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•OS of patients aged ≥60 years with NPM1-mutant AML was similar with IC vs HMA/VEN after adjustment for clinicopathologic characteristics.•Patients with normal cytogenetics and without a concurrent FLT3internal tandem duplication mutation might benefit from treatment with IC over HMA/VEN.

Molecularly defined secondary acute myeloid leukemia is associated with a prior myeloid neoplasm and confers a worse prognosis. We compared outcomes of molecularly defined secondary AML patients (n= 395) treated with daunorubicin and cytarabine (7 + 3, n= 167), liposomal daunorubicin and cytarabine (CPX-351, n= 66) or hypomethylating agents (HMA) + venetoclax (VEN) (n= 162). Median overall survival (OS) was comparable between treatment groups among patients aged >60 years. In a multivariable model HMA + VEN vs. 7 + 3 was associated with better OS (hazard ratio [HR] 0.64 [95% confidence interval (CI) 0.42–0.98, p= 0.041]), whereas CPX-351 vs. 7 + 3 was not (HR 0.79 [CI 95% 0.50–1.25, p= 0.31]). Allogeneic hematopoietic stem cell transplantation, BCORand IDHmutations were associated with improved OS; older age, prior myeloid disease, NRAS/KRASmutations, EZH2mutation, and monosomal karyotype were associated with worse OS. When analyzed in each treatment separately, the IDHco-mutations benefit was seen with 7 + 3 and the detrimental effect of NRAS/KRASco-mutations with HMA + VEN and CPX-351. In pairwise comparisons adjusted for age, HMA + VEN was associated with improved OS vs. 7 + 3 in patients with SF3B1mutation and improved OS vs. CPX-351 in those with RNA splicing factor mutations. In molecularly defined secondary AML treatment with HMA + VEN might be preferred but could further be guided by co-mutations.

We conducted a multi-center study to analyze factors predicting survival among patients with TP53-mutated (m) AML receiving allogeneic hematopoietic stem cell transplant (allo-HSCT) in the recent era. Out of 370 TP53m AML patients, 68 (18%) patients were bridged to allo-HSCT. The median age of the patients was 63 years (range, 33–75), 82% of patients had complex cytogenetics and 66% of patients had multi-hit TP53m. Forty three percent received myeloablative conditioning and 57% received reduced intensity conditioning. The incidence of acute graft versus host disease (GVHD) was 37% and chronic GVHD was 44%. The median event-free survival (EFS) from the time of allo-HSCT was 12.4 months (95% CI: 6.24–18.55) and median overall survival (OS) was 24.5 months (95% CI: 21.80–27.25). In multivariate analysis utilizing variables that showed significance in univariate analysis, complete remission at day 100 post allo-HSCT retained significance for EFS (HR: 0.24, 95% CI: 0.10–0.57, p= 0.001) and OS (HR: 0.22, 95% CI: 0.10–0.50, p≤ 0.001). Similarly, occurrence of chronic GVHD retained significance for EFS (HR: 0.21, 95% CI: 0.09–0.46, p≤ 0.001) and OS (HR: 0.34, 95% CI: 0.15–0.75, p= 0.007). Our report suggests that allo-HSCT offers the best opportunity to improve long-term outcome among patients with TP53m AML.

TP53-mutated acute myeloid leukaemia is associated with poor outcomes. Eprenetapopt (APR-246) is a first-in-class, small-molecule p53 reactivator. We aimed to evaluate the combination of eprenetapopt and venetoclax with or without azacitidine in patients with TP53-mutated acute myeloid leukaemia.

Plasmacytoid dendritic cells (pDCs) are the principal natural type I interferon–producing dendritic cells. Neoplastic expansion of pDCs and pDC precursors leads to blastic plasmacytoid dendritic cell neoplasm (BPDCN), and clonal expansion of mature pDCs has been described in chronic myelomonocytic leukemia. The role of pDC expansion in acute myeloid leukemia (AML) is poorly studied. Here, we characterize patients with AML with pDC expansion (pDC-AML), which we observe in ∼5% of AML cases. pDC-AMLs often possess cross-lineage antigen expression and have adverse risk stratification with poor outcome. RUNX1 mutations are the most common somatic alterations in pDC-AML (>70%) and are much more common than in AML without pDC expansion and BPDCN. We demonstrate that pDCs are clonally related to, as well as originate from, leukemic blasts in pDC-AML. We further demonstrate that leukemic blasts from RUNX1-mutated AML upregulate a pDC transcriptional program, poising the cells toward pDC differentiation and expansion. Finally, tagraxofusp, a targeted therapy directed to CD123, reduces leukemic burden and eliminates pDCs in a patient-derived xenograft model. In conclusion, pDC-AML is characterized by a high frequency of RUNX1 mutations and increased expression of a pDC transcriptional program. CD123 targeting represents a potential treatment approach for pDC-AML.

