Citations

AbstractWe retrospectively examined our experience with midostaurin therapy in 33 consecutive patients (median age 68 years; 58% females) with advanced systemic mastocytosis (adv‐SM): aggressive SM (ASM; n = 17), SM associated with another hematologic neoplasm (SM‐AHN; n = 14) and mast cell leukemia (MCL; n = 2). KITD816V mutation was detected in 84% of the patients and C findings in 91%. Eleven (33%) patients were previously treated with other cytoreductive drugs, including cladribine (n = 4) and imatinib (n = 3). Median time from diagnosis to initiation of midostaurin therapy was 2.2 months (range 0.3–41). Using modified valent criteria, overall response was 42% (53% ASM, 29% SM‐AHN, 50% MCL; p = .22), all classified as being major. Responses included ≥50% reduction in bone marrow mast cells in 40% and normalization of serum tryptase in 29%, of evaluated cases. After a median follow‐up of 14.6 months from initiation of midostaurin therapy, 7 (21%) deaths, 1 (3%) leukemic progression, and 18 (55%) treatment discontinuations were documented; median duration of midostaurin treatment was 7.9 months (range 0.5–123) and response duration 21.5 months (range 2.9–123). Most frequent side effect was gastrointestinal (51%) while grade 3/4 neutropenia or thrombocytopenia occurred in 12% of patients. Response to treatment was not predicted by KIT mutation (p = .67) or exposure to prior cytoreductive therapy (p = .44). Median survival was longer in midostaurin responders but not significantly (median 26.5 vs. 16 months; p = .15). Findings from the current study are broadly consistent with previously published clinical trial observations.

The NCCN Guidelines for Myelodysplastic Syndromes (MDS) provide recommendations for the evaluation, diagnosis, and management of patients with MDS based on a review of clinical evidence that has led to important advances in treatment or has yielded new information on biologic factors that may have prognostic significance in MDS. The multidisciplinary panel of MDS experts meets on an annual basis to update the recommendations. These NCCN Guidelines Insights focus on some of the updates for the 2022 version of the NCCN Guidelines, which include treatment recommendations both for lower-risk and higher-risk MDS, emerging therapies, supportive care recommendations, and genetic familial high-risk assessment for hereditary myeloid malignancy predisposition syndromes.

AbstractGilteritinib is approved for the treatment of relapsed/refractory (R/R) acute myeloid leukemia (AML) with an FLT3‐mutation (FLT3mut+). However, the gilteritinib phase 3 ADMIRAL study (Perl et al NEJM 2019) was conducted prior to widespread adoption of either midostaurin as a component of standard intensive induction and consolidation or posttransplant FLT3 inhibitor maintenance. We performed a retrospective analysis using data from 11 US centers and where we identified 113 patients who received gilteritinib alone or as combination therapy for the treatment of R/R FLT3mut+ AML. The composite complete remission (CR) rate (CRc, defined as CR + CRi + CR with incomplete platelet recovery [CRp]) was 48.7% (n = 55). The CRc rate after treatment with gilteritinib in patients who were treated with only prior 7+3 and midostaurin with or without consolidation was 58% with a median survival of 7.8 months. Survival was longest in patients who obtained a CR, particularly a cMRD (clinical minimal or measurable residual disease) negative response; this remained significant after censoring at the time of stem cell transplant. The mitogen‐activated protein kinase pathway activating mutations that are known for gilteritinib resistance (NRAS, KRAS, and PTPN11) had lower CRc (35% vs. 60.5%) and lower median overall survival than patients' whose leukemia did not express these mutations (4.9 months vs. 7.8 months) (HR 2.4; 95% CI 1. 5.4) p value <.01.

