Abstract: Standard treatment options in classic HCL (cHCL) result in high response rates and near normal life expectancy. However, the disease itself and the recommended standard treatment are associated with profound and prolonged immunosuppression, increasing susceptibility to infections and the risk for a severe course of COVID-19. The Hairy Cell Leukemia Foundation (HCLF) has recently convened experts and discussed different clinical strategies for the management of these patients. The new recommendations adapt the 2017 consensus for the diagnosis and management with cHCL to the current COVID-19 pandemic. They underline the option of active surveillance in patients with low but stable blood counts, consider the use of targeted and non-immunosuppressive agents as first-line treatment for cHCL, and give recommendations on preventive measures against COVID-19.

Abstract: Hairy cell leukemia is an uncommon hematologic malignancy characterized by pancytopenia and marked susceptibility to infection. Tremendous progress in the management of patients with this disease has resulted in high response rates and improved survival, yet relapse and an appropriate approach to re-treatment present continuing areas for research. The disease and its effective treatment are associated with immunosuppression. Because more patients are being treated with alternative programs, comparison of results will require general agreement on definitions of response, relapse, and methods of determining minimal residual disease. The development of internationally accepted, reproducible criteria is of paramount importance in evaluating and comparing clinical trials to provide optimal care. Despite the success achieved in managing these patients, continued participation in available clinical trials in the first-line and particularly in the relapse setting is highly recommended. The Hairy Cell Leukemia Foundation convened an international conference to provide common definitions and structure to guide current management. There is substantial opportunity for continued research in this disease. In addition to the importance of optimizing the prevention and management of the serious risk of infection, organized evaluations of minimal residual disease and treatment at relapse offer ample opportunities for clinical research. Finally, a scholarly evaluation of quality of life in the increasing number of survivors of this now manageable chronic illness merits further study. The development of consensus guidelines for this disease offers a framework for continued enhancement of the outcome for patients.

Abstract: Rare, recurrent balanced translocations occur in a variety of cancers but are often not functionally interrogated. Balanced translocations with the immunoglobulin heavy chain locus ( IGH ; 14q32) in chronic lymphocytic leukemia (CLL) are infrequent but have led to the discovery of pathogenic genes including CCND1 , BCL2 , and BCL3 . Following identification of a t(X;14)(q28;q32) translocation that placed the mature T cell proliferation 1 gene ( MTCP1 ) adjacent to the immunoglobulin locus in a CLL patient, we hypothesized that this gene may have previously unrecognized importance. Indeed, here we report overexpression of human MTCP1 restricted to the B cell compartment in mice produces a clonal CD5 + /CD19 + leukemia recapitulating the major characteristics of human CLL and demonstrates favorable response to therapeutic intervention with ibrutinib. We reinforce the importance of genetic interrogation of rare, recurrent balanced translocations to identify cancer driving genes via the story of MTCP1 as a contributor to CLL pathogenesis.