Plasmacytoid dendritic cells (pDCs) are the principal natural type I interferon–producing dendritic cells. Neoplastic expansion of pDCs and pDC precursors leads to blastic plasmacytoid dendritic cell neoplasm (BPDCN), and clonal expansion of mature pDCs has been described in chronic myelomonocytic leukemia. The role of pDC expansion in acute myeloid leukemia (AML) is poorly studied. Here, we characterize patients with AML with pDC expansion (pDC-AML), which we observe in ∼5% of AML cases. pDC-AMLs often possess cross-lineage antigen expression and have adverse risk stratification with poor outcome. RUNX1mutations are the most common somatic alterations in pDC-AML (>70%) and are much more common than in AML without pDC expansion and BPDCN. We demonstrate that pDCs are clonally related to, as well as originate from, leukemic blasts in pDC-AML. We further demonstrate that leukemic blasts from RUNX1-mutated AML upregulate a pDC transcriptional program, poising the cells toward pDC differentiation and expansion. Finally, tagraxofusp, a targeted therapy directed to CD123, reduces leukemic burden and eliminates pDCs in a patient-derived xenograft model. In conclusion, pDC-AML is characterized by a high frequency of RUNX1mutations and increased expression of a pDC transcriptional program. CD123 targeting represents a potential treatment approach for pDC-AML.

Azacitidine + venetoclax, decitabine + venetoclax, and low-dose cytarabine + venetoclax are now standard treatments for newly diagnosed older or unfit patients with acute myeloid leukemia (AML). Although these combinations are also commonly used in relapsed or refractory AML (RR-AML), clinical and molecular predictors of response and survival in RR-AML are incompletely understood. We retrospectively analyzed clinical and molecular characteristics and outcomes for 86 patients with RR-AML who were treated with venetoclax combinations. The complete remission (CR) or CR with incomplete hematologic recovery (CRi) rate was 24%, and the overall response rate was 31% with the inclusion of a morphologic leukemia-free state. Azacitidine + venetoclax resulted in higher response rates compared with low-dose cytarabine + venetoclax (49% vs 15%; P = .008). Median overall survival (OS) was 6.1 months, but it was significantly longer with azacitidine + venetoclax compared with low-dose cytarabine + venetoclax (25 vs 3.9 months; P = .003). This survival advantage of azacitidine + venetoclax over low-dose cytarabine + venetoclax persisted when patients were censored for subsequent allogeneic stem cell transplantation (8.1 vs 3.9 months; P = .035). Mutations in NPM1 were associated with higher response rates, whereas adverse cytogenetics and mutations in TP53, KRAS/NRAS, and SF3B1 were associated with worse OS. Relapse was driven by diverse mechanisms, including acquisition of novel mutations and an increase in cytogenetic complexity. Venetoclax combination therapy is effective in many patients with RR-AML, and pretreatment molecular characteristics may predict outcomes. Trials that evaluate novel agents in combination with venetoclax therapy in patients with RR-AML that have adverse risk genomic features are warranted.