Abstract Background: Venetoclax, a small-molecule inhibitor of B cell leukemia/lymphoma-2, in combination with hypomethylating agents (HMA) has shown improved efficacy and survival benefit compared to HMA alone (DiNardo et al, 2020) in elderly/unfit patients with acute myeloid leukemia (AML). Since FDA-approval of this regimen for elderly/unfit AML patients, it is frequently utilized both in the upfront and relapsed/refractory setting. Cardiac events with venetoclax are not well described. In the VIALE-E trial, which included patients ineligible for standard induction chemotherapy due to congestive heart failure or stable angina, 15% of patients receiving azacitidine plus venetoclax experienced atrial fibrillation as a serious adverse event, vs. 1% in the azacitidine plus placebo group (DiNardo et al, 2020). Our objective was to provide an estimate of the prevalence of and a description of all cardiac events that occurred in AML patients undergoing treatment with venetoclax + HMA. Methods: 170 consecutive patients with AML who received venetoclax +HMA (azacitidine or decitabine) outside the context of a clinical trial between 1/2017-11/2020 at the Mayo Clinic were included. Patients received venetoclax + HMA either as upfront treatment or for relapsed/refractory disease. Patients with relapse following allogeneic stem cell transplant were excluded. We evaluated all cardiac events that occurred while treatment with venetoclax + HMA was ongoing. Baseline patient and treatment characteristics were compared using the Mann-Whitney U-test and the Fisher's exact test. All statistics were computed using EZR (Version 1.53). Results: 1. Patient characteristics A total of 170 patients who received venetoclax + HMA (median age 69 years [range 17-91], 63% males) were included. ELN risk category was either adverse risk (48%, 82/170) or intermediate risk (48%, 82/170) in the majority of patients. 64% (109/170) of patients received venetoclax + HMA as upfront treatment. Characteristics including age, ELN cytogenetic risk, cardiovascular risk factors, and upfront vs relapsed therapy were similar among patients with or without cardiac events. The only exception was a higher incidence of CEBPA mutation amongst those with cardiac events (12% vs 2%, p=0.03). The majority (83%, 141/170) of patients underwent an echocardiogram prior to initiation of therapy. 2. Cardiac events Of 170 patients treated with venetoclax + HMA during the study period, 34 (20%) patients experienced a total of 48 cardiac events. Of patients experiencing cardiac events, 32% (11/34) had no pre-existing cardiac disease and 12% (4/34) had no cardiovascular risk factors (Table 1). The majority of events occurred early in treatment course: 41% during cycle 1, 26% during cycle 2 and 15% during cycle 3 (Table 1). The most frequently occurring cardiac event (21%, 10/48 events) was a decrease in left ventricular ejection fraction on echocardiography, which was associated with symptoms in all ten patients. Second most frequent was atrial fibrillation with rapid ventricular response at 17% (8/48 events), followed by troponin elevation without electrocardiogram changes at 15% (7/46 events). Of patients with troponin elevation, 57% (4/7 events) occurred in the setting of another inciting factor such as severe anemia, while 43% represented a troponin elevation without explanation (Table 1). Other cardiac events included heart failure with preserved ejection fraction (n=4), other symptomatic arrhythmia (n=4), and symptomatic pericardial effusion or pericarditis (n=3). In addition, 2 of 34 (6%) patients experienced fatal cardiopulmonary arrest. The majority (88%) of cardiac events required either inpatient admission (62%, 21/34 patients) or intensive care unit (ICU) care (26%, 9/34 patients). 77% of patients required new cardiac medications or procedural intervention (n=4). In 27% of cases (9/34 patients), the cardiac event directly contributed to death (Table 1). Conclusions: Cardiac complications were observed in one-fifth (20%) of AML patients treated with venetoclax + HMA, despite the absence of preexisting cardiac disease in a third of cases; moreover 27% of events were fatal. Further comparative studies are required to identify salient clinical features predictive of cardiac complications in these patients. Figure 1 Figure 1. Disclosures Al-Kali: Novartis: Research Funding; Astex: Other: Research support to institution. Litzow: Astellas: Research Funding; Amgen: Research Funding; Omeros: Other: Advisory Board; AbbVie: Research Funding; Actinium: Research Funding; Pluristem: Research Funding; Jazz: Other: Advisory Board; Biosight: Other: Data monitoring committee. Patnaik: Kura Oncology: Research Funding; StemLine: Research Funding.