Abstract: Chronic lymphocytic leukemia (CLL) is the most prevalent adult leukemia in Western countries and is spelled by substantial genetic and clinical heterogeneity. During CLL transformation, loss or gain of genetic material appears to be a key determinant of disease phenotype and clinical outcome, with major chromosome aberrations observed in up to 80% of patients. Alternatively, balanced translocations, specifically those resulting in constitutive over-expression of various proto-oncogenes under the immunoglobulin heavy chain locus (IGH; 14q32), occur far less frequently. Despite their infrequence, molecular profiling of these rare rearrangements have revealed broad importance of un-recognized genes critical to the pathogenesis of CLL. Employing this strategy, we identified a young CLL patient with a previously undescribed t(X;14)(q28;q32) translocation, co-localization of the mature T cell proliferation 1 (MTCP1; Xq28) coding region with the IGH locus, triggering overexpression of MTCP1 in the CLL cells. Translocations involving MTCP1 are a driving factor in T-prolymphocytic leukemia; however, a role for MTCP1 in CLL has not been described. Inspired by this observation, we screened & gt;1700 suspected CLL cases and evaluated gene expression data for further evidence of MCTP1 aberrations. This query identified seven additional Xq28 rearrangements, revealed MTCP1 mRNA was globally over-expressed in CLL cells compared to normal B-cells, and increased MTCP1 mRNA expression portends a poor response to chemoimmunotherapy. To establish a role for MTCP1 as an oncogene in B cell malignancies, we generated a mouse model with B cell-specific MTCP1 overexpression (Eµ-MTCP1). Longitudinal evaluation revealed a majority of Eµ-MTCP1 mice developed a lethal hematologic malignancy between 5-12 months of age, highlighted by the progressive emergence of clonally related CLL-like B lymphocytes (CD19+/CD5+ B cells) in the blood and accumulating in the spleen and lymph nodes. To support the use of the newly generated Eµ-MTCP1 mouse as a tool for pre-clinical evaluation of CLL therapeutics, we demonstrate that continuous ibrutinib administration in Eµ-MTCP1 mice was sufficient to delay the onset of the CLL-like disease and significantly prolonged survival. In summary, we report Xq28 translocations as rare genetic abnormalities in CLL, yet being one mechanism by which CLL cells amplify expression of MTCP1 compared to normal B cell subsets. Further, the Eµ-MTCP1 mouse model should be considered as an alternative tool for both biologic assessment of co-expressed genes and pre-clinical evaluation of novel CLL therapeutics. Lastly, relevant to all cancer types, successful application of a strategy pursuing the functional consequence of genes involved in rare translocations contributed to the understanding of this disease and identified a novel target for future therapeutic consideration. Citation Format: Janek S. Walker, Zachary A. Hing, Steven Sher, James Cronin, Katie Williams, Bonnie Harrington, Jordan N. Skinner, Casey B. Cempre, Charles T. Gregory, Max Yano, Larry P. Beaver, Brandi R. Walker, Jadwiga M. Labanowska, Nyla A. Heerema, Krzysztof Mrozek, Jennifer A. Woyach, Amy S. Ruppert, Amy Lehman, Hatice Gulcin Ozer, Vincenzo Coppola, John C. Byrd, James S. Blachly, Rosa Lapalombella. Evaluating a rare t(X;14)(q28;q32) translocation reveals MTCP1 as a driving factor in chronic lymphocytic leukemia [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 2260.

Abstract: BACKGROUND: The study of rare diseases is limited by the uncommon nature of the conditions as well as the widely dispersed patient populations. Current rare disease registries such as the National Organization of Rare Diseases utilize centralized platforms for data collection; however because of their broad nature, these do not always capture unique, disease specific elements. Hairy Cell Leukemia (HCL) is a rare leukemia globally with approximately 900 new cases diagnosed in the US each year. The HCL Foundation undertook creation of a Patient Data Registry that collects data from multiple HCL Centers of Excellence (COE) around the globe to better understand the complications, treatment outcomes, disease subtypes, comorbid conditions, epidemiology, and quality of life of patients with HCL. METHODS: Investigators at The Ohio State University Department of Biomedical Informatics and Division of Hematology in collaboration with the HCL Foundation developed a Patient Data Registry (PDR) for the longitudinal capture of high quality research data. This system differs from other registries in that it uses a federated( rather than centralized) architecture, wherein