Azacitidine + venetoclax, decitabine + venetoclax, and low-dose cytarabine + venetoclax are now standard treatments for newly diagnosed older or unfit patients with acute myeloid leukemia (AML). Although these combinations are also commonly used in relapsed or refractory AML (RR-AML), clinical and molecular predictors of response and survival in RR-AML are incompletely understood. We retrospectively analyzed clinical and molecular characteristics and outcomes for 86 patients with RR-AML who were treated with venetoclax combinations. The complete remission (CR) or CR with incomplete hematologic recovery (CRi) rate was 24%, and the overall response rate was 31% with the inclusion of a morphologic leukemia-free state. Azacitidine + venetoclax resulted in higher response rates compared with low-dose cytarabine + venetoclax (49% vs 15%; P= .008). Median overall survival (OS) was 6.1 months, but it was significantly longer with azacitidine + venetoclax compared with low-dose cytarabine + venetoclax (25 vs 3.9 months; P= .003). This survival advantage of azacitidine + venetoclax over low-dose cytarabine + venetoclax persisted when patients were censored for subsequent allogeneic stem cell transplantation (8.1 vs 3.9 months; P= .035). Mutations in NPM1were associated with higher response rates, whereas adverse cytogenetics and mutations in TP53, KRAS/NRAS, and SF3B1were associated with worse OS. Relapse was driven by diverse mechanisms, including acquisition of novel mutations and an increase in cytogenetic complexity. Venetoclax combination therapy is effective in many patients with RR-AML, and pretreatment molecular characteristics may predict outcomes. Trials that evaluate novel agents in combination with venetoclax therapy in patients with RR-AML that have adverse risk genomic features are warranted.

Coronavirus disease 2019 (COVID-19) is an illness resulting from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that emerged in late 2019. Patients with cancer, and especially those with hematologic malignancies, may be at especially high risk of adverse outcomes, including mortality resulting from COVID-19 infection. The ASH Research Collaborative COVID-19 Registry for Hematology was developed to study features and outcomes of COVID-19 infection in patients with underlying blood disorders, such as hematologic malignancies. At the time of this report, data from 250 patients with blood cancers from 74 sites around the world had been entered into the registry. The most commonly represented malignancies were acute leukemia (33%), non-Hodgkin lymphoma (27%), and myeloma or amyloidosis (16%). Patients presented with a myriad of symptoms, most frequently fever (73%), cough (67%), dyspnea (50%), and fatigue (40%). Use of COVID-19–directed therapies, such as hydroxychloroquine (n = 76) or azithromycin (n = 59), was common. Overall mortality was 28%. Patients with a physician-estimated prognosis from the underlying hematologic malignancy of <12 months at the time of COVID-19 diagnosis and those with relapsed/refractory disease experienced a higher proportion of moderate/severe COVID-19 disease and death. In some instances, death occurred after a decision was made to forgo intensive care unit admission in favor of a palliative approach. Taken together, these data support the emerging consensus that patients with hematologic malignancies experience significant morbidity and mortality resulting from COVID-19 infection. Batch submissions from sites with high incidence of COVID-19 infection are planned to support future analyses.

Coronavirus disease 2019 (COVID-19) is an illness resulting from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that emerged in late 2019. Patients with cancer, and especially those with hematologic malignancies, may be at especially high risk of adverse outcomes, including mortality resulting from COVID-19 infection. The ASH Research Collaborative COVID-19 Registry for Hematology was developed to study features and outcomes of COVID-19 infection in patients with underlying blood disorders, such as hematologic malignancies. At the time of this report, data from 250 patients with blood cancers from 74 sites around the world had been entered into the registry. The most commonly represented malignancies were acute leukemia (33%), non-Hodgkin lymphoma (27%), and myeloma or amyloidosis (16%). Patients presented with a myriad of symptoms, most frequently fever (73%), cough (67%), dyspnea (50%), and fatigue (40%). Use of COVID-19–directed therapies, such as hydroxychloroquine (n = 76) or azithromycin (n = 59), was common. Overall mortality was 28%. Patients with a physician-estimated prognosis from the underlying hematologic malignancy of <12 months at the time of COVID-19 diagnosis and those with relapsed/refractory disease experienced a higher proportion of moderate/severe COVID-19 disease and death. In some instances, death occurred after a decision was made to forgo intensive care unit admission in favor of a palliative approach. Taken together, these data support the emerging consensus that patients with hematologic malignancies experience significant morbidity and mortality resulting from COVID-19 infection. Batch submissions from sites with high incidence of COVID-19 infection are planned to support future analyses.

