Citations

AbstractIntroductionHyperthermic intraperitoneal chemotherapy (HIPEC) during cytoreductive surgery (CRS) is typically reserved for a complete or optimal cytoreduction. There is the potential for therapeutic effect of HIPEC with an incomplete cytoreduction, particularly for near optimal cytoreductions.MethodsRetrospective review of incomplete cytoreductions (R2b, R2c) for appendiceal and colorectal primaries. Primary endpoints were overall survival (OS) and progression‐free survival (PFS). Subgroup analysis for primary etiology and specific cytoreductive score.ResultsA total of 121 cases of incomplete CRS, 74 CRS alone, and 47 CRS‐HIPEC. For the entire study group there was a survival benefit with HIPEC. OS and PFS were 2.3 versus 1.4 (p = 0.001) and 1.6 versus 0.7 (p < 0.0001) respectively for cases with and without HIPEC. Subgroup analysis of appendiceal neoplasms, 43 CRS‐HIPEC and 50 CRS alone, found HIPEC benefit persisted; OS and PFS were 2.4 versus 1.5 (p = 0.016) and 1.7 versus 0.8 (p < 0.0001), respectively for cases with and without HIPEC. Benefit most pronounced in low‐grade cases with doubling of the OS and PFS (p = 0.004). With colorectal primary cases, 10 CRS‐HIPEC and 18 CRS alone, no difference in OS and PFS. When stratifying out by cytoreduction scores, R2b and R2c, HIPEC only provided a benefit for R2b cases; OS and PFS for R2b cases were 2.28 versus 1.01 (p = 0.011) and 1.67 versus 0.75 (p = 0.001), respectively for cases with and without HIPEC.ConclusionHIPEC has utility for incomplete cytoreductions with appendiceal neoplasms, greatest effect with low‐grade appendiceal neoplasms. HIPEC is only beneficial for near optimal cytoreductions (R2b).

The NCCN Guidelines for Hepatobiliary Cancers focus on the screening, diagnosis, staging, treatment, and management of hepatocellular carcinoma (HCC), gallbladder cancer, and cancer of the bile ducts (intrahepatic and extrahepatic cholangiocarcinoma). Due to the multiple modalities that can be used to treat the disease and the complications that can arise from comorbid liver dysfunction, a multidisciplinary evaluation is essential for determining an optimal treatment strategy. A multidisciplinary team should include hepatologists, diagnostic radiologists, interventional radiologists, surgeons, medical oncologists, and pathologists with hepatobiliary cancer expertise. In addition to surgery, transplant, and intra-arterial therapies, there have been great advances in the systemic treatment of HCC. Until recently, sorafenib was the only systemic therapy option for patients with advanced HCC. In 2020, the combination of atezolizumab and bevacizumab became the first regimen to show superior survival to sorafenib, gaining it FDA approval as a new frontline standard regimen for unresectable or metastatic HCC. This article discusses the NCCN Guidelines recommendations for HCC.

Abstract Introduction: Allogeneic stem cell transplantation (alloSCT) is the most effective post remission anti-leukemia strategy. However, the associated toxicity is a barrier for its routine adoption as standard of care in older adults. Studies of AML patients who underwent alloSCT are mainly retrospective as randomized controlled trials comparing transplantation to non-transplantation are very difficult to conduct. We herein present prospective data from a randomized controlled phase III study, E2906, designed to compare two intensive chemotherapy arms. Patients who achieved remission and had a donor were to proceed to alloSCT after induction or first consolidation, at investigator discretion. Non-transplanted patients received 2 cycles of consolidation and then underwent a second randomization between observation and decitabine maintenance. Herein are reported all patients who received alloSCT either on protocol during first remission (CR1) or at other post induction time-points. Patients and Methods: Enrolled to E2906 study were 727 AML patients age 60 years and over. AlloSCT was performed in 166 patients, of whom 71 received alloSCT as part of the study and 95 received alloSCT off protocol. 105 patients (66/71 on protocol, 39/95 off protocol) received alloSCT at CR1/CRi1/LFS1 (CR: 92, CRi: 9 LFS: 4). Patients were followed for a median of 33.6 months from diagnosis and 29.1 months from transplant. No patients received decitabine maintenance prior to alloSCT. Overall survival (OS) is defined as the time from allo transplant to death from any cause, with follow-up censored at the date of last contact. Disease free survival (DFS) is defined as the time from alloSCT transplant to relapse or death of any cause. The censored follow-up time for patients without relapse or death information is the date of last contact. Kaplan-Meier estimates were used to estimate OS and DFS. DFS and OS were compared between subgroups using log rank tests. A cumulative incidence analysis, with death without prior relapse as competing events, was performed to evaluate the subgroup effect on time to relapse after transplant. Results: Patient characteristics of those who received alloSCT at CR1/CRi1/LFS1 are similar to the general distribution of AML patients eligible for intensive chemotherapy. Median age was 66 years, 52% were male and 88% with ECOG PS of 0-1. Cytogenetic data were available for 85 patients of whom 26% presented with unfavorable cytogenetics. Minimal residual disease (MRD) status prior to alloSCT was available for 44 patients of whom 19 (43%) achieved a MRD negative state. Long-term OS and DFS rates for all 105 patients who underwent alloSCT at CR1/CRi1/LFS1 are encouraging (Figure 1). OS and DFS at two years were 56.4% and 53.6% and 49.4%, 45.6% and 42.9%, 39% at 3 and 4 years, respectively. Age above or below 65 years, gender, induction regimen (3+7 or clofarabine) and MRD status prior to transplantation had no impact on outcome. Survival curves by intermediate or adverse cytogenetic risk are not significantly different. The numbers of patients with CRi1 or LFS1 are too small to compare with patients in CR1. Nevertheless, 36/38 patients that were alive and remain in first remission at the time of data cutoff, are patients who achieved CR1 and only 2/38 are patients transplanted at CRi1 or LFS1. Notably, the non-relapse mortality (NRM) was not significantly different for patients