Foster, Matthew C

Abstract Enasidenib (ENA) is an inhibitor of isocitrate dehydrogenase 2 (IDH2) approved for the treatment of patients with IDH2-mutant relapsed/refractory acute myeloid leukemia (AML). In this phase 2/1b Beat AML substudy, we applied a risk-adapted approach to assess the efficacy of ENA monotherapy for patients aged ≥60 years with newly diagnosed IDH2-mutant AML in whom genomic profiling demonstrated that mutant IDH2 was in the dominant leukemic clone. Patients for whom ENA monotherapy did not induce a complete remission (CR) or CR with incomplete blood count recovery (CRi) enrolled in a phase 1b cohort with the addition of azacitidine. The phase 2 portion assessing the overall response to ENA alone demonstrated efficacy, with a composite complete response (cCR) rate (CR/CRi) of 46% in 60 evaluable patients. Seventeen patients subsequently transitioned to phase 1b combination therapy, with a cCR rate of 41% and 1 dose-limiting toxicity. Correlative studies highlight mechanisms of clonal elimination with differentiation therapy as well as therapeutic resistance. This study demonstrates both efficacy of ENA monotherapy in the upfront setting and feasibility and applicability of a risk-adapted approach to the upfront treatment of IDH2-mutant AML. This trial is registered at www.clinicaltrials.gov as #NCT03013998.

AbstractBackgroundPatients with acute myeloid leukemia (AML) who have tumor protein p53 (TP53) mutations or a complex karyotype have a poor prognosis, and hypomethylating agents are often used. The authors evaluated the efficacy of entospletinib, an oral inhibitor of spleen tyrosine kinase, combined with decitabine in this patient population.MethodsThis was a multicenter, open‐label, phase 2 substudy of the Beat AML Master Trial (ClinicalTrials.gov identifier NCT03013998) using a Simon two‐stage design. Eligible patients aged 60 years or older who had newly diagnosed AML with mutations in TP53 with or without a complex karyotype (cohort A; n = 45) or had a complex karyotype without TP53 mutation (cohort B; n = 13) received entospletinib 400 mg twice daily with decitabine 20 mg/m2 on days 1–10 every 28 days for up to three induction cycles, followed by up to 11 consolidation cycles, in which decitabine was reduced to days 1–5. Entospletinib maintenance was given for up to 2 years. The primary end point was complete remission (CR) and CR with hematologic improvement by up to six cycles of therapy.ResultsThe composite CR rates for cohorts A and B were 13.3% (95% confidence interval, 5.1%–26.8%) and 30.8% (95% confidence interval, 9.1%–61.4%), respectively. The median duration of response was 7.6 and 8.2 months, respectively, and the median overall survival was 6.5 and 11.5 months, respectively. The study was stopped because the futility boundary was crossed in both cohorts.ConclusionsThe combination of entospletinib and decitabine demonstrated activity and was acceptably tolerated in this patient population; however, the CR rates were low, and overall survival was short. Novel treatment strategies for older patients with TP53 mutations and complex karyotype remain an urgent need.

Abstract Asparaginase is a key component of pediatric-inspired regimens in young adults with acute lymphoblastic leukemia (ALL). Truncation of asparaginase therapy is linked to inferior outcomes in children with ALL. However, a similar correlation in adults is lacking. Here, we studied the prevalence and risk factors associated with pegylated (PEG)-asparaginase discontinuation in young adults with ALL treated on the US intergroup Cancer and Leukemia Group B (CALGB) 10403 study and examined the prognostic impact of early discontinuation (ED) (defined as <4 of 5 or 6 planned doses) on survival outcomes. The analysis included 176 patients who achieved complete remission and initiated the delayed intensification (DI) cycle. The median number of PEG-asparaginase doses administered before DI was 5 (range, 1-6), with 57 (32%) patients with ED. The ED patients were older (median, 26 vs 23 years; P = .023). Survival was apparently lower for ED patients compared with those receiving ≥4 doses, but this finding was not statistically significant (hazard ratio [HR], 1.82; 95% confidence interval [CI], 0.97-3.43; P = .06), with corresponding 5-year overall survival (OS) rates of 66% and 80%, respectively. In patients with standard-risk ALL, the ED of PEG-asparaginase adversely influenced OS (HR, 2.3; 95% CI, 1.02-5.22; P = .04) with a trend toward inferior event-free survival (EFS) (HR, 1.84; 95% CI, 0.92-3.67; P = .08). In contrast, there was no impact of early PEG-asparaginase discontinuation on OS (P = .64) or EFS (P = .32) in patients with high-risk disease based on the presence of high-risk cytogenetics, Ph-like genotype, and/or high white blood cell count at presentation. In conclusion, early PEG-asparaginase discontinuation is common in young adults with ALL and may adversely impact survival of patients with standard-risk ALL.