Myeloid malignancies, including acute myeloid leukaemia (AML), arise from the expansion of haematopoietic stem and progenitor cells that acquire somatic mutations. Bulk molecular profiling has suggested that mutations are acquired in a stepwise fashion: mutant genes with high variant allele frequencies appear early in leukaemogenesis, and mutations with lower variant allele frequencies are thought to be acquired later1–3. Although bulk sequencing can provide information about leukaemia biology and prognosis, it cannot distinguish which mutations occur in the same clone(s), accurately measure clonal complexity, or definitively elucidate the order of mutations. To delineate the clonal framework of myeloid malignancies, we performed single-cell mutational profiling on 146 samples from 123 patients. Here we show that AML is dominated by a small number of clones, which frequently harbour co-occurring mutations in epigenetic regulators. Conversely, mutations in signalling genes often occur more than once in distinct subclones, consistent with increasing clonal diversity. We mapped clonal trajectories for each sample and uncovered combinations of mutations that synergized to promote clonal expansion and dominance. Finally, we combined protein expression with mutational analysis to map somatic genotype and clonal architecture with immunophenotype. Our findings provide insights into the pathogenesis of myeloid transformation and how clonal complexity evolves with disease progression.

The ongoing COVID-19 pandemic caused by severe acute respiratory syndrome coronavirus 2 is a global public health crisis. Multiple observations indicate poorer post-infection outcomes for patients with cancer than for the general population. Herein, we highlight the challenges in caring for patients with acute leukaemias and myeloid neoplasms amid the COVID-19 pandemic. We summarise key changes related to service allocation, clinical and supportive care, clinical trial participation, and ethical considerations regarding the use of lifesaving measures for these patients. We recognise that these recommendations might be more applicable to high-income countries and might not be generalisable because of regional differences in health-care infrastructure, individual circumstances, and a complex and highly fluid health-care environment. Despite these limitations, we aim to provide a general framework for the care of patients with acute leukaemias and myeloid neoplasms during the COVID-19 pandemic on the basis of recommendations from international experts.

•Treatment-naive and relapsed/refractory MDS patients receiving venetoclax and HMAs have an ORR of 59% with 63% of responders proceeding to transplant.•Allogeneic stem cell transplantation after treatment with venetoclax in combination with HMA is associated with prolonged survival.

Introduction:

INTRODUCTION:Luxeptinib (CG-806; LUX) is an orally active noncovalent kinase inhibitor of Bruton's tyrosine kinase (BTK), wild type and mutant forms of Fms-like tyrosine kinase 3 (FLT3) (including the internal tandem duplicates (ITD), tyrosine kinase domain (TKD), and F691L mutant forms), and growth receptors like KIT, CSF1R, PDGFRα, and TRKs. In prior studies, LUX has been shown to suppress aberrant proliferative signaling in B cell malignancies and acute myeloid leukemia (AML) via regulation of BTK, LYN, SYK, AKT, ERK, and MAPK. LUX is cytotoxic to primary AML cells insensitive to other FLT3 inhibitors and to malignant B-cells insensitive to ibrutinib, at pM and nM concentrations, respectively.

Introduction: Venetoclax (V) / Obinutuzumab (O) is an effective one-year fixed duration therapy for patients (pts) requiring first-line CLL treatment (tx). In CLL14, tumor lysis syndrome (TLS) risk assessment (including lymph node measurements by imaging and ALC) was required once prior to tx initiation, and O's impact on TLS risk prior to introduction of V was not a pre-planned study endpoint. Therefore, TLS prophylaxis (ppx) and tx setting for V dose escalation did not account for the possibility that O may decrease TLS risk prior to V escalation. Based on this approach, 22% of pts in the CLL14 study were high risk for TLS, thus requiring hospitalization for intensive laboratory monitoring during V dose escalation. (Fischer, NEJM 2019) We hypothesized that cycle (C) 1 of O would significantly decrease TLS risk prior to V escalation and that all pts, regardless of TLS risk category, could safely undergo a standard 5-week V dose escalation in the outpatient setting.

Background and Significance:

Background

Introduction: The BCL-2 inhibitor VEN is approved in combination with hypomethylating agents or low-dose cytarabine for adults with ND AML. The ARC Initiative is a multicenter chart review study of adult pts with AML. This abstract presents real-world clinical outcomes and hospitalizations among ND AML VEN treated pts ineligible for intensive chemotherapy (IC) and their matched controls.

