched unrelated donors (MUD). Additionally, the greater incidence and severity of chronic GVHD typically seen following MUD transplants may be particularly difficult to tolerate in older patients. T-replete haploidentical donor transplants (HAPLO) using post-transplant cyclophosphamide to mitigate alloreactivity may provide a suitable donor option for some older patients. However, no detailed comparison of outcomes after HAPLO to MRD and MUD donors in elderly patients with AML and high-grade MDS have been reported in the modern era.. Methods: We analyzed outcomes of patients aged > 60 years with AML or high-grade MDS who received an allo-HCT at our center between 2005 and 2015. Ex-vivo T-cell depleted transplants and cord blood transplants were excluded. Supportive care measures were identical between the three donor groups. Patient characteristics and outcome parameters were extracted from our institutional database where they had been prospectively entered. Kaplan-Meier estimates of overall survival (OS) and disease-free survival (DFS) were calculated and the cumulative incidence method with competing risks was used to calculate rates of non-relapse mortality (NRM) and relapse. Cumulative incidences of acute and chronic GVHD were estimated with death being treated as the competing risk. Cox proportional hazards models, stratified on the three transplant donor groups, were developed using OS, DFS, NRM and relapse as endpoints and other parameters as covariates. GVHD was prospectively documented by a single dedicated nurse using established criteria including NIH consensus criteria for chronic GVHD and rates calculated using the cumulative incidence method. Results: Patient characteristics (n=127, 33 HAPLO, 37 MRD, 57 MUD) were as follows: median age 64 (60-77); male 57%; regimen- myeloablative (24%) non-myeloablative (76%); graft- PBSC (80%) BM (20%); Diagnoses- AML 59%, MDS 41%; DRI- low (2%), intermediate (58%), high (39%), very high (1%); Sorror HCT-comorbidity index 0-2 (46%), >3 (54%); Median HLA mismatches were 5/10 (range 2/10 to 5/10) for HAPLO patients. Estimated rates of OS, DFS, NRM and relapse for the entire group at 2 years were 60%, 49%, 18%, and 33%. When compared to MRD and MUD, HAPLO patients had similar characteristics but were less likely to have myeloablative conditioning (6% vs. 32% and 30% respectively for MRD and MUD, p=0.016) and were more likely to have a BM graft (52% vs. 0% and 21%, p Conclusions: The results show that in the current era, using predominantly non-myeloablative conditioning regimens, 2 year OS and DFS rates of 60% and 49% with a NRM 60 years who undergo allo-HCT for AML and high-grade MDS. Outcomes of patients transplanted from HAPLO donors are comparable to those from matched donors although the rate of clinically significant chronic GVHD appears significantly less following HAPLO transplants, which may translate to an improved quality of life. Figure 1 Figure 1. Figure 2 Figure 2. Table 1 Multivariate Analysis on Overall Survival, Disease Free Survival, Transplant Related Mortality and Relapse Table 1. Multivariate Analysis on Overall Survival, Disease Free Survival, Transplant Related Mortality and Relapse Disclosures No relevant conflicts of interest to declare.