Abstract In this secondary analysis of Hispanic adolescents and young adults (AYA) with acute lymphoblastic leukemia (ALL) treated on Cancer and Leukemia Group B (CALGB) 10403, we evaluated outcomes and geographic enrollment patterns relative to US population data. We used demographic, clinical, and survival data on AYAs enrolled on CALGB 10403 (N = 295, 2007-2012). Surveillance, Epidemiology, and End Results registries provided overall survival (OS) for US AYA ALL by ethnicity/race. North American Association of Cancer Registries provided AYA ALL incidence overall and proportion among Hispanics by US state. Of AYAs enrolled on CALGB 10403, 263 (89%) reported ethnicity/race: 45 (17%) Hispanic, 172 (65%) non-Hispanic White (NHW), 25 (10%) non-Hispanic Black (NHB), and 21 (8%) other. Compared with NHWs, Hispanic and NHB patients had lower household income, and Hispanic patients were more likely to harbor high-risk CRLF2 aberrations. Relative to US estimates, where Hispanic patients represented 46% of newly diagnosed AYA ALL patients and experienced inferior OS compared with NHW (P < .001), Hispanic AYAs on CALGB 10403 did as well as NHW patients (3 year OS, 75% vs 74%; P = NS). Hispanic patients also had higher rates of protocol completion (P = .05). Enrollments on CALGB 10403 differed relative to the distribution of Hispanic AYA ALL in the United States: enrollment was highest in the Midwest; t and only 15% of enrollees were from states with a high proportion of Hispanic AYA ALL patients. In summary, Hispanic patients treated on CALGB 10403 did as well as NHWs and better than population estimates. Geographical misalignment between trial sites and disease epidemiology may partially explain the lower-than-expected enrollment of Hispanic AYA ALL patients.

Abstract Introduction According to population-based Surveillance, Epidemiology and End Results (SEER) cancer registry data, approximately 40% of adolescents and young adults (AYA) with acute lymphoblastic leukemia (ALL) in the United States (U.S.) are Hispanic and 7% are Black and both Hispanic and Black patients have significantly inferior outcomes relative to non-Hispanic Whites (NHW). CALGB 10403, a prospective Phase II clinical trial conducted by the U.S. Intergroup, demonstrated the feasibility of delivering a pediatric-inspired ALL regimen to newly diagnosed AYA ALL patients and found this approach to be superior to historical adult regimens (Stock et al. Blood 2019). In the current analysis, we evaluate enrollment patterns of Hispanic and Black AYAs on CALGB 10403 and compare survival relative to SEER estimates. Methods Demographics on AYAs (18-40 yrs) enrolled on CALGB 10403 (N=295 from 2007-2012) were supplemented with patient-reported education and socioeconomic status (SES) information. Data from the North American Association of Cancer Registries (NAACCR; 2013-2017) were used to evaluate U.S. country-wide ALL incidence (20-49 yrs) overall and among Hispanics, reported per U.S. state. SEER registries (2008-2012) provided racial/ethnic distribution and overall survival (OS) of AYA ALL (15-39 yrs). The distribution of OS was estimated using the Kaplan-Meier method and compared across racial/ethnic groups using log-rank tests. Results Relative to the U.S. AYA ALL population, CALGB 10403 included proportionally fewer Hispanics (41.7% vs. 16.3%, P < 0.001); the distribution of blacks was similar (6.4% vs. 8.5%, P = 0.174). Demographics and ALL characteristics among CALGB 10403 enrollees demonstrated no significant differences in age, sex, cytogenetics, or BMI by race/ethnicity; however, Black AYAs were more likely to have T-ALL, and Hispanic patients were more likely to have Ph-like B-ALL and rearrangements in CRLF2. Hispanic and Black patients reported lower household yearly income, and Black patients had less educational attainment. In order to explore reasons for disproportionately low Hispanic enrollment on CALGB 10403, we calculated the proportion of Hispanic AYAs with ALL relative to the AYA ALL incidence across U.S. states using NAACCR data and compared this with the geographical distribution of CALGB 10403 enrollments. The incidence of AYA ALL across U.S. states is represented in Fig 1A and the proportion of Hispanic AYA ALL patients in Fig 1B. The states with highest proportion of Hispanic patients included CA, TX, and NM, followed by AZ, CO, FL, and NJ. Although CALGB 10403 enrolled patients in 31 U.S. states, the trial did not open in TX or FL. The enrollments numbers were highest across the Mid-Western U.S., with only 47/295 (15.9%) of enrollments coming from the seven states with a high