Introduction:

Introduction:25-30% of adult patients with AML have mutations in the isocitrate dehydrogenase (IDH) genes, IDH1or IDH2. Hypomethylating agents (HMA) and venetoclax (Ven) is a widely used combination in induction-ineligible patients with IDHmutations. A subset analysis of VIALE-A data showed composite complete remission or complete remission with incomplete hematologic recovery (CR/CRi) rate of 79% and median overall survival (mOS) of 24.5 months with frontline azacitidine and Ven. IDH1-mutant and IDH2-mutant patients had CR/CRi rates of 66.7% and 86.0%, respectively. IDH1-mutant patients had mOS of 15.2 months and IDH2-mutant patients did not reach mOS. We report a single-center retrospective analysis of HMA/Ven in patients with IDHmutations.

Introduction

Background:TP53gene mutations lead to inactivation of the protein p53, causing genome instability, oncogenesis, and treatment resistance conferring an unfavorable prognosis. TP53Y220C missense mutations in exon 6 (p.659A>G) are described as a frequent ‘hot spot’ mutation in solid tumors. A novel Y220C-targeted small molecule (PC14586) has shown preliminary efficacy and safety in patients with solid tumors (Dumbrava, E., ASCO 2022). No data has been reported about TP53Y220C in hematologic malignancies to date. We set out to evaluate the clinicopathologic characteristics of TP53Y220C in hematologic malignancies and particularly, myeloid neoplasms.

Introduction:Venetoclax (VEN), a novel BCL-2 inhibitor, received accelerated FDA approval for the treatment of newly diagnosed (ND) acute myeloid leukemia (AML) in adults aged 75 years or older, or who have comorbidities precluding use of intensive chemotherapy, in combination with hypomethylating agents (HMAs: azacitidine [AZA] or decitabine [DEC]), or low-dose cytarabine (LDAC). As Phase III trials have demonstrated relative efficacy of VEN combinations, this real-world initiative provides insight into the characteristics and outcomes of ND AML patients (pts) treated with VEN combinations vs non-VEN-based regimens in clinical practice.

Pollyea: Syndax: Consultancy; Syros: Consultancy; Novartis: Consultancy; Karyopharm: Consultancy; Janssen: Consultancy; 47: Consultancy, Research Funding; Genentech: Consultancy; Takeda: Consultancy; Celgene/BMS: Consultancy; Agios: Consultancy; Glycomimetics: Other; Amgen: Consultancy; Abbvie: Consultancy, Research Funding; Daiichi Sankyo: Consultancy; Pfizer: Consultancy. Talati:BMS: Honoraria; Jazz: Speakers Bureau; AbbVie: Honoraria; Pfizer: Honoraria; Astellas: Speakers Bureau. Lai:Abbvie: Consultancy; Jazz: Speakers Bureau; Astellas: Speakers Bureau; Macrogenics: Consultancy; Agios: Consultancy. Abedin:Helsinn Healthcare: Honoraria; Agios: Honoraria; Jazz Pharmaceuticals: Honoraria; Pfizer: Research Funding; Helsinn Healthcare: Research Funding; Actinium Pharmaceuticals: Research Funding. Zeidner:Sumitomo Dainippon Pharma Oncology, Inc.: Research Funding; Merck: Research Funding; Forty-Seven: Other: Travel Reimbursement, Research Funding; AROG: Research Funding; AsystBio Laboratories: Consultancy; Daiichi Sankyo: Honoraria; Takeda: Consultancy, Honoraria, Other: Travel Reimbursement, Research Funding; Pfizer: Honoraria; Genentech: Honoraria; Celgene: Consultancy, Honoraria, Research Funding; AbbVie: Honoraria, Other: Independent Review Committee; Agios: Honoraria. Xavier:Kite/Gilead: Honoraria, Membership on an entity's Board of Directors or advisory committees; AbbVie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; AstraZeneca: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees; Morphosys: Honoraria, Membership on an entity's Board of Directors or advisory committees; TG therapeutics: Honoraria, Membership on an entity's Board of Directors or advisory committees; Verastem: Honoraria, Membership on an entity's Board of Directors or advisory committees; Acrotec: Consultancy, Speakers Bureau; Biegene: Speakers Bureau; Genentech: Speakers Bureau; Seattle Genetics: Speakers Bureau; Celgene/BMS: Speakers Bureau; Epizyme: Speakers Bureau; Astellas: Speakers Bureau; Incyte: Speakers Bureau. Wolach:AbbVie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Fees for lectures and Consultancy, Research Funding; Pfizer: Consultancy, Honoraria; Janssen: Other: Fees for lectures and Consultancy; Amgen: Other: Fees for lectures and Consultancy; Astellas: Consultancy, Honoraria, Other: Fees for lectures and Consultancy; Novartis: Consultancy, Honoraria, Other: Fees for lectures and Consultancy. Moshe:Novartis: Membership on an entity's Board of Directors or advisory committees, Other: Lecturer; Astellas: Membership on an entity's Board of Directors or advisory committees, Other: lecturer; AbbVie: Membership on an entity's Board of Directors or advisory committees, Other: Fee for lec. Choi:AbbVie: Current Employment, Current equity holder in publicly-traded company. Bui:AbbVie: Current Employment, Current equity holder in publicly-traded company. Svensson:AbbVie: Current Employment, Current equity holder in publicly-traded company. Kye:AbbVie: Current Employment, Other: may hold stock or other options. Burne:Analysis Group, Inc., which has received consultancy fees from AbbVie: Current Employment. Guerin:Abbvie: Consultancy, Other; Sanofi Genzyme: Consultancy, Other: Annie Guerin is an employee of Analysis Group, Inc. which received consultancy fees from Sanofi Genzyme.; Novartis Pharmaceuticals Corporation: Consultancy, Other: Annie Guerin is an employee of Analysis Group, Inc. which received consultancy fees from Novartis.. Ma:Genentech, Inc.: Current Employment, Current equity holder in publicly-traded company. Montez:Genentech, Inc.: Current Employment; F. Hoffmann-La Roche: Current equity holder in publicly-traded company. Goldberg:Dava Oncology: Honoraria; Pfizer: Research Funding; Celularity: Research Funding; AROG: Research Funding; Aprea: Research Funding; ADC Therapeutics: Research Funding; Genentech: Consultancy, Membership on an entity's Board of Directors or advisory committees; Daiichi Sankyo: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Consultancy; AbbVie: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Aptose: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding.