Introduction GVHD-free, relapse-free survival (GRFS) has been previously developed as a novel composite endpoint designed as a measure of transplant effectiveness, which attempts to take into account the morbidity associated with GVHD (Holtan et al. Blood 2015). The conventional definition of GRFS however considers grade 3-4 acute GVHD and immunosuppression-requiring chronic GVHD (cGVHD) as static endpoints, whereas in reality these outcomes are often reversible. Patients with short-lived GVHD are considered treatment failures, which may not represent an accurate measure of transplant success. Therefore, we have developed a statistical method that provides an estimate of the probability, at any time post-transplant, of being alive, in remission, and without clinically significant cGVHD, defined as moderate-severe by the NIH consensus criteria. Methods In this new composite endpoint, which we call current GRFS (CGRFS), death and relapse are treated as terminal events, while cGVHD is considered a dynamic event, which can "resolve" once manifestations are quiescent and systemic immunosuppression discontinued. Grade 3-4 acute GVHD was intentionally not included in this endpoint, as this event almost universally will either resolve with time or convert to either death or cGVHD, which are both captured as part of CGRFS. Statistically, the CGRFS was defined as the sum of the survival without evidence of relapse and moderate-severe cGVHD and the probability that one recovered from moderate-severe cGVHD. The probability that one recovered from moderate-severe cGVHD was calculated by looking at the differences of relevant Kaplan-Meier estimates. Comparison of CGRFS between two independent samples was implemented by the simulation-based supremum test. Results We evaluated 437 consecutive patients receiving an allogeneic hematopoietic stem cell transplant at a single institution from a matched related (MRD, n=125), matched unrelated (MUD, n=165), or haploidentical (HID, n=132) donor between January 2010 and July 2015. Transplant recipients had a median age of 54 years (range 18-77), DRI high/very high in 30%, and HCT-CI ³3 in 46%. Myeloablative conditioning was used in 50% and PBSC was the stem cell source in 78%. GVHD was prospectively documented by a dedicated practitioner on an ongoing basis. With a median follow-up time of 36 months, estimated 3-yr overall and disease-free survival was 61% and 54%, respectively. Conventionally defined GRFS at 1, 2, 3 and 4 years was 33%, 26%, 23%, and 22% respectively. In contrast, when moderate-severe cGVHD was treated as a dynamic event, corresponding CGRFS was 45%, 46%, 47% and 49%, respectively (Figure 1). The corresponding gain in CGRFS survival, due to the treatment of cGVHD as a dynamic event, was 12%, 20%, 24% and 27% respectively (Figure 2). Patients living with active mod-severe cGVHD decreased over time, quantitated at 23%, 14%, 7% and 4% respectively at 1, 2, 3 and 4 years post-transplant (Figure 3). CGRFS was significantly correlated with DRI (low/intermediate vs. high/very high, p Conclusion Whereas only a third of patients achieve "transplant success" by conventional 1-yr GRFS, nearly half of patients by CGRFS are considered cured without the morbidity of ongoing GVHD. We propose that CGRFS may represent are more accurate estimate of transplant effectiveness. Disclosures No relevant conflicts of interest to declare.

Donor Type and Disease Risk Predict the Success of Allogeneic Hematopoietic Cell Transplantation (HCT): A single Center Analysis of 613 Adult HCT Recipients Using a Modified Composite Endpoint Introduction The success of allogeneic HCT is based on long term survival, free of relapse or morbidity as commonly encountered when patients develop graft versus host disease (GVHD). The Bone marrow transplant clinical trials network (BMTCTN) recently incorporated a composite endpoint to determine success rate in ongoing clinical trials. The new composite endpoint of GVHD free, relapse free survival (GRFS) includes the factors of acute GVHD grade 3-4, relapse, death and chronic GVHD requiring systemic immunosuppression. As the decision to start patients on immunosuppression for chronic GVHD can be subjective and physician dependent, we elected to assess the success of allogeneic HCT using a more objective endpoint m-GRFS where the clinically significant negative events are acute GVHD grade 3-4, moderate-severe chronic GVHD, disease relapse and Death at 1 and 2-year post HCT. Methods Six hundreds and thirteen patients who underwent a first allogeneic HCT after a HLA-identical sibling (MRD, n=212), 10/10 matched unrelated donor (MUD, n=251) or T-replete haploidentical donor with post-transplant cyclophosphamide (HIDT, n=150) were included in this analysis. Patient, Disease and Transplant related variables were prospectively documented and obtained from our institutional database. The Kruksall-Wallis test was used to compare continuous variables and the Chi-squared test for categorical variables. OS, DFS and m-GRFS were estimated by the Kaplan-Meier (K-M) method. Log-log transformed confidence intervals for OS, DFS and GRFS were calculated. Comparison of m-GRFS between demographic subgroups and between clinical subgroups were evaluated using the log-rank test for the entire study period and using the Wald test for a select time point. Competing risks analysis was performed to disentangle the components of GRFS. Grade III/IV acute GVHD, mod-severe chronic GVHD, relapse and death were considered as competing risks and cumulative incidences of these endpoints were calculated. Patients were considered to have met the endpoint once any of the components occurred. Cox regression analysis was conducted to examine the impact of donor, demographic and clinical factors on the primary endpoint of modified GRFS. The proportional hazards assumption was checked by temporarily including and testing time-dependent variables and the variables in the final model passed the proportionality test. The adjusted GRFS for one characteristic was calculated as the average survival of the whole sample, assuming that everyone in the sample had this characteristic. Results The median follow-up was 50.2 months. Patients characteristics were as follows: median age 53 years (18-77), male 56%, reduced intensity/non-ablative 49%, AML 37%, ALL 13%, MDS/MPD 24%, bone marrow graft 19%, HCT-comorbidity index >=3 in 39%, and high/very high DRI 34%. The unadjusted Kaplan-Meier estimates for 1- and 2-year m-GRFS were 36% (95%CI 32%-40%) and 28% (95%CI 25%-32%). The 2-year m-GRFS for MRD recipients was 30% (24-36%), MUD 24% (19-30%) and HIDT 33% (26-41%). The most common event at 2 years post HCT was chronic GVHD (39%) followed by relapse (31%), acute GVHD 3-4(20%) and death (10%). After adjusting for age, gender, diagnosis, conditioning intensity, donor type, cell source, HCT-CI, DRI , donor-recipient gender mismatch and year of transplant, the multivariate cox model on m-GRFS showed donor type, DRI risk , donor recipient sex mismatch and year of transplant to be significant predictors of m-GRFS (table 1). Patients who received a MUD had worse GRFS compared to MRD (HR 1.39, p=0.003) whereas HIDT had similar GRFS to MRD (HR 1.10, p=0.43). HIDT had better GRFS than MUD (HR 0.79, p=0.046). The adjusted 1- and 2- year m-GRFS showed donor type (MUD vs MRD), DRI, donor-recipient sex mismatch and transplant year to be associated with worse GRFS (table 2). Conclusions m-GRFS is a useful measure of transplant success. It appears to be significantly impacted by several modifiable factors including donor type, donor-recipient sex match and also by DRI. Adjusting donor choice and early referral of patients for transplant evaluation to improve DRI can potentially overcome the negative impact of these factors. Disclosures No relevant conflicts of interest to declare.