proportion of Hispanic AYA ALL patients (Fig 1C). The 3-yr event-free survival (EFS) and OS for the total CALGB 10403 cohort were 59.1% (53.1%, 65.75%) and 73.5% (68.1%, 79.4%), respectively. Per protocol completion of therapy was highest in Hispanics (75%), relative to Black (64%) and NHW patients (56%), P=0.049. Overall survival among CALGB 10403 participants differed significantly across race/ethnicity (Fig 2), with superior OS experienced by Hispanic patients and inferior OS by Black patients (P= 0.021). These clinical trial results differ from SEER estimates, where both Hispanic and Black patients experience worse OS relative to NHW (Fig 2). Conclusions This in-depth analysis of racial/ethnic enrollments and outcomes on CALGB 10403 uncovered findings that may translate across clinical trials beyond AYA ALL. Importantly, our data suggest that closer matching of trial site selection to geographical racial/ethnic disease incidence may improve minority enrollments on multi-center clinical trials. Relative to NHW, Hispanic patients had superior survival despite having higher rates of Ph-like ALL, indicating that clinical trial participation may mitigate racial/ethnic survival disparities seen in population-based data. Finally, we saw no improvement in trial outcomes among Black AYAs; a deeper understanding of the biological leukemia underpinnings and barriers to successful outcomes would aid future efforts at improving survival across racial/ethnic groups. Figure 1 Figure 1. Disclosures Muffly: Pfizer, Amgen, Jazz, Medexus, Pfizer: Consultancy; Astellas, Jasper, Adaptive, Baxalta: Research Funding; Adaptive: Honoraria, Other: fees for non-CME/CE services: , Research Funding. Advani: Abbvie: Research Funding; Macrogenics: Research Funding; Seattle Genetics: Membership on an entity's Board of Directors or advisory committees, Research Funding; Glycomimetics: Membership on an entity's Board of Directors or advisory committees, Research Funding; Kite Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees, Research Funding; Immunogen: Research Funding; Pfizer: Honoraria, Research Funding; OBI: Research Funding; Amgen: Membership on an entity's Board of Directors or advisory committees, Research Funding. Luger: Syros: Honoraria; Agios: Honoraria; Daiichi Sankyo: Honoraria; Jazz Pharmaceuticals: Honoraria; Brystol Myers Squibb: Honoraria; Acceleron: Honoraria; Astellas: Honoraria; Pfizer: Honoraria; Onconova: Research Funding; Celgene: Research Funding; Biosight: Research Funding; Hoffman LaRoche: Research Funding; Kura: Research Funding. Tallman: NYU Grand Rounds: Honoraria; Syros: Membership on an entity's Board of Directors or advisory committees; Kura: Membership on an entity's Board of Directors or advisory committees; Innate Pharma: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees; Biosight: Membership on an entity's Board of Directors or advisory committees; Roche: Membership on an entity's Board of Directors or advisory committees; Jazz Pharma: Membership on an entity's Board of Directors or advisory committees; Oncolyze: Membership on an entity's Board of Directors or advisory committees; KAHR: Membership on an entity's Board of Directors or advisory committees; Orsenix: Membership on an entity's Board of Directors or advisory committees; Daiichi-Sankyo: Membership on an entity's Board of Directors or advisory committees; Abbvie: Membership on an entity's Board of Directors or advisory committees; Amgen: Research Funding; Rafael Pharmaceuticals: Research Funding; Glycomimetics: Research Funding; Biosight: Research Funding; Orsenix: Research Funding; Abbvie: Research Funding; Mayo Clinic: Honoraria; UC DAVIS: Honoraria; Northwell Grand Rounds: Honoraria; NYU Grand Rounds: Honoraria; Danbury Hospital Tumor Board: Honoraria; Acute Leukemia Forum: Honoraria; Miami Leukemia Symposium: Honoraria; New Orleans Cancer Symposium: Honoraria; ASH: Honoraria; NCCN: Honoraria. Litzow: Omeros: Other: Advisory Board; Jazz: Other: Advisory Board; Pluristem: Research Funding; Actinium: Research Funding; Amgen: Research Funding; AbbVie: Research Funding; Astellas: Research Funding; Biosight: Other: Data monitoring committee. Foster: Macrogenics: Research Funding; Rafael Pharmaceuticals: Research Funding; Macrogenics: Consultancy; Daiichi Sankyo: Consultancy; Agios: Consultancy; Bellicum Pharmaceuticals: Research Funding. Larson: Gilead: Research Funding; Epizyme: Consultancy; Astellas: Consultancy, Research Funding; Rafael Pharmaceuticals: Research Funding; CVS/Caremark: Consultancy; Takeda: Research Funding; Novartis: Research Funding; Cellectis: Research Funding.