Cai: Imago Biosciences, Inc.: Consultancy, Current equity holder in private company; DAVA Oncology: Honoraria. Geyer:Amgen: Research Funding. Glass:Gerson Lehman Group: Consultancy. Stein:Syros: Membership on an entity's Board of Directors or advisory committees; PTC Therapeutics: Membership on an entity's Board of Directors or advisory committees; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Biotheryx: Consultancy; Bayer: Research Funding; Genentech: Consultancy, Membership on an entity's Board of Directors or advisory committees; Syndax: Consultancy, Research Funding; Seattle Genetics: Consultancy; Abbvie: Consultancy; Amgen: Consultancy; Celgene Pharmaceuticals: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Agios Pharmaceuticals: Consultancy, Membership on an entity's Board of Directors or advisory committees; Astellas Pharmaceuticals: Consultancy, Membership on an entity's Board of Directors or advisory committees; Daiichi-Sankyo: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding. Levine:Gilead: Honoraria; Isoplexis: Current equity holder in private company, Membership on an entity's Board of Directors or advisory committees; Qiagen: Current equity holder in publicly-traded company, Membership on an entity's Board of Directors or advisory committees; Celgene: Consultancy, Honoraria, Research Funding; Janssen: Consultancy; Lilly: Consultancy, Honoraria; Imago: Current equity holder in private company, Membership on an entity's Board of Directors or advisory committees; C4 Therapeutics: Current equity holder in private company, Membership on an entity's Board of Directors or advisory committees; Astellas: Consultancy; Novartis: Consultancy; Prelude Therapeutics: Research Funding; Loxo: Current equity holder in private company, Membership on an entity's Board of Directors or advisory committees; Amgen: Honoraria; Morphosys: Consultancy; Roche: Consultancy, Honoraria, Research Funding. Gyurkocza:Actinium: Research Funding. Perales:Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees; Nektar Therapeutics: Honoraria, Membership on an entity's Board of Directors or advisory committees; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees; MolMed: Membership on an entity's Board of Directors or advisory committees; Abbvie: Honoraria, Membership on an entity's Board of Directors or advisory committees; Medigene: Membership on an entity's Board of Directors or advisory committees, Other; Servier: Membership on an entity's Board of Directors or advisory committees, Other; Omeros: Honoraria, Membership on an entity's Board of Directors or advisory committees; Merck: Consultancy, Honoraria; NexImmune: Membership on an entity's Board of Directors or advisory committees; Cidara Therapeutics: Other; Miltenyi Biotec: Research Funding; Kite/Gilead: Honoraria, Research Funding; Incyte Corporation: Honoraria, Research Funding; Bristol Myers Squibb: Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene: Honoraria; Bellicum: Honoraria, Membership on an entity's Board of Directors or advisory committees. Abdel-Wahab:H3 Biomedicine Inc.: Consultancy, Research Funding; Janssen: Consultancy; Envisagenics Inc.: Current equity holder in private company; Merck: Consultancy. Papaemmanuil:Kyowa Hakko Kirin: Consultancy, Honoraria; Isabl: Current equity holder in private company, Membership on an entity's Board of Directors or advisory committees; MSKCC: Patents & Royalties; Novartis: Consultancy, Honoraria; Illumina: Consultancy, Honoraria; Celgene: Consultancy, Honoraria, Research Funding; Prime Oncology: Consultancy, Honoraria. Giralt:KITE: Consultancy; NOVARTIS: Consultancy, Honoraria, Research Funding; OMEROS: Consultancy, Honoraria; AMGEN: Consultancy, Research Funding; TAKEDA: Research Funding; ACTINUUM: Consultancy, Research Funding; MILTENYI: Consultancy, Research Funding; CELGENE: Consultancy, Honoraria, Research Funding; JAZZ: Consultancy, Honoraria. Tallman:Glycomimetics: Research Funding; Rafael: Research Funding; Amgen: Research Funding; Bioline rx: Membership on an entity's Board of Directors or advisory committees; Daiichi-Sankyo: Membership on an entity's Board of Directors or advisory committees; KAHR: Membership on an entity's Board of Directors or advisory committees; UpToDate: Patents & Royalties; Rigel: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees; Roche: Membership on an entity's Board of Directors or advisory committees; Jazz Pharma: Membership on an entity's Board of Directors or advisory committees; Oncolyze: Membership on an entity's Board of Directors or advisory committees; Delta Fly Pharma: Membership on an entity's Board of Directors or advisory committees; BioSight: Membership on an entity's Board of Directors or advisory committees, Research Funding; ADC Therapeutics: Research Funding; Orsenix: Research Funding; Cellerant: Research Funding; Abbvie: Research Funding. Goldberg:AROG: Research Funding; Aprea: Research Funding; ADC Therapeutics: Research Funding; Genentech: Consultancy, Membership on an entity's Board of Directors or advisory committees; Daiichi Sankyo: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Consultancy; Aptose: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; AbbVie: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Dava Oncology: Honoraria; Pfizer: Research Funding; Celularity: Research Funding.