data is queried and integrated in an on-demand manner from local registry databases at each participating site. Further, the data collected for use in the registry combines both automated exports from existing electronic health records (EHRs) as well as additional data entered via a set of web-based forms. All manually entered data comes from source documents, and data provenance spanning electronic and manually entered data is maintained via multiple technical measures. Patients may be enrolled at HCL COE, or, if they do not have access to a COE they may enroll via a web-based portal (www.hairycellleukemia.org). At this time due to regulatory requirements the web-based portal is available to US patients only. All data are de-identified (see Figure 1: De-Identification Workflow) which reduces regulatory burden and increases opportunities for data access and re-use. End users have access to data via a project-specific query portal. RESULTS: The Patient Data Registry has been deployed at The Ohio State University, Royal Marsden Hospital, and MD Anderson Cancer Center, and is undergoing deployment at the University of Rochester. Up to 25 international HCL COE may participate. In addition, US patients are actively entering the registry via the web-based portal. To date, 227 patients have been consented to the registry with 119 of these being via the web-based entry point. CONCLUSION: We created an international and web-based patient data registry which will enable researchers to study outcomes in HCL in ways not previously possible given the rarity of the disease. This work was made possible by research funding from the Hairy Cell Leukemia Foundation. Figure De-Identification Workflow Figure. De-Identification Workflow Disclosures Andritsos: Hairy Cell Leukemia Foundation: Research Funding. Anghelina:Hairy Cell Leukemia Foundation: Research Funding. Lele:Hairy Cell Leukemia Foundation: Research Funding. Burger:Pharmacyclics: Research Funding. Delgado:Gilead: Consultancy, Honoraria; Novartis/GSK: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; Roche: Consultancy, Honoraria, Research Funding; Infinity: Research Funding. Jones:AbbVie: Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen: Membership on an entity's Board of Directors or advisory committees, Research Funding; Pharmacyclics, LLC, an AbbVie Company: Membership on an entity's Board of Directors or advisory committees, Research Funding. Lozanski:Beckman Coulter: Research Funding; Genentech: Research Funding; Stemline Therapeutics Inc.: Research Funding; Boehringer Ingelheim: Research Funding. Montserrat:Morphosys: Other: Expert Testimony; Vivia Biotech: Equity Ownership; Gilead: Consultancy, Other: Expert Testimony; Pharmacyclics: Consultancy; Janssen: Honoraria, Other: travel, accommodations, expenses. Parikh:Pharmacyclics: Honoraria, Research Funding. Park:Genentech/Roche: Research Funding; Amgen: Consultancy; Juno Therapeutics: Consultancy, Research Funding. Robak:Pharmacyclics, LLC, an AbbVie Company: Consultancy, Honoraria, Research Funding; Janssen: Consultancy, Honoraria, Research Funding; AbbVie: Consultancy, Honoraria, Research Funding. Tam:janssen: Honoraria, Research Funding; Roche: Honoraria, Membership on an entity's Board of Directors or advisory committees; AbbVie: Honoraria, Membership on an entity's Board of Directors or advisory committees. Heckler:Hairy Cell Leukemia Foundation: Research Funding. Payne:Hairy Cell Leukemia Foundation: Research Funding.

Abstract: A significant body of literature has been generated related to the detection of measurable residual disease (MRD) at the time of achieving complete remission (CR) in patients with hairy cell leukemia (HCL). However, due to the indolent nature of the disease as well as reports suggesting long-term survival in patients treated with a single course of a nucleoside analog albeit without evidence of cure, the merits of detection of MRD and attempts to eradicate it have been debated. Studies utilizing novel strategies in the relapse setting have demonstrated the utility of achieving CR with undetectable MRD (uMRD) in prolonging the duration of remission. Several assays including immunohistochemical analysis of bone marrow specimens, multi-parameter flow cytometry and molecular assays to detect the mutant BRAF V600E gene or the consensus primer for the immunoglobulin heavy chain gene ( IGH ) rearrangement have been utilized with few comparative studies. Here we provide a consensus report on the available data, the potential merits of MRD assessment in the front-line and relapse settings and recommendations on future role of MRD assessment in HCL.