Abstract Background: GILT is an oral potent selective FLT3 kinase inhibitor approved for marketing for the treatment (Tx) of patients (pts) with relapsed/refractory FLT3 mutated (FLT3m) AML but efficacy in older ND FLT3m AML pts is unknown. Furthermore, FLT3m can be present as a dominant or subclone and impact of FLT3 inhibitor therapy in this setting is uncertain. Here we report the results of a Phase 2/1b sub-study of the Beat AML Master Trial to assess the efficacy of GILT monotherapy (GILTm) in ND FLT3m AML pts aged ≥60 years with high and low VAF and the subsequent response-driven addition of DEC Tx. (ClinicalTrials.gov NCT03013998) Methods: The study was an open-label multicenter (15 sites), 3-outcome, 2-stage Phase 2 design that assigned pts to either Dominant FLT3/Group 1 (GP1) or Non-Dominant FLT3/Group 2 (GP2) as shown in Figure 1. Key eligibility criteria included ND FLT3m AML pts with high and low VAF and/or ITD ratio, aged ≥60 years, and ECOG performance status 0-2. In the Phase 2 study, all pts received GILTm 120 mg/day on days 1 - 28. Pts without CR/CRi after cycle 2 were transferred to the Phase 1b study to receive GILT + DEC (Figure 1). Phase 1b study utilized a standard 3+3 design to evaluate the safety/tolerability of concurrent GILT + DEC. Pts received GILT (dose level 1 [DL1] = 80 mg/day or dose level 2 [DL2] = 120 mg/day on days 1-28) + DEC 20 mg/m 2 IV on days 1-10 or 1-5 every 28 days. Primary endpoint was CR+CRi rate (Phase 2). Response was assessed using modified 2017 ELN AML criteria. The non-dominant GP2 was stopped for futility, GP1 was stopped early to modify trial to include venetoclax. Results: Phase 2 - Between 9/10/2018 to 2/11/2020, 19 / 20 enrolled pts (GP1: n = 9; GP2: n = 10) received GILTm and were included in analyses. Baseline pt characteristics are shown in Table 1. Median (range) time on GILTm was 3 cycles (1 - 18) in GP1 and 1 cycle (1 - 9) in GP2. Most common reasons for discontinuing Tx were Tx failure (TF; 44%) and relapse (33%) in GP1 and TF (70%) and disease progression (PD; 20%) in GP2. Overall CR+CRi was achieved in 4 pts (44%) in GP1 and 1 pt (10%) in GP2. Response duration are shown in Table 2. After median follow-up of 14.3 months (mos) and 19 mos in GP1 and GP2, respectively, 1-year OS was 56% and 76%. Most common Grade ≥3 adverse events (AEs) were febrile neutropenia and colitis (each 25%) in GP1; anemia and low platelet count in GP2 (each 30%). Overall, 7 pts had 15 serious AEs (SAEs) and all SAEs occurred in GP1 pts; most common SAE was colitis (25%) and 1 pt (13%) had a Tx-related Grade 3 SAE of tumor lysis syndrome. In GP2, 1 pt (10%) had Tx-related Grade 2 AE of differentiation syndrome. In GP1, 2 pts died within 60 days of Tx and none in GP2. Phase1b - After up to 2 cycles of GILTm, 12 pts with no CR/CRi (GP1: n = 4; GP2: n = 8) were transferred to receive GILT + DEC (Figure 1). At the time of this report, 1 pt with CRh remained on Tx. Median total time on Tx (including GILTm) was 4 cycles and median time on GILT + DEC Tx was 3 cycles (Table 2). Most common reasons for discontinuing Tx were PD (33%) and TF (25%); and 2 pts (17%) stopped Tx due to an AE. Pts were treated with DL1 GILT + DEC (n = 3), then DL2 GILT + DEC (n = 9); only 1 pt had dose-limiting toxicity (DLT) at DL2 (Grade 3 hyperbilirubinemia and pneumonitis requiring steroid therapy), hence, DL2 GILT + DEC was considered the MTD. CR+CRi rate was 25% in 3 pts, all at DL2 (Table 2). After a median follow-up of 17.8 mos, the 1-year OS from start of GILT + DEC Tx was 57%. Most common Grade ≥3 Tx-related AEs were anemia, febrile neutropenia and low WBC count (each 22%). Overall, 6 pts had 12 SAEs; 1 pt with SAE of Grade 4 sepsis died. Three GILT-related SAEs occurred in 1 pt - Grade 3 hyperbilirubinemia, and pneumonitis