Background:Measurable residual disease (MRD) is a powerful prognostic factor in AML, including in prediction of outcomes post allogeneic stem cell transplant (alloSCT). However, genomic predictors of successful MRD eradication with chemotherapy prior to alloSCT are unclear.

•Ontogeny assignment from the database registry lacks sensitivity and specificity.•Ontogeny stratifies the outcome of AML with MR gene mutations.

Case studies have shown that when conventional concrete mixtures are used in congested drilled shafts, lack of adequate workability or flow between reinforcing bars may lead to trapped laitance or segregation between the inside and outside of the reinforcing cage. Due to its flow-ability and resistance to segregation, self-consolidating concrete (SCC) was evaluated as a viable material to overcome this problem. Several 1.8-m (6-ft) diameter drilled shafts were constructed using SCC as part of a field trial during the Lumber River Bridge Project, South Carolina. Identical shafts were constructed with SCC and a high slump gravel-aggregate concrete mixture typically used in coastal South Carolina. Both mixtures were observed to have excellent workability characteristics. Observations of the hardened concrete from exhumed drilled shafts indicate that generally good performance can be achieved in difficult construction conditions (congested cage, tremie placement, and lengthy placement times) if highly workable concrete is used. Some imperfections in the concrete were observed, even under these closely monitored conditions, and some degree of imperfection in this type of construction appears to be practically unavoidable. The imperfections observed in these field trials were detected by crosshole sonic logging, but they do not appear to have significant adverse consequences for foundation performance. On the basis of results of this project, it is concluded that SCC may be feasible for use in congested drilled shaft applications.