Abstract Background: Clonal cytopenia of undetermined significance (CCUS) is defined as persistent unexplained cytopenia with evidence of clonality [myeloid-associated somatic mutations (MTs) or cytogenetic [CG] abnormalities] but without definitive evidence of myeloid neoplasms (MN). The outcomes in CCUS patients (pts) are not well understood. Methods: The CCUS International Study database includes pts from 17 institutions who meet the criteria of CCUS and do not have other causes of cytopenia. Pts with MDS defining CG abnormalities were excluded. We collected baseline clinical data, laboratory parameters, CGs, molecular genetics, treatment, and disease course. Diverse gene panels from different institutions were collated to include a total of 70 myeloid-related somatic genes (30 genes in common). 2018 IWG MDS response criteria were used to determine response rate (RR). Disease progression (DP) is defined by progression to MN. The relationship between independent variables and DP and death was assessed using Cox proportional hazards models. Progression-free survival (PFS) and overall survival (OS) were estimated using Kaplan-Meier method. All statistical analysis was performed using SAS. Results: A total of 258 pts were captured by July 2021. The median age was 71 (IQR 63-77) years, and 66% were male. Among 73 (28%) pts with known malignancy history, 27 (37%) pts received previous chemo- or radiation therapy. 27 (10%) pts had non-malignant hematology comorbidities. 91 (35%) had cardiovascular disease, and 33 (13%) had inflammatory disease. (Table 1) The red blood cell and platelet transfusion-dependent rates were 7.3% and 2.3%, respectively. The median number of MTs was 2 (IQR 1-3), with 221 (86%) pts had ≥1 MT, of which 116 (53%) had ≥ 2 MTs. The most common 5 MTs were TET2 (n=78, 30%), SRSF2 (n=50, 19%), DNMT3A (n=47, 18%), ASXL1 (n=40, 16%), and U2AF1 (n=22, 9%) (Figure 1). The median VAF (mVAF) was 28% (IQR: 9.2%, 43%) with VAF &lt; 10% in 47 (18%) and VAF ≥40% in 78 (30.2%) of the MTs. mVAF of the all genes are shown in Figure 2. Among pts with CG abnormalities (n=62, 24%), trisomy 8 and -Y are the most common karyotypes (n=15 for each, 24%) (Table 2). Eighty one (31%) patients received various treatments for CCUS with modest RR, including growth factors (n=47, 18.2%, RR: 25.5%), supportive care (n=23, 9%, RR: 26%), immunoglobulin/immunosuppressive therapy (n=15, 6%, RR: 40%), and DNMTi (n=8, 3%, RR=13%). The median length of follow-up was 15.6 (IQR 6.9-30.6) months. 24 pts progressed to MN, 14 (58.3%) of which were MDS, 8 (33.3%) CMML, and 2 (8.3%) AML. The 2-year PFS was 86.1% (95% CI: 80-93%) with a median PFS of 16.3 (IQR: 3.7, 21) months. In the multivariable model, positive MT of KRAS (HR: 8.4, 95% CI: 1.9-36.9, p=0.005) and CBL (HR: 16.5, 95% CI: 3.7-73.8, p=0.003) were significantly associated with DP. In the functional pathway analysis, having at least 1 splicing factor MT was significantly associated with DP (HR: 2.6, 95% CI:1.2-5.9, p=0.02). TP53 was not significantly associated with DP (HR: 1.2, 95% CI: 0.2-8.7, p=0.88). Having &gt;1 MT (HR: 3.57, 95% CI: 1.19-10.7, p=0.02) compared to a single MT was significantly associated with DP (Figure 3). Over the follow-up period, 35 pts died. The 2-year OS was 81% (95% CI: 74.9-87.9%). In the multivariable model, MT of KRAS (HR: 6.1, 95% CI: 1.8-20, p=0.003), CBL (HR: 7.3, 95% CI: 1.7-31, p=0.007), and FLT3 (HR: 19.9, 95% CI: 2.5-155, p=0.004) were significantly associated with inferior survival. In the functional pathway analysis, MTs in activated signaling pathway were significantly associated with death (HR: 4.1, 95% CI: 1.8-9, p&lt;0.001). None of the pts with TP53 MT died. Having &gt;1 MT was not statistically significantly associated with