and Grade 1 transaminases increased. One pt died within 30 days and a second within 60 days of Tx. No difference was observed in GILT pharmacokinetics (PK) with or without DEC, however steady state Ctrough values were 1.4 to 2.3-fold greater than in relapsed/refractory AML pts (Admiral trial). Conclusions: In ND pts ≥60 years old with dominant FLT3 AML, GILTm induced a high 44% CR+CRi rate and long median OS (21.7 mos). Pts with non-dominant FLT3 had low 10% CR+CRi rate. GILTm was generally safe and was associated with differentiation syndrome in 1 pt. Concurrent GILT + DEC was acceptably tolerated, only 1 pt had a DLT, and the MTD was 120 mg/day GILT + DEC. A subset of pts with no CR/CRi during GILTm achieved remission with addition of DEC. Based on these results, a triple combination Tx study with venetoclax is currently enrolling. Figure 1 Figure 1. Disclosures Traer: Genentech: Membership on an entity's Board of Directors or advisory committees; Schrodinger: Research Funding; Incyte: Research Funding; Abbvie: Consultancy, Membership on an entity's Board of Directors or advisory committees; Servier/Agios: Membership on an entity's Board of Directors or advisory committees; Astellas: Consultancy, Membership on an entity's Board of Directors or advisory committees; ImmunoGen: Membership on an entity's Board of Directors or advisory committees. Mims: Glycomemetics: Research Funding; Daiichi Sankyo: Consultancy, Research Funding; Aptevo: Research Funding; Leukemia and Lymphoma Society's Beat AML clinical study: Consultancy, Research Funding; Genentech: Consultancy; Xencor: Research Funding; Kartos Pharmaceuticals: Research Funding; Abbvie: Consultancy; BMS: Consultancy; Kura Oncology: Consultancy; Syndax Pharmaceuticals: Consultancy; BMS: Consultancy; Jazz Pharmaceuticals: Consultancy; Aptevo: Research Funding. Stein: Agios Pharmaceuticals, Inc: Consultancy; Novartis: Consultancy; Astellas: Consultancy; Syndax Pharmaceuticals: Consultancy; Daiichi Sankyo: Consultancy; Syros Pharmaceuticals, Inc.: Consultancy; PinotBio: Consultancy; Celgene: Consultancy; Bristol Myers Squibb: Consultancy; Jazz Pharmaceuticals: Consultancy; Foghorn Therapeutics: Consultancy; Blueprint Medicines: Consultancy; Gilead Sciences, Inc.: Consultancy; Abbvie: Consultancy; Janssen Pharmaceuticals: Consultancy; Genentech: Consultancy. Stock: Pfizer: Consultancy, Honoraria, Research Funding; amgen: Honoraria; agios: Honoraria; jazz: Honoraria; kura: Honoraria; kite: Honoraria; morphosys: Honoraria; servier: Honoraria; syndax: Consultancy, Honoraria; Pluristeem: Consultancy, Honoraria. Kovacsovics: AbbVie: Research Funding; Jazz Pharmaceutials: Honoraria; Janssen Pharmaceuticals: Research Funding; Amgen Inc.: Research Funding; Stemline: Honoraria; Novartis: Research Funding. Blum: Xencor: Research Funding; Abbvie: Honoraria; Nkarta: Research Funding; Celyad Oncology: Research Funding; AmerisourceBergen: Honoraria; Forma Therapeutics: Research Funding; Leukemia and Lymphoma Society: Research Funding; Syndax: Honoraria. Arellano: Syndax Pharmaceuticals, Inc: Consultancy; KITE Pharma, Inc: Consultancy. Schiller: Actinium Pharmaceuticals, Inc: Research Funding; Mateon: Research Funding; Tolero: Research Funding; Geron: Research Funding; Regimmune: Research Funding; Kite/Gilead: Honoraria, Research Funding, Speakers Bureau; Celator: Research Funding; Sangamo: Research Funding; Stemline Therapeutics, Inc.: Honoraria, Research Funding, Speakers Bureau; Takeda: Research Funding; PrECOG: Research Funding; Pfizer: Current equity holder in publicly-traded company, Research Funding; Karyopharm: Research Funding; Incyte: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Gamida Cell Ltd.: Research Funding; FujiFilm: Research Funding; Samus: Research Funding; Trovagene: Research