Wood: Pfizer: Research Funding; Teladoc/Best Doctors: Consultancy; ASH Research Collaborative: Honoraria. Neuberg:Celgene: Research Funding; Madrigak Pharmaceuticals: Current equity holder in publicly-traded company; Pharmacyclics: Research Funding. Tallman:Amgen: Research Funding; UpToDate: Patents & Royalties; Bioline rx: Membership on an entity's Board of Directors or advisory committees; Daiichi-Sankyo: Membership on an entity's Board of Directors or advisory committees; KAHR: Membership on an entity's Board of Directors or advisory committees; Rigel: Membership on an entity's Board of Directors or advisory committees; Delta Fly Pharma: Membership on an entity's Board of Directors or advisory committees; Oncolyze: Membership on an entity's Board of Directors or advisory committees; BioSight: Membership on an entity's Board of Directors or advisory committees, Research Funding; Cellerant: Research Funding; Orsenix: Research Funding; ADC Therapeutics: Research Funding; Roche: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees; Jazz Pharma: Membership on an entity's Board of Directors or advisory committees; Rafael: Research Funding; Glycomimetics: Research Funding; Abbvie: Research Funding. Sekeres:BMS: Consultancy; Takeda/Millenium: Consultancy; Pfizer: Consultancy. Sehn:Karyopharm: Consultancy, Honoraria; Gilead: Consultancy, Honoraria; Kite: Consultancy, Honoraria; Amgen: Consultancy, Honoraria; AbbVie: Consultancy, Honoraria; Apobiologix: Consultancy, Honoraria; AstraZeneca: Consultancy, Honoraria; Celgene: Consultancy, Honoraria; Acerta: Consultancy, Honoraria; TG therapeutics: Consultancy, Honoraria; Chugai: Consultancy, Honoraria; Servier: Consultancy, Honoraria; Takeda: Consultancy, Honoraria; Teva: Consultancy, Honoraria, Research Funding; Seattle Genetics: Consultancy, Honoraria; F. Hoffmann-La Roche Ltd: Consultancy, Honoraria, Research Funding; MorphoSys: Consultancy, Honoraria; Merck: Consultancy, Honoraria; Lundbeck: Consultancy, Honoraria; Genentech, Inc.: Consultancy, Honoraria, Research Funding; Janssen: Consultancy, Honoraria; Verastem Oncology: Consultancy, Honoraria. Anderson:Janssen: Membership on an entity's Board of Directors or advisory committees; Sanofi-Aventis: Membership on an entity's Board of Directors or advisory committees; Bristol Myers Squibb: Membership on an entity's Board of Directors or advisory committees; Oncopep and C4 Therapeutics.: Other: Scientific Founder of Oncopep and C4 Therapeutics.; Gilead: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees; Millenium-Takeda: Membership on an entity's Board of Directors or advisory committees. Goldberg:Dava Oncology: Honoraria; ADC Therapeutics: Research Funding; Genentech: Consultancy, Membership on an entity's Board of Directors or advisory committees; Daiichi Sankyo: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Consultancy; Aptose: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; AbbVie: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Pfizer: Research Funding; Celularity: Research Funding; AROG: Research Funding; Aprea: Research Funding. Pennell:Astrazeneca: Consultancy; BMS: Consultancy; Eli Lilly: Consultancy; Amgen: Consultancy; Genentech: Consultancy; Cota: Consultancy; Merck: Consultancy; Inivata: Consultancy; G1 Therapeutics: Consultancy. Niemeyer:Celgene: Consultancy; Novartis: Consultancy. Hicks:Gilead Sciences: Research Funding.

Background:Venetoclax combined with azacitidine (aza/ven), decitabine (dec/ven), and low-dose cytarabine (LDAC/ven) is commonly used off-label in relapsed/refractory (RR)-AML patients; however, predictors of response and survival are incompletely understood.