Podoltsev, Nikolai

Introduction: Myelofibrosis (MF) is a clonal hematologic malignancy characterized by constitutive JAK-STAT activation and aberrant cytokine signaling. Allogeneic hematopoietic stem cell transplantation (allo-HCT) remains the only potentially curative therapy in MF. The contribution of disease-, patient- and donor-related factors to allo-HCT outcomes remains to be fully elucidated, as well as the presence of somatic mutations in genes such as ASXL1, EZH2, SRSF2, U2AF1 and IDH1/2 which are associated with worse prognosis in MF patients (pts). In this large multi- center retrospective analysis, we aimed to study the impact of clinical and molecular mutations on transplant outcomes. Methods: This analysis including 498 pts from 11 centers in North America and Canada. Univariate proportional-hazard Cox regression analysis stratified by center was used to assess the association of patient, transplant, and disease characteristics on overall survival (OS). Baseline patient demographic data and disease characteristics were selected as covariates in the multivariate analysis. Results: Pts transplanted between 2002-2021 were included in this analysis. Baseline and transplant characteristics are summarized in table 1. The 1- and 2-year OS was 77% (95% CI; 73-81) and 70% (95% CI; 66-74) and non-relapse mortality (NRM) 19% (95% CI: 17-21) and 23% (95% CI: 19-27), respectively. The cumulative incidence (CMI) of relapse at 1- and 2-years was 12% (95% CI; 10-14) and 16% (95% CI; 12-20). The CMI of acute graft versus host disease (aGVHD) grade II-IV was 31% (95% CI; 27-35) at 3 months and 42% (95% CI; 38-46) at 1-year post-transplant and grade was III-IV 13% (95% CI; 11-15) and 18% (95% CI; 14-22), respectively. The CMI of neutrophil engraftment at 1 and 3 months was 90% (95% CI: 87-93) and 97% (95% CI: 95-95) and for platelets 55% (95% CI: 50-59) and 80% (95% CI: 76-83). Univariate analysis included pts (age and gender), transplant (donor type and conditioning regimen intensity) and disease characteristics (DIPSS, mutations, cytogenetics (CG), blood counts, and spleen size). Hemoglobin > 10 g/dL (HR .5, 95% CI .34 -.73 p=3 x 10 -4) and platelets >50× 10 9/L (HR .59, 95% CI .42-.81, p=.0013) prior to transplant were associated with improved OS. High risk DIPSS was associated with decreased OS (p=0.0002). Mutations in ASXL1, EZH2, IDH1/2, U2AF1 and SRSF2 were not associated with decreased OS in this analysis (Figure 1). However, mutations in ZRSR2 were associated with inferior OS (HR 2.07, 95% CI 1.08-3.95, p=.0252). Lastly, JAK2 which had the most frequent mutations was not associated with OS (HR .0.93, 95% CI .65-1.31). There was no association between the CG risk groups and OS. Splenomegaly, measured radiographically, had no impact on OS but was strongly associated with engraftment (better engraftment defined as HR>1). For platelets, spleen size of 15.6-18.9 cm HR of 0.69 (95% CI .47-1, p=.0489) and size >18.9-22.5 cm HR of 0.48 ( 95% CI .33-.7, p=1x10^-4). For neutrophils, spleen size >19.9-22.5 cm had a HR of 0.68, (95% CI .48-.96, p=.0268) and size>22.5 cm had a HR of 0.65 (95% CI .46-.91, p=.0114). Mismatched unrelated (MMURD) and haplo identical donors had no impact on survival but were associated with delayed platelet engraftment; MMURD (HR .67, 95% CI .47-.96, p=.0298) and haploidentical donors (HR .56, 95% CI .39-.8, p=.0017). In a multivariate analysis adjusted for age, gender, highest DIPSS, donor type and conditioning regimen, platelets > 50× 10 9/L (HR .61, 95% CI .44-.87, p=.0053) hemoglobin >10 g/dL (HR .6, 95% CI .4-.9, p=.0244) and lower DIPSS at the time of transplant were associated with improved OS. Conclusions: In this large multicenter analysis only clinical variables; hemoglobin and platelets, were found to be associated with OS after allo-HCT in MF patients. Somatic mutations associated with poor prognosis were not associated with OS suggesting that transplant can overcome their negative impact. Splenomegaly was associated with delayed engraftment but not OS. Interestingly, using alternative donors (MMURD and haplo identical) didn't have a negative effect on OS, possibly reflecting the use of post-transplant cyclophosphamide for GVHD prophylaxis in recent years. These results highlight the importance of biologic factors in the prognostication of outcomes in MF pts undergoing allo-HCT independent of somatic mutations. Supported by the American Society of Hematology (ASH) and MPN Research Foundation

The classic Philadelphia chromosome–negative myeloproliferative neoplasms (MPN) consist of myelofibrosis, polycythemia vera, and essential thrombocythemia and are a heterogeneous group of clonal blood disorders characterized by an overproduction of blood cells. The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for MPN were developed as a result of meetings convened by a multidisciplinary panel with expertise in MPN, with the goal of providing recommendations for the management of MPN in adults. The Guidelines include recommendations for the diagnostic workup, risk stratification, treatment, and supportive care strategies for the management of myelofibrosis, polycythemia vera, and essential thrombocythemia. Assessment of symptoms at baseline and monitoring of symptom status during the course of treatment is recommended for all patients. This article focuses on the recommendations as outlined in the NCCN Guidelines for the diagnosis of MPN and the risk stratification, management, and supportive care relevant to MF.