Abstract: Hairy cell leukemia (HCL) is a rare B-cell malignancy, and there is a need for novel treatments for patients who do not benefit from purine analogs. Ibrutinib, an oral agent targeting Bruton tyrosine kinase in the B-cell receptor signaling pathway, is highly effective in several malignancies. Its activity in HCL was unknown, so we conducted a multisite phase 2 study of oral ibrutinib in patients with either relapsed classic or variant hairy cell leukemia. The primary outcome measure was the overall response rate (ORR) at 32 weeks, and we also assessed response at 48 weeks and best response during treatment. Key secondary objectives were characterization of toxicity and determination of progression-free survival (PFS) and overall survival (OS). Thirty-seven patients were enrolled at 2 different doses (24 at 420 mg, 13 at 840 mg). The median duration of follow-up was 3.5 years (range, 0-5.9 years). The ORR at 32 weeks was 24%, which increased to 36% at 48 weeks. The best ORR was 54%. The estimated 36-month PFS was 73% and OS was 85%. The most frequent adverse events were diarrhea (59%), fatigue (54%), myalgia (54%), and nausea (51%). Hematologic adverse events were common: anemia (43%), thrombocytopenia (41%), and neutropenia (35%). Ibrutinib can be safely administered to patients with HCL with objective responses and results in prolonged disease control. Although the initial primary outcome objective of the study was not met, the observation of objective responses in heavily pretreated patients coupled with a favorable PFS suggests that ibrutinib may be beneficial in these patients. This trial was registered at www.clinicaltrials.gov as #NCT01841723.

Abstract: Background: AML is a highly aggressive hematologic malignancy. Patient (pt) outcomes are affected by disease-related factors including cytogenetic findings and gene mutations, as well as pt-related factors, such as age and race. Younger pts have superior survival: ~50% of pts diagnosed as AYAs (18-39 years) may be cured of their disease. However, the impact of race on the outcome and associated disease profiles in this pt population are unknown. Methods: We compared survival and molecular profiles of 655 Non-Hispanic Black and Non-Hispanic White (hereafter referred to as Black, n=89 and White, n=566) AYA AML pts treated on frontline Cancer and Leukemia Group B/Alliance for Clinical Trials in Oncology protocols based on standard intensity cytarabine/anthracycline induction therapy between 1986 and 2016. Three hundred ten pts were analyzed molecularly via targeted sequencing of 81 genes. Additionally, we performed integrated genomic profiling (whole-exome sequencing and transcriptome sequencing) and measured residual disease (MRD) in serial samples of 4 Black pts who relapsed with their disease. Results: A comparison of clinical characteristics of AYA AML pts by race revealed almost identical age and sex distribution, and we found no significant differences between clinical features at diagnosis. With regard to genetic profiles, 42% of White pts were cytogenetically normal, whereas only 18% of Black pts had cytogenetically normal AML (CN-AML; p & lt;0.001). The abnormal karyotypes in Black pts more often contained abnormalities associated with core-binding factor (CBF) AML (39% v 25%, p=0.01; Fig. 1A). White pts had more known pathogenic NPM1 variants (29% v 9%, p=0.01), whereas Black pts had a higher incidence of ZRSR2 pathogenic variants (9% v 0.4%, p=0.004) and tended to have pathogenic KRAS variants more often (12% v 5%, p=0.11; Fig. 1B). Black AYA AML pts had worse outcomes including a higher early death rate (ED, defined as death within 30 days of diagnosis; 11% v 2%, p & lt;0.001), a trend towards lower complete remission (CR) rate (73% v 82%, p=0.06) and a shorter overall survival (OS; median, 1.5 v 3.1 years [y], p=0.002). Notably, this survival disparity was almost exclusively driven by pts aged 18-29 y: Black pts had a higher ED rate (16% v 3%, p=0.002), a lower CR rate (66% v 83%, p=0.01) and shorter OS (median, 1.3 v 10.2 y, p & lt;0.001) but not disease-free survival (DFS; p=0.16) than White pts aged 18-29 y. In contrast, there were no significant differences in these outcome metrics between Black and White pts aged 30-39 y (Fig. 2). Among all pts consolidated with intensive chemotherapy (n=566), multivariable analysis revealed Black race as an independent prognosticator of shorter DFS (p=0.04) and OS (p & lt;0.001). These differences in OS were also significant when we included pts who received allogeneic transplantation in 1st CR (n=655; p & lt;0.001). 