higher risk of death (HR: 1.5, 95% CI: 0.7-3.0, p=0.28) (Figure 4). After adjustment for co-MT status and comorbidities, baseline Hb&lt;10 g/dL (HR: 3.7, 95% CI: 1.8-7.9, p&lt;0.001) was significantly associated with greater mortality. Conclusion: This large retrospective study summarizes the CCUS pts' characteristics, with different MT patterns and VAF. We confirmed the impact of having &gt;1 MT on DP, but not OS. Genes involved in activated signaling had a significant impact on both DP and OS. TP53 MT was not associated with worse outcome. Findings may be due to limited cases in the particular genes and different gene panels from multiple institutions. A longer follow-up is planned to further describe the predictors for outcome in this ongoing study. Figure 1 Figure 1. Disclosures Komrokji: Jazz: Consultancy, Speakers Bureau; Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; BMSCelgene: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Acceleron: Consultancy; PharmaEssentia: Membership on an entity's Board of Directors or advisory committees; AbbVie: Consultancy; Taiho Oncology: Membership on an entity's Board of Directors or advisory committees; Geron: Consultancy. Zeidan: BioCryst: Other: Clinical Trial Committees; Kura: Consultancy, Other: Clinical Trial Committees; Ionis: Consultancy; Geron: Other: Clinical Trial Committees; Incyte: Consultancy, Research Funding; Amgen: Consultancy, Research Funding; Boehringer Ingelheim: Consultancy, Research Funding; Novartis: Consultancy, Other: Clinical Trial Committees, Travel support, Research Funding; Janssen: Consultancy; Cardiff Oncology: Consultancy, Other: Travel support, Research Funding; Loxo Oncology: Consultancy, Other: Clinical Trial Committees; Aprea: Consultancy, Research Funding; AstraZeneca: Consultancy; Agios: Consultancy; BeyondSpring: Consultancy; Gilead: Consultancy, Other: Clinical Trial Committees; Daiichi Sankyo: Consultancy; Jazz: Consultancy; Astex: Research Funding; BMS: Consultancy, Other: Clinical Trial Committees, Research Funding; Acceleron: Consultancy, Research Funding; Pfizer: Other: Travel support, Research Funding; Genentech: Consultancy; Epizyme: Consultancy; Jasper: Consultancy; Astellas: Consultancy; ADC Therapeutics: Research Funding; AbbVie: Consultancy, Other: Clinical Trial Committees, Research Funding. Madanat: Blue Print Pharmaceutical: Honoraria; Stem line pharmaceutical: Honoraria; Onc Live: Honoraria; Geron Pharmaceutical: Consultancy. Coombs: LOXO: Honoraria, Membership on an entity's Board of Directors or advisory committees; Novartis: Honoraria; AstraZeneca: Honoraria; AbbVie: Honoraria; Genentech: Honoraria; MEI Pharma: Honoraria. Griffiths: Celgene/Bristol-Myers Squibb: Consultancy, Honoraria, Research Funding; Takeda Oncology: Consultancy, Honoraria; Taiho Oncology: Consultancy, Honoraria; Apellis Pharmaceuticals: Research Funding; Novartis: Honoraria; Alexion Pharmaceuticals: Consultancy, Research Funding; Boston Biomedical: Consultancy; Astex Pharmaceuticals: Honoraria, Research Funding; Genentech: Research Funding; Abbvie: Consultancy, Honoraria. Lai: Astellas: Speakers Bureau; Jazz Pharma: Consultancy, Membership on an entity's Board of Directors or advisory committees; Agios: Consultancy, Membership on an entity's Board of Directors or advisory committees; 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; Jazz Pharma: Speakers Bureau; Macrogenics: Consultancy, Membership on an entity's Board of Directors or advisory committees; AbbVie: Consultancy, Membership on an entity's Board of Directors or advisory committees. Foran: trillium: Research Funding; actinium: Research Funding; kura: Research Funding; boehringer ingelheim: Research Funding; takeda: Research Funding; abbvie: Research Funding; aptose: Research Funding; pfizer: Honoraria; novartis: Honoraria; servier: Honoraria; bms: Honoraria; revolution medicine: Honoraria; OncLive: Honoraria; gamida: Honoraria; certara: Honoraria; sanofi aventis: Honoraria; syros: Honoraria; taiho: Honoraria; h3bioscience: Research Funding; aprea: Research Funding; sellas: Research Funding; stemline: Research Funding. Badar: Pfizer Hematology-Oncology: Membership on an entity's Board of Directors or advisory committees. Desai: Astex: Research Funding; Janssen R&D: Research Funding; Kura Oncology: Consultancy; Takeda: Consultancy; Bristol Myers Squibb: Consultancy; Agios: Consultancy. Ades: ABBVIE: Honoraria; CELGENE/BMS: Honoraria; NOVARTIS: Honoraria; TAKEDA: Honoraria; JAZZ: Honoraria, Research Funding; CELGENE: Research Funding. Brunner: Novartis, Celgene, Takeda, AstraZeneca: Research Funding; Celgene, Forty Seven Inc, Jazz: Other: Advisory Board. Carraway: Celgene, a Bristol Myers Squibb company: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Takeda: Other: Independent review committee; Stemline: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; AbbVie: Other: Independent review committee; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Jazz: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Agios: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Astex: Other: Independent review committee; Bristol Myers Squibb: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Prebet: BMS: Research Funding; BMS, Curios, Daichi: Consultancy. Patnaik: Kura Oncology: Research Funding; Stemline Therapeutics: Membership on an entity's Board of Directors or advisory committees; Stemline Therapeutics: Membership on an entity's Board of Directors or advisory committees. Savona: Karyopharm: Consultancy, Current equity holder in publicly-traded company, Membership on an entity's Board of Directors or advisory committees; Geron: Consultancy, Membership on an entity's Board of Directors or advisory committees; CTI: Consultancy, Membership on an entity's Board of Directors or advisory committees; BMS-Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees; NOVARTIS: Consultancy, Membership on an entity's Board of Directors or advisory committees; Ryvu: Consultancy, Membership on an entity's Board of Directors or advisory committees; Sierra Oncology: Consultancy, Membership on an entity's Board of Directors or advisory committees; Taiho: Consultancy, Membership on an entity's Board of Directors or advisory committees; TG Therapeutics: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Takeda: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; ALX Oncology: Research Funding; Astex: Research Funding; Incyte: Research Funding. Al-Kali: Novartis: Research Funding; Astex: Other: Research support to institution.

Abstract Introduction: Clonal hematopoiesis of indeterminate potential (CHIP) is defined by the presence and subsequent expansion of leukemia-associated driver mutations (MT). These MT predominantly involve epigenetic regulators such as DNMT3A, ASXL1, and TET2 (DAT, 75%). CHIP is a disease of aging and is associated with increased all-cause mortality. Clonal Hematopoiesis (CH), when present in the context of unexplained cytopenias and MT variant allele fractions (VAF) &gt;20%, is termed as clonal cytopenias of undetermined significance (CCUS). Chronic myelomonocytic leukemia (CMML) is a hematological malignancy characterized by TET2, ASXL1, and SRSF2MT as well as sustained monocytosis. It usually arises in the setting of existing CH and clonal monocytosis. Here, we assessed the clonal compositions involving DAT genes in patients (pts) with CHIP, CCUS, and CMML. Methods: We included 1008 pts: 54 (5%) with CHIP, 334 (33%) with CCUS, and 620 (62%) with