Abstract Background The National Institutes of Health define African Americans or Blacks, American Indians, Alaska Natives, Hispanics or Latinos, Native Hawaiians, and other Pacific Islanders as being underrepresented in medicine. A number of studies have demonstrated that improving diversity of such underrepresented demographics within the medical profession improves patient outcomes, medical education and reduces health disparities in patients from vulnerable racial or socioeconomic groups. Despite this recognition, significant underrepresentation of various racial, ethnic, and sexual identities still exists within nearly all medical specialties. Aims The purpose of this study was to a gain a greater understanding of the current state of diversity, equity, and inclusion (DEI) efforts among U.S. hematology and medical oncology fellowship training programs. We explored the perspectives of adult and pediatric fellowship program directors regarding current recruitment strategies and suggestions for improvement to help mitigate the effects of implicit and explicit bias. Here, we present an interim analysis of the data using descriptive statistics. Methods: We convened a multi-institutional collaboration of fellowship program directors, teaching faculty, and staff members of the American Society of Hematology to develop a survey examining perceptions of DEI efforts among hematology and medical oncology fellowship program directors. The survey was pilot tested in a small group of program directors representing 6 different academic programs (5 adult, 1 pediatric). The final online survey was distributed via email to 224 fellowship program directors at U.S. adult and pediatric hematology and medical oncology fellowship programs. The survey included 29 questions regarding perspectives on bias within the fellowship selection process, current DEI initiatives, and current faculty and fellow demographics. Survey respondents were asked to rate the importance of numerous factors in determining which applicants to invite utilizing a scale of 0-10, with 0 and 10 representing lowest and highest importance, respectively. To measure program director perceptions of certain applicant groups, survey respondents were asked to rate applicant demographics as being advantaged/disadvantaged based on survey options ranging from 0-5, with 0 and 5 representing very disadvantaged and very advantaged, respectively. Results: At interim analysis, 41 of 224 program directors completed the survey for an interim response rate of 21%, including 25 adult program directors and 16 pediatric program directors, with representation from university and community programs. Of the program directors surveyed, 28 (68%) reported having access to a dedicated diversity committee or DEI policies in place to improve recruitment of underrepresented applicants. In determining which applicants to invite, respondents placed highest value on the applicant's program director letter (mean score ± standard deviation: 7.44±1.93), caliber of the applicant's residency program (7.28±2.06) and letters of recommendations (7.15±2.23). Survey respondents viewed white and male applicants as representing the most advantaged demographic group, while LGBTQI, age>40, and U.S. citizen and non-citizen international medical graduates were the most disadvantaged (Table 1). Suggestions regarding improving DEI in the fellowship selection process included implementing bias training, identifying potentially disadvantaged applicants in ERAS, increasing faculty diversity, and pairing underrepresented applicants with interviewers based on applicant preference. Conclusion: While the majority of hematology and medical oncology fellowship program directors report having DEI programs or policies to improve recruitment of underrepresented applicants, perceptions of advantaged/disadvantaged groups may extend beyond demographics traditionally viewed as being underrepresented in medicine. As our survey is ongoing, we plan to reanalyze our data when the survey has been finalized with a higher response rate utilizing multivariable regression to identify themes that may further improve DEI efforts within the fellowship selection process. Figure 1 Figure 1. Disclosures LaCasce: Bristol-Myers Squibb Company.: Other: Data Safetly and Monitoring. Murphy: North American Thrombosis Foundation: Honoraria. Naik: Rigel: Research Funding. Podoltsev: Pfizer: Honoraria; Blueprint Medicines: Honoraria; Incyte: Honoraria; Novartis: Honoraria; Celgene: Honoraria; PharmaEssentia: Honoraria; Bristol-Myers Squib: Honoraria; CTI BioPharma: Honoraria.