The incidence of herpes zoster (HZ) in patients with non-Hodgkin lymphoma (NHL) receiving bortezomib-based therapy has not been well studied. We reviewed data from two phase II trials in which bortezomib was administered to 236 patients, median age 65 years, with relapsed/refractory mantle cell or indolent NHL. HZ occurred in 24 patients (10.2%) overall, with a comparable incidence in NHL histologic subgroups. Median time to HZ was 39 (range, 11–206) days. In total, 71% of patients who developed HZ were aged ≥ 65 years, compared to 48% without HZ (p = 0.03). Patients with HZ were more likely to have had received ≥ 2 lines of therapy (63% vs. 47%, p = 0.16). Six (25%) of the patients who developed HZ had received purine analogs, compared with 34 (16%) patients without HZ (p = 0.27). As the occurrence of HZ may complicate the course of indolent or mantle cell NHL in patients receiving bortezomib-based therapies, these patients, especially the elderly, should be strongly considered for antiviral prop...

s / Biol Blood Marrow Transplant 19 (2013) S279eS312 S308 cycles) and one patient received decitabine 20mg/m2 intravenously for 5 days for 3 cycles. Median initial Azacitidine dose of 50 mg/m2 (range, 25-75 mg/m2) were given at a median of 40 days (range, 38-101 days) post HSCT engraftment. Azacitidine doses were increased based on counts to a maximum dose of 75mg/m2. With a median follow-up of 24months (range, 1.7-49 months) 6 patients are alive in complete remission. Twenty-four month progression free survival is 51% with overall survival of 76%. Conclusion: Given the dismal results of progression free survival and overall survival following allogeneic HSCT in high risk AML or non responsive MDS, hypomethylating agents given post transplantation provide a valuable approach to prolonging remission.

Stem cell mobilization in heavily pretreated multiple myeloma patients with prior high dose melphalan and auto-SCT

Disease Risk Index is the Major Predictor of Outcome Following Myeloablative Haploidentical Hematopoietic Stem Cell Transplantation (haplo-HSCT) and Post-Transplant Cyclophosphamide (PT/Cy) Although non-myeloablative (NMA) haplo-HSCT utilizing PT/Cy results in low rates of GVHD, infection, and non-relapse mortality (NRM), relapse remains the predominant cause of treatment failure, occurring in up to 50% of patients. To reduce the risk of relapse often associated with the use of NMA preparative regimens, we have developed a myeloablative haplo-HSCT utilizing PT/Cy. Sixty-four patients have been transplanted following either Busulfan-based (n=20) or TBI-based (n=44) myeloablative conditioning, T-cell replete PBSC infusion, PT/Cy, and tacrolimus/mycophenolate mofetil. Median age was 43 (range 21-60). Patient characteristics included a high/very high disease risk by the Dana-Farber/CIBMTR disease risk index (DRI) in 32 patients (50%), KPS Figure 1. Figure 1. Disclosures No relevant conflicts of interest to declare.