Funding; Daiichi-Sankyo: Research Funding; Constellation Pharmaceuticals: Research Funding; BMS/Celgene: Consultancy, Current equity holder in publicly-traded company, Research Funding, Speakers Bureau; Abbvie: Research Funding; Actuate: Research Funding; Arog: Research Funding; Delta-Fly: Research Funding; Amgen: Consultancy, Current equity holder in publicly-traded company, Honoraria, Research Funding, Speakers Bureau; Agios: Consultancy, Research Funding, Speakers Bureau; Novartis: Consultancy, Research Funding; Jazz: Consultancy, Honoraria, Research Funding, Speakers Bureau; Elevate: Research Funding; Ono-UK: Consultancy, Research Funding; Onconova: Research Funding; Deciphera: Research Funding; Astellas: Honoraria, Research Funding, Speakers Bureau; Forma: Research Funding; Genentech-Roche: Research Funding; Bio: Research Funding; Sanofi: Honoraria, Research Funding, Speakers Bureau; Pharma: Consultancy; Johnson & Johnson: Current equity holder in publicly-traded company; Biomed Valley Discoveries: Research Funding; Eli Lilly: Research Funding; ASH foundation: Other: Chair-unpaid; Sellas: Research Funding; Ono: Consultancy; Incyte: Consultancy; Ariad: Research Funding; AstraZeneca: Consultancy; Kaiser Permanente: Consultancy; Cyclacel: Research Funding; MedImmune: Research Funding; Ambit: Research Funding; Leukemia & Lymphoma Society: Research Funding; Bluebird Bio: Research Funding; Boehringer-Ingleheim: Research Funding; Cellerant: Research Funding; CTI Biopharma: Research Funding; Janssen: Research Funding; Kura Oncology: Research Funding; Pharmacyclics: Honoraria, Speakers Bureau; Millennium: Research Funding; National Marrow Donor Program: Research Funding; NIH: Research Funding; Onyx: Research Funding; Pharmamar: Research Funding; UC Davis: Research Funding; UCSD: Research Funding; Evidera: Consultancy; NCI: Consultancy; Novartis: Speakers Bureau. Olin: Astellas: Honoraria, Research Funding; Daiichi Sankyo: Research Funding; Genentech: Research Funding; Pfizer: Research Funding; Cellectis: Research Funding; Amgen: Honoraria; Abbvie: Honoraria; Actinium: Honoraria. Foran: taiho: Honoraria; syros: Honoraria; kura: Research Funding; boehringer ingelheim: Research Funding; sanofi aventis: Honoraria; trillium: Research Funding; aptose: Research Funding; abbvie: Research Funding; pfizer: Honoraria; gamida: Honoraria; actinium: Research Funding; takeda: Research Funding; certara: Honoraria; OncLive: Honoraria; bms: Honoraria; revolution medicine: Honoraria; servier: Honoraria; novartis: Honoraria; h3bioscience: Research Funding; aprea: Research Funding; sellas: Research Funding; stemline: Research Funding. Litzow: AbbVie: Research Funding; Jazz: Other: Advisory Board; Pluristem: Research Funding; Amgen: Research Funding; Omeros: Other: Advisory Board; Actinium: Research Funding; Astellas: Research Funding; Biosight: Other: Data monitoring committee. Lin: AbbVie, Aptevo Therapeutics, Astellas Pharma, Bio-Path Holdings, Celgene, Celyad, Genentech-Roche, Gilead Sciences, Incyte, Jazz Pharmaceuticals, Novartis, Ono Pharmaceutical, Pfizer, Prescient Therapeutics, Seattle Genetics, Tolero, Trovagene: Research Funding. Patel: BMS-Celgene, Agios: Membership on an entity's Board of Directors or advisory committees; Peerview: Honoraria; Aptevo Therapeutics: Research Funding. Foster: Bellicum Pharmaceuticals: Research Funding; Macrogenics: Research Funding; Rafael Pharmaceuticals: Research Funding; Macrogenics: Consultancy; Daiichi Sankyo: Consultancy; Agios: Consultancy. Cogle: Aptevo therapeutics: Research Funding; Celgene: Membership on an entity's Board of Directors or advisory committees. Vergilio: Foundation Medicine: Current Employment. Gana: The Leukemia & Lymphoma Society: Consultancy; Bausch: Current holder of individual stocks in a privately-held