Abstract Background: Relapsed or refractory (R/R) acute lymphoblastic leukemia (ALL) or lymphoblastic lymphoma (LL) remain a therapeutic challenge, especially in elderly patients(pts) or those with T-cell immunophenotype. Inhibition of apoptosis is an increasingly recognized mechanism for resistance to conventional chemotherapy. Recently, the oral bcl-2 inhibitor venetoclax (VEN) has shown remarkable activity in a variety of hematologic malignancies. Preclinical data in both B- and T-ALL suggests synergy of VEN with vincristine(VCR). Liposomal VCR (L-VCR) is FDA approved for relapsed ALL having progressed following 2 or more antileukemia therapies. We designed a phase I/II trial (EA9152) of the combination of L-VCR and VEN for pts with r/r B-or T-cell ALL or LL. Here, we report for the first time the safety and efficacy outcomes of the phase I portion of this trial (NCT03504644). Methods: This open-label phase I/II study enrolled pts age>=18 with ALL or LL who were R/R to multiagent chemotherapy. Subjects could have received prior VCR or VEN . In a standard 3 + 3 dose escalation design, subjects were given a two week lead-in phase of single agent VEN in the following schedule: dose level 1 - 20, 50, 100, 200 mg on days 1, 2, 3, 4 and 400 mg on days 5 ‒ 42; dose level 2 - 50, 100, 200, 400 mg on days 1, 2, 3, 4 and 600 mg on days 5 ‒ 42; and dose level 3 ‒ 100, 200, 400, 600 mg on days 1, 2, 3, 4 and 800 mg on days 5 ‒ 42. Weekly L-VCR 2.25mg/m 2 IV was started on D15 of cycle 1, and starting day 1 for subsequent cycles (cycle 2+ = 28 days). For cycle 2 and beyond, VEN 400mg, 600mg, or 800mg based on dose level was given starting on day 1 of the cycle. Primary objective of the phase I portion was to determine the maximum tolerated dose (MTD) of VEN in combination with L-VCR. Secondary objectives included determining preliminary response rates. Results: EA9152 was activated on April 26, 2018 and the phase I portion closed to accrual on March 2, 2021. Among the 18 pts in dose escalation (Table 1), the median age was 42 years (22-77). The majority of pts were male (56%), white (80%), and with a performance status (PS) of 1 (78%). Among 13 pts with disease diagnosis reported, 9 had ALL and 4 had LL. Seventeen of 18 (94%) reported previous chemotherapy, two of which had previous stem cell transplant. Median treatment cycles received is 1 (range 1-11). One patient, having received 11 cycles, remains on study at the time of data analysis. Grade >=3 treatment-related adverse events were reported in 89% of treated pts, with neutrophil count decreased (67%), white blood cell decreased (56%), and anemia (50%) as the most common. One pt experienced grade 3 tumor lysis syndrome. Twelve pts were considered evaluable for MTD determination. Six pts were considered not evaluable for toxicity analysis on account of withdraw of consent for treatment (n=4) or rapid disease progression (n=2). Two pts (2 of 3) at dose level 3 experienced DLTs, one each of hypokalemia and heart failure. Therefore, the MTD of the combination was determined to be dose level 2 - VEN 50, 100, 200, 400 mg on days 1, 2, 3, 4 and 600 mg on days 5 ‒ 42 and for subsequent cycles, with L-VCR 2.25mg/m2 IV weekly. In regards to best overall responses observed (Table 2) 4 of 18 pts (22%) achieved complete response (CR), 4 patients (22%) had stable disease, and 7 (39%) had progressive disease. Two patients in CR were found to be measurable residual disease (MRD) negative as well. Conclusions: In the phase 1 portion of this study, the combination of VEN and L-VCR was found to be safe for patients with ALL and LL. The MTD of the combination was found to be VEN 600mg