18-29 y old Black pts with any non-CBF AML had very poor OS compared to White pts (5-y rates, 12% v 45%, p & lt;0.001). CBF-AML pts aged 18-29 y tended to have an inferior OS compared with White pts (5-y rates, 41% v 44%, p=0.10). To gain insights into the genetic features of Black AYA AML pts at different stages of the disease, we performed integrated genomic profiling on paired leukemic samples from diagnosis and relapse of 4 Black AYA pts. In all pts, the original dominant leukemic clone persisted and was dominant at relapse (Fig. 3). This suggests that the leukemic clone persists during treatment with conventional cytotoxic chemotherapy. This observation was further supported by MRD detection of NPM1 mutations in NPM1-mutated pts at time of morphologic CR. Conclusion: Black AYA AML pts present with distinct molecular features, including very high frequencies of CBF AML, and low frequency of NPM1. Pts aged 18-29y account for the race-associated survival disparity, especially non-CBF pts who have dramatically poor survival. On the one hand, the lower CR rates combined with persistence of dominant clones at relapse suggest reduced response to induction chemotherapy, and suggests the need for different treatment intensities and/or modalities in this pt cohort. On the other hand, high early death rates are indicative of delay in diagnosis and care, including health inequities, calling for systematic changes particularly for this population. Figure 1 Figure 1. Disclosures Blachly: KITE: Consultancy, Honoraria; INNATE: Consultancy, Honoraria; AbbVie: Consultancy, Honoraria; AstraZeneca: Consultancy, Honoraria. Mims: Leukemia and Lymphoma Society's Beat AML clinical study: Consultancy, Research Funding; Aptevo: Research Funding; Daiichi Sankyo: Consultancy, Research Funding; Glycomemetics: Research Funding; Kartos Pharmaceuticals: Research Funding; Xencor: Research Funding; Genentech: Consultancy; Abbvie: Consultancy; BMS: Consultancy; Kura Oncology: Consultancy; Syndax Pharmaceuticals: Consultancy; BMS: Consultancy; Jazz Pharmaceuticals: Consultancy; Aptevo: Research Funding. Walker: Karyopharm Therapeutics: Current Employment, Current holder of individual stocks in a privately-held company, Current holder of stock options in a privately-held company. Blum: Leukemia and Lymphoma Society: Research Funding; Syndax: Honoraria; AmerisourceBergen: Honoraria; Abbvie: Honoraria; Celyad Oncology: Research Funding; Nkarta: Research Funding; Forma Therapeutics: Research Funding; Xencor: Research Funding. Larson: Rafael Pharmaceuticals: Research Funding; Epizyme: Consultancy; Astellas: Consultancy, Research Funding; Gilead: Research Funding; CVS/Caremark: Consultancy; Takeda: Research Funding; Novartis: Research Funding; Cellectis: Research Funding. Stone: Onconova: Consultancy; Boston Pharmaceuticals: Consultancy; Innate: Consultancy; Jazz: Consultancy; Novartis: Consultancy, Research Funding; AbbVie: Consultancy; GlaxoSmithKline: Consultancy; Gemoab: Membership on an entity's Board of Directors or advisory committees; Foghorn Therapeutics: Consultancy; Janssen: Consultancy; Arog: Consultancy, Research Funding; Aprea: Consultancy; Elevate Bio: Membership on an entity's Board of Directors or advisory committees; Bristol Myers Squibb: Consultancy; BerGen Bio: Membership on an entity's Board of Directors or advisory committees; Astellas: Membership on an entity's Board of Directors or advisory committees; Amgen: Membership on an entity's Board of Directors or advisory committees; Actinium: Membership on an entity's Board of Directors or advisory committees; Syndax: Membership on an entity's Board of Directors or advisory committees; Celgene: Consultancy; Syntrix/ACI: Membership on an entity's Board of Directors or advisory committees; Syros: Membership on an entity's Board of Directors or advisory committees; Takeda: Consultancy; Agios: Consultancy, Research Funding; Macrogenics: Consultancy. Paskett: Pfizer: Research Funding; Merck: Research Funding. Byrd: 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; Novartis, Trillium, Astellas, AstraZeneca, Pharmacyclics, Syndax: Consultancy, Honoraria. Eisfeld: Karyopharm (spouse): Current Employment.

Abstract: Background: AML is a clinically and molecularly heterogeneous disease associated with poor survival. Multiple disease-related factors including cytogenetic findings and gene mutations, as well as patient-related factors, such as demographics and African American (AA) heritage, have been identified that impact on pt outcomes. However, with recent improved survival it is unknown whether racial health disparities persist. Moreover, we are not aware of a large study that assessed possible race-associated molecular differences. Thus, the goals of our study were to 1) analyze the outcomes of adult AML pts in a nationwide population study, including possible impacts of sociodemographic, financial and racial disparities and 2) characterize molecular features of AA compared with those of Caucasian AML pts. Methods: For a nationwide population analysis, the Surveillance Epidemiology End Results (SEER) Program of the National Cancer Institute was used to identify 11,190 adults aged 18-60 years (y) diagnosed with AML (excluding acute promyelocytic leukemia) between 1986 and 2015. To characterize molecular features we performed targeted sequencing of 81 genes in 1,339 AML pts treated on frontline Cancer and Leukemia Group B/Alliance for Clinical Trials in Oncology (Alliance) protocols based on standard intensity cytarabine/anthracycline induction followed by consolidation between 1986 and 2016. No Alliance pt received an allogeneic stem cell transplant in 1st complete remission (CR). Results: The associations between demographic parameters and risk of death among SEER registry AML pts are shown in Table 1. While there was a slightly higher risk of death for men (HR 1.09) and a lower risk of death for pts with a higher median household income ( & gt;79.6k vs & lt;54.4k, HR 0.85), the strongest factor affecting survival of AML pts was self-reported pt race, after accounting for other variables in the model. Specifically, AA AML pts had a higher risk of death compared with that of white AML pts (HR 1.28), with 3-year (y) overall survival (OS) rates of 32% and 41%, respectively (P & lt;.001; Figure 1A). To evaluate if this race-associated survival disparity also persists in pts treated in the setting of clinical trials, we analyzed the survival of pts similarly treated on Alliance protocols. Although there was no difference in CR rates between AA and Caucasian Alliance AML pts, AA pts had inferior disease-free survival (DFS; median, 0.8 y vs 1.4 y, P=.02) and OS (median, 1.2 y vs 1.8 y, P=.02) compared with Caucasian pts, indicating that access to similar treatments might not alleviate racial survival disparities (Figure 1B). To assess whether any race-associated pretreatment features may help explain the different outcomes, we analyzed the clinical, cytogenetic and gene mutation features of the Alliance cohort. AA pts less often had normal cytogenetics (38% vs 51%, P=.01) and had a lower frequency of prognostically favorable NPM1 mutations (25% vs 38%, P=.04) and higher frequencies of spliceosome gene mutations (24% vs 12%; P=.009) than Caucasian pts. Multivariable analyses for outcome in AA pts did not identify any molecular features associated with achievement of CR or DFS. However, AA pts harboring FLT3-ITD or IDH2 mutations had shorter OS compared with wild-type pts (FLT3-ITD, HR=1.95, P=.03; IDH2, HR=2.17, P=.008). Notably, other well-established mutational features known to associate with outcome (e.g., NPM1 or TP53 mutations) did not impact on survival. Lastly, we performed uni- and multivariable outcome analyses for OS in our Alliance pts. Remarkably, being NPM1-mutated and not being AA were the only positive prognostic factors associated with longer OS in the final risk model (NPM1 mut vs wt, HR=0.72, P & lt;.001; Caucasian vs AA, HR=0.72, P=.03). Conclusion: Self-reported AA race is the most important pt-associated factor associated with poor survival in AML pts & lt; 60 y of age based on SEER. Survival analyses in Alliance pts identify AA race as independent poor survival prognosticator in AML pts besides established molecular markers. . This disparity must be urgently addressed to ensure improved outcomes for AA AML pts, and larger studies to establish molecular risk profiles are needed. Support: U10CA180821, U10CA180882 U24CA196171, https://acknowledgments.alliancefound.org; Clinicaltrials.gov Identifiers: NCT00048958, NCT00899223, NCT00900224 Disclosures Bhatnagar: KaryoPharm Therapuetics: Research Funding; Cell Therapeutics: Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Membership on an entity's Board of Directors or advisory committees; Astellas: Membership on an entity's Board of Directors or advisory committees; Pfizer: Membership on an entity's Board of Directors or advisory committees; KITE: Membership on an entity's Board of Directors or advisory committees. Blachly:AbbVie, AstraZeneca, KITE Pharma: Consultancy. Mims:Novartis: Speakers Bureau; Jazz Pharmaceuticals: Other: Data Safety Monitoring Board; Syndax Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees; Abbvie: Membership on an entity's Board of Directors or advisory committees; Kura Oncology: Membership on an entity's Board of Directors or advisory committees; Leukemia and Lymphoma Society: Other: Senior Medical Director for Beat AML Study; Agios: Consultancy. Walker:Vigeo Therapeutics: Consultancy; Karyopharm: Current Employment, Current equity holder in publicly-traded company. Powell:Genentech: Research Funding; Jazz Pharmaceuticals: Consultancy, Other: Advisor, Research Funding; Pfizer: Research Funding; Rafael Pharmaceuticals: Consultancy, Other: Advisor, Research Funding; Novartis: Research Funding. Kolitz:Magellan: Membership on an entity's Board of Directors or advisory committees; Pfizer: Membership on an entity's Board of Directors or advisory committees. Stone:Biolinerx: Consultancy; Novartis: Consultancy, Research Funding; Celgene: Consultancy, Other; Aztra-Zeneca: Consultancy; Jazz: Consultancy; Argenix: Other; Janssen: Consultancy; Daiichi-Sankyo: Consultancy; Pfizer: Consultancy; Gemoab: Consultancy; Syndax: Consultancy, Research Funding; Takeda: Other: DSMB; Macrogenics: Consultancy; Trovagene: Consultancy; Syntrix: Other: DSMB; Abbvie: Consultancy, Research Funding; Agios: Consultancy, Research Funding; Actinium: Consultancy, Membership on an entity's Board of Directors or advisory committees; Astellas: Consultancy; Arog: Consultancy, Research Funding; Syros: Consultancy; Stemline: Consultancy. Byrd:Trillium: Research Funding; Leukemia and Lymphoma Society: Other; Acerta Pharma: Research Funding; Syndax: Research Funding; Pharmacyclics LLC, an AbbVie Company, Janssen, Novartis, Gilead, TG Therapeutics: Other; Janssen: Consultancy; Pharmacyclics LLC, an AbbVie Company, Gilead, TG Therapeutics, BeiGene: Research Funding; Pharmacyclics LLC, an AbbVie Company, Gilead, TG Therapeutics, Novartis, Janssen: Speakers Bureau; Kartos Therapeutics: Research Funding; Vincera: Research Funding; Novartis: Research Funding. Eisfeld:Karyopharm: Current Employment, Current equity holder in publicly-traded company; Vigeo Therapeutics: Consultancy.