company. Druker: VB Therapeutics: Membership on an entity's Board of Directors or advisory committees; The RUNX1 Research Program: Membership on an entity's Board of Directors or advisory committees; GRAIL: Current equity holder in publicly-traded company; Third Coast Therapeutics: Membership on an entity's Board of Directors or advisory committees; EnLiven: Consultancy, Research Funding; Iterion Therapeutics: Membership on an entity's Board of Directors or advisory committees; Recludix Pharma, Inc.: Consultancy; Pfizer: Research Funding; Merck & Co: Patents & Royalties; Cepheid: Consultancy, Membership on an entity's Board of Directors or advisory committees; Novartis Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees, Patents & Royalties; Nemucore Medical Innovations, Inc.: Consultancy; Bristol-Myers Squibb: Research Funding; Blueprint Medicines: Consultancy, Current equity holder in publicly-traded company, Membership on an entity's Board of Directors or advisory committees; Aptose Therapeutics: Consultancy, Current equity holder in publicly-traded company, Membership on an entity's Board of Directors or advisory committees; Amgen: Current equity holder in publicly-traded company, Membership on an entity's Board of Directors or advisory committees; ALLCRON: Consultancy, Membership on an entity's Board of Directors or advisory committees; Aileron: Membership on an entity's Board of Directors or advisory committees; Vincerx Pharma: Current equity holder in publicly-traded company, Membership on an entity's Board of Directors or advisory committees; Vivid Biosciences: Membership on an entity's Board of Directors or advisory committees. Byrd: Novartis, Trillium, Astellas, AstraZeneca, Pharmacyclics, Syndax: Consultancy, Honoraria; Vincerx Pharmaceuticals: Current equity holder in publicly-traded company, Membership on an entity's Board of Directors or advisory committees; Newave: Membership on an entity's Board of Directors or advisory committees. Levine: Auron: Membership on an entity's Board of Directors or advisory committees; Incyte: Consultancy; Ajax: Membership on an entity's Board of Directors or advisory committees; C4 Therapeutics: Membership on an entity's Board of Directors or advisory committees; Isoplexis: Membership on an entity's Board of Directors or advisory committees; Astellas: Consultancy; Celgene: Research Funding; Roche: Honoraria, Research Funding; Zentalis: Membership on an entity's Board of Directors or advisory committees; Prelude: Membership on an entity's Board of Directors or advisory committees; Mission Bio: Membership on an entity's Board of Directors or advisory committees; Amgen: Honoraria; Janssen: Consultancy; Gilead: Honoraria; Morphosys: Consultancy; Imago: Membership on an entity's Board of Directors or advisory committees; QIAGEN: Membership on an entity's Board of Directors or advisory committees; Lilly: Honoraria. Borate: Pfizer: Membership on an entity's Board of Directors or advisory committees, Research Funding; Blueprint Medicine: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees, Research Funding; Genentech: Membership on an entity's Board of Directors or advisory committees, Other: Advisory Board; AbbVie: Membership on an entity's Board of Directors or advisory committees, Research Funding; Jazz Pharma: Research Funding; Daiichi-Sankyo: Membership on an entity's Board of Directors or advisory committees; Takeda: Membership on an entity's Board of Directors or advisory committees; Astellas: Membership on an entity's Board of Directors or advisory committees; incyte: Membership on an entity's Board of Directors or advisory committees, Research Funding; Rampal: Membership on an entity's Board of Directors or advisory committees; Galecto, Inc.: Consultancy; Promedior: Consultancy.