daily with encouraging preliminary efficacy seen including MRD negative responses. The phase 2 portion of this trial is actively enrolling with VEN 600mg daily starting C1D1. Figure 1 Figure 1. Disclosures Palmisiano: Takeda: Consultancy; Genentech: Research Funding; Foundation One: Consultancy; AbbVie: Consultancy, Research Funding. Claxton: Astellas: Other: Clinical Trial; Novartis: Research Funding; Astex: Research Funding; Cyclacel: Research Funding; Daiichi Sankyo: Research Funding; Incyte: Research Funding. Park: BMS: Consultancy; Amgen: Consultancy; Autolus: Consultancy; Novartis: Consultancy; Minerva: Consultancy; PrecisionBio: Consultancy; Curocel: Consultancy; Artiva: Consultancy; Kite Pharma: Consultancy; Kura Oncology: Consultancy; Affyimmune: Consultancy; Servier: Consultancy; Innate Pharma: Consultancy; Intellia: Consultancy. Podoltsev: Novartis: Honoraria; Incyte: Honoraria; Celgene: Honoraria; Pfizer: Honoraria; Blueprint Medicines: Honoraria; Bristol-Myers Squib: Honoraria; PharmaEssentia: Honoraria; CTI BioPharma: Honoraria. Atallah: Novartis: Consultancy, Honoraria, Research Funding; Pfizer: Consultancy, Research Funding; BMS: Honoraria, Speakers Bureau; Takeda: Consultancy, Research Funding; Abbvie: Consultancy, Speakers Bureau; Amgen: Consultancy. Dinner: Kite/Gilead: Consultancy, Honoraria; Pfizer: Consultancy, Honoraria. Webster: AmGen: Consultancy; Pfizer: Consultancy. 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. Litzow: AbbVie: Research Funding; Astellas: Research Funding; Amgen: Research Funding; Actinium: Research Funding; Pluristem: Research Funding; Jazz: Other: Advisory Board; Omeros: Other: Advisory Board; Biosight: Other: Data monitoring committee. OffLabel Disclosure: Venetoclax, a BCL-2 inihibitor, is not FDA-approved for use in ALL.

BackgroundThe availability of novel agents (NAs), including blinatumomab and inotuzumab ozogamicin (InO), has improved the outcomes of patients with relapsed/refractory (RR) B‐cell acute lymphoblastic leukemia (ALL). Because of the relative effectiveness, it is often a challenge for clinicians to determine how to best sequence these NAs with respect to efficacy and toxicity.MethodsIn this multicenter, retrospective study of patients with RR ALL treated with blinatumomab, InO, or both, their efficacy as a first or second NA was compared.ResultsAmong 276 patients, 221 and 55 received blinatumomab and InO, respectively, as a first NA therapy. The complete remission (CR)/complete remission with incomplete count recovery (CRi) rate was 65% and 67% for the blinatumomab and InO groups, respectively (P = .73). The rate of treatment discontinuation due to adverse events was 4% and 7% in the blinatumomab and InO groups, respectively. Ninety‐two patients (43%) in the blinatumomab group and 13 patients (29%) in the InO group proceeded with allogeneic hematopoietic stem cell transplantation. The median overall survival (OS) was 15 and 11.6 months in the blinatumomab and InO groups, respectively. A subset analysis was performed for 61 patients who received both NAs (blinatumomab and then InO [n = 40] or InO and then blinatumomab [n = 21]). The CR/CRi rate was 58% for patients who received InO as the second NA and 52% for patients who received blinatumomab as the second NA. The median OS was 10.5 for patients who received InO as the second NA and 5.9 months for patients who received blinatumomab as the second NA (P = .09).ConclusionsAlthough the limited power of this study to detect a significant difference between subgroups is acknowledged, the data suggest that blinatumomab and InO may have comparable efficacy as a first or second NA therapy in RR ALL.