CMML. Demographics, laboratory parameters, and mutational spectrum at diagnosis were collected. We characterized and compared DAT MT in all three cohorts and assessed correlations with clinical parameters. MT locus and type along with protein sequences were analyzed using ProteinPaint. All statistical analyses were performed using R. Results: Of the 1008 pts, 427 (42%) had DAT MT; 36 had CHIP (67%); 96 had CCUS (29%), and 296 had CMML (48%). The median age was 71 years (IQR 65-76), and 68% were male. CMML pts had higher white blood cell counts, absolute neutrophil counts, absolute monocyte counts, and lower hemoglobin and platelet counts in comparison to CCUS and CHIP pts. The distribution of age and sex were similar among the three groups. After a median follow-up of 11 months (IQR 9.5-12.8), there were no myeloid progressions in the CHIP group and 17 (18%) in the CCUS group (8 of which developed CMML, Table 1). There were 738 protein-altering or splice-site DATMT in 495 unique MT hotspots. Pts with TET2MT were older (71 years, compared to DNMT3AMT: 69 years and ASXL1MT: 69 years , p&lt;0.022). ASXL1MT were more common in males (75%, compared to DNMT3AMT: 52% and TET2MT: 66%, p=0.005). The mean VAF (mVAF) were 15.5% for DNMT3AMT, 35% for ASXL1MT and 39.2% TET2MT, respectively (p&lt;0.001). We then compared DATMT characteristics in CHIP, CCUS, and CMML groups: DNMT3AMT were most common in CHIP, followed by CCUS, and were very rare in CMML (35% vs. 15% vs. 3%, p&lt;0.001), with mVAF of DNMT3AMT increasing across this spectrum (CHIP: 6.5% vs. CCUS: 17.1% vs. CMML: 43.4%, p&lt;0.0001). While DNMT3A missense MTs were most common (n=62, 67.4%), the AML-associated R882 hotspot MT was seen in 26 (28%) pts (CHIP: n=3, 5%, CCUS: n=10, 16%, and CMML n=13, 21%, Figure 1a). None of the DNMT3AMT CHIP and CCUS pts progressed to CMML.ASXL1MT were most frequently seen in CMML (n=178, 28.6%), followed by CHIP (n=4, 7.4%), and CCUS (n=17, 5%, p&lt;0.001). The mVAF of ASXL1MT was significantly lower in CHIP, followed by CCUS, and CMML (11% vs. 34% vs. 36%, p&lt;0.0001). Truncating ASXL1 MTs were most common (n=205, 53%). Mutational hotspots included G646W (n=81, CCUS: n=6, 3%, CMML: n=75, 37%) and E635 (n=27, CHIP: n=1, 0.5%, CCUS: n=1, 0.5%, CMML: n=27, 13%, Figure 1b). Four ASXL1MT CCUS pts transformed to CMML (R965, E635, G646W, Q910*, and Q925*); of which 2 co-mutated with TET2MT, one with SRSF2MT, and one with an additional ASXL1MT.TET2MT were frequently encountered in CMML, followed by CCUS and CHIP pts (CMML: n=205, 33% vs. CCUS: n=88, 26.3% vs. CHIP: n=15, 27.8%, p=0.02). The mVAF of TET2MT progressively increased across the 3 groups (CHIP: 14.1%, CCUS: 31.9%, CMML: 45.5%, p&lt;0.001). TET2MT occurred across the span of the gene, with no clear hotspots identified, with nonsense MT being most frequent (n=150, 37.3%, Figure 1c). Among the nonsense and frameshift TET2MT (n=209), 131 (63%) involved the N terminal region, and 78 (37%) involved the catalytic domain. Among 8 CCUS pts that transformed to CMML, 6 had TET2MT, including 4 with spliceosome co-MT. Conclusion: While CMML, a disease of aging, arises in the background of CH, the most common CH MT, DNMT3AMT, plays a minor role in this process, and in fact, DNMT3AMT tend to occur at younger ages. While DNMT3A MT and ASXL1MT are preferentially observed in hotspots, TET2MT span the entire gene. Clonal compositions largely involving truncating TET2MT and frameshift ASXL1MT, in conjunction with splicing MT, shape the CMML genotype. Figure 1 Figure 1. Disclosures Komrokji: Geron: Honoraria; Novartis: Honoraria; Agios: Honoraria, Speakers Bureau; Abbvie: Honoraria, Speakers Bureau; JAZZ: Honoraria, Speakers Bureau; BMS: Honoraria, Speakers Bureau; Acceleron: Honoraria. Zeidan: Genentech: Consultancy; BeyondSpring: Consultancy; Kura: Consultancy, Other: Clinical Trial Committees; Amgen: Consultancy, Research Funding; Cardiff Oncology: Consultancy, Other: Travel support, Research Funding; Astex: Research Funding; Epizyme: Consultancy; Geron: Other: Clinical Trial Committees; Boehringer Ingelheim: Consultancy, Research Funding; AstraZeneca: Consultancy; Acceleron: Consultancy, Research Funding; Astellas: Consultancy; Novartis: Consultancy, Other: Clinical Trial Committees, Travel support, Research Funding; Agios: Consultancy; Aprea: Consultancy, Research Funding; AbbVie: Consultancy, Other: Clinical Trial Committees, Research Funding; Loxo Oncology: Consultancy, Other: Clinical Trial Committees; Pfizer: Other: Travel support, Research Funding; ADC Therapeutics: Research Funding; Gilead: Consultancy, Other: Clinical Trial Committees; BMS: Consultancy, Other: Clinical Trial Committees, Research Funding; Jazz: Consultancy; Incyte: Consultancy, Research Funding; Ionis: Consultancy; Jasper: Consultancy; Daiichi Sankyo: Consultancy; Janssen: Consultancy; BioCryst: Other: Clinical Trial Committees. Coombs: LOXO: Honoraria, Membership on an entity's Board of Directors or advisory committees; Novartis: Honoraria; AstraZeneca: Honoraria; AbbVie: Honoraria; Genentech: Honoraria; MEI Pharma: Honoraria. Madanat: Blue Print Pharmaceutical: Honoraria; Stem line pharmaceutical: Honoraria; Onc Live: Honoraria; Geron Pharmaceutical: Consultancy. Griffiths: Takeda Oncology: Consultancy, Honoraria; Novartis: Honoraria; Taiho Oncology: Consultancy, Honoraria; Apellis Pharmaceuticals: Research Funding; Alexion Pharmaceuticals: Consultancy, Research Funding; Boston Biomedical: Consultancy; Astex Pharmaceuticals: Honoraria, Research Funding; Celgene/Bristol-Myers Squibb: Consultancy, Honoraria, Research Funding; Genentech: Research Funding; Abbvie: Consultancy, Honoraria. Lai: Jazz Pharma: Consultancy, Membership on an entity's Board of Directors or advisory committees; Astellas: Speakers Bureau; Jazz Pharma: Speakers Bureau; Macrogenics: 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; Agios: Consultancy, Membership on an entity's Board of Directors or advisory committees; Genentech: Consultancy, Membership on an entity's Board of Directors or advisory committees; AbbVie: Consultancy, Membership on an entity's Board of Directors or advisory committees. Savona: CTI: Consultancy, Membership on an entity's Board of Directors or advisory committees; Geron: Consultancy, Membership on an entity's Board of Directors or advisory committees; Karyopharm: Consultancy, Current equity holder in publicly-traded company, Membership on an entity's Board of Directors or advisory committees; BMS-Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees; NOVARTIS: Consultancy, Membership on an entity's Board of Directors or advisory committees; Ryvu: Consultancy, Membership on an entity's Board of Directors or advisory committees; Sierra Oncology: Consultancy, Membership on an entity's Board of Directors or advisory committees; Taiho: Consultancy, Membership on an entity's Board of Directors or advisory committees; TG Therapeutics: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Takeda: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; ALX Oncology: Research Funding; Astex: Research Funding; Incyte: Research Funding. Litzow: AbbVie: Research Funding; Actinium: Research Funding; Pluristem: Research Funding; Amgen: Research Funding; Astellas: Research Funding; Jazz: Other: Advisory Board; Omeros: Other: Advisory Board; Biosight: Other: Data monitoring committee. Al-Kali: Novartis: Research Funding; Astex: Other: Research support to institution. Patnaik: StemLine: Research Funding; Kura Oncology: Research Funding.