Eosinophilic disorders and related syndromes represent a heterogeneous group of neoplastic and nonneoplastic conditions, characterized by more eosinophils in the peripheral blood, and may involve eosinophil-induced organ damage. In the WHO classification of myeloid and lymphoid neoplasms, eosinophilic disorders characterized by dysregulated tyrosine kinase (TK) fusion genes are recognized as a new category termed, myeloid/lymphoid neoplasms with eosinophilia and rearrangement of PDGFRA , PDGFRB or FGFR1 or with PCM1-JAK2 . In addition to these aforementioned TK fusion genes, rearrangements involving FLT3 and ABL1 genes have also been described. These new NCCN Guidelines include recommendations for the diagnosis, staging, and treatment of any one of the myeloid/lymphoid neoplasms with eosinophilia (MLN-Eo) and a TK fusion gene included in the 2017 WHO Classification, as well as MLN-Eo and a FLT3 or ABL1 rearrangement.

Abstract The availability and use of blinatumomab symbolizes a paradigm shift in the management of B-cell acute lymphoblastic leukemia (ALL). We conducted a retrospective multicenter cohort analysis of 239 ALL patients (227 relapsed refractory [RR], n = 227; minimal residual disease [MRD], n = 12) who received blinatumomab outside of clinical trials to evaluate safety and efficacy in the “real-world” setting. The median age of patients at blinatumomab initiation was 48 years (range, 18-85). Sixty-one (26%) patients had ≥3 prior therapies and 46 (19%) had allogeneic hematopoietic cell transplantation before blinatumomab. The response rate (complete remission/complete remission with incomplete count recovery) in patients with RR disease was 65% (47% MRD−). Among 12 patients who received blinatumomab for MRD, 9 (75%) patients achieved MRD negativity. In patients with RR disease, median relapse-free survival and overall survival (OS) after blinatumomab was 32 months and 12.7 months, respectively. Among patients who received blinatumomab for MRD, median relapse-free survival was not reached (54% MRD− at 2 years) and OS was 34.7 months. Grade ≥3 cytokine release syndrome, neurotoxicity, and hepatotoxicity were observed in 3%, 7%, and 10% of patients, respectively. Among patients who achieved complete remission/complete remission with incomplete count recovery, consolidation therapy with allogeneic hematopoietic cell transplantation retained favorable prognostic significance for OS (hazard ratio, 0.54; 95% confidence interval, 0.30-0.97; P = .04). In this largest “real-world” experience published to date, blinatumomab demonstrated responses comparable to those reported in clinical trials. The optimal sequencing of newer therapies in ALL requires further study.

Key Points A mixed methods study of surveys, interviews, and focus groups raises concerns about the state of the adult hematology workforce. Hematology/oncology fellowship program directors, fellows, and practicing clinicians offer different strategies to address these problems.

Background: Inotuzumab ozogamicin (InO) is an antibody-drug conjugate composed of anti-CD22 antibody conjugated to the cytotoxic agent calicheamicin, which is approved for relapsed/ refractory (RR) B-cell acute lymphocytic leukemia (ALL), based on efficacy demonstrated in a randomized control trial. We sought to investigate the safety and efficacy of InO in the "real world" setting. Methods: We conducted a retrospective multicenter study in collaboration with 11 U.S. academic institutions, and evaluated the outcome of patients (pts) with RR B-cell ALL, who received InO outside of clinical trials. These pts were evaluated for response to InO, duration of response, overall survival (OS) and toxicity. Demographic and disease characteristics were summarized using descriptive statistics. Survival curves were estimated using the Kaplan-Meier method and compared via log-rank test. Duration of response was estimated among pts who achieve complete remission (CR)/CR with incomplete count recovery (CRi). Results: From June 2016 to May 2019, 84 pts with RR-B cell ALL were identified. Baseline characteristics are summarized in Table 1. The median age of pts at InO initiation was 50 years (yrs) (range, 20-87). Twenty-two (27.5%) pts had t(9;22) (Ph+ve) and 6 (7.5%) pts had t(4;11) (MLL gene) chromosomal abnormalities. Nine (11%) and 20 (25%) pts had CNS disease at diagnosis and at relapse, respectively. Median number of therapies prior to InO was 2 (range, 0-7), 40 (48%) pts had ≥ 3 therapies and 23 (27%) pts had allogeneic stem cell transplantation (allo-HCT) prior to InO. Forty (48%) pts received blinatumomab prior to InO. Fourteen (17%) pts received InO in combination with chemotherapy and/ or tyrosine kinase inhibitor (TKI). Overall response rate (CR/CRi) was 63%; 44% had CR with minimal residual disease (MRD) negativity by flow cytometry. Response rate in Ph+ve B-cell ALL was 73%. Twenty-three (27%) pts were successfully bridged to allo-HCT. Median response duration with InO was 11.5 months (mo); 32.5% had sustained response at 2 yrs (Fig. 1a). Median response duration post InO, censored at allo-HCT was not reached (NR) (51% in remission at 2 yrs) (Fig. 1b). Median OS after InO was 11.6 mo and 32% were alive at 2 yrs (Fig. 1c). Median OS post InO, censored at of allo-HCT was 13.6 mo (Fig. 1d). Median OS after InO in Ph+ve pts was NR (71% alive at 1 yr). Forty-nine percent, 27%, 6% and 5% of pts discontinued InO due to progression, allo-HCT, adverse events and maintenance therapy, respectively. Nineteen (30%) pts had dose interruptions. In terms of toxicities, 14 (17%) and 7 (8%) pts had grade (G)1-2 and G3 transaminases secondary to InO, respectively. One pt each had G2 and G3 pancreatitis, respectively. One (1%) and 2 (2%) pts had G2 and G4 veno-occlusive disease secondary to InO, respectively. Two of these pts were treated with defibrotide. Two (2%) pts died due to InO toxicity. A complete description of adverse events are summarized in Table 1. Conclusion: Our real-world data obtained by multicenter collaboration suggest that InO was well tolerated and had significant efficacy in this heavily treated patient population of RR B-cell ALL. Disclosures Liedtke: Celator: Research Funding; Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding; Genentech/Roche: Research Funding; Gilead: Membership on an entity's Board of Directors or advisory committees, Research Funding; IQVIA/Jazz: Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees, Research Funding; Pfizer: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Prothena: Membership on an entity's Board of Directors or advisory committees, Research Funding; Takeda: Membership on an entity's Board of Directors or advisory committees, Research Funding; Caelum: Membership on an entity's Board of Directors or advisory committees; BlueBirdBio: Research Funding; Adaptive: Membership on an entity's Board of Directors or advisory committees; Agios: Research Funding; Amgen/Onyx: Consultancy, Honoraria, Research Funding. Aldoss:Jazz Pharmaceuticals: Honoraria, Other: travel/accommodation/expenses, Speakers Bureau; Agios: Consultancy, Honoraria; AUTO1: Consultancy; Helocyte: Consultancy, Honoraria, Other: travel/accommodation/expenses. Curran:Incyte: Research Funding; Merck: Research Funding; Gilead: Research Funding. Podoltsev:Celgene: Other: Grant funding, Research Funding; Genentech: Research Funding; AI Therapeutics: Research Funding; Agios Pharmaceuticals: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Blueprint Medicines: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Incyte: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Boehringer Ingelheim: Research Funding; Astellas Pharma: Research Funding; Daiichi Sankyo: Research Funding; Sunesis Pharmaceuticals: Research Funding; Jazz Pharmaceuticals: Research Funding; Pfizer: Research Funding; Astex Pharmaceuticals: Research Funding; CTI Biopharma: Research Funding; Samus Therapeutics: Research Funding; Arog Pharmaceuticals: Research Funding; Kartos Therapeutics: Research Funding; Alexion: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Pfizer: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees. Yang:AstraZeneca: Research Funding; Agios: Consultancy. Mattison:Pfizer: Membership on an entity's Board of Directors or advisory committees. Advani:Pfizer: Honoraria, Research Funding; Amgen: Research Funding; Macrogenics: Research Funding; Glycomimetics: Consultancy, Research Funding; Kite Pharmaceuticals: Consultancy; Abbvie: Research Funding. Atallah:Takeda: Consultancy, Research Funding; Jazz: Consultancy; Helsinn: Consultancy; Novartis: Consultancy; Pfizer: Consultancy; Jazz: Consultancy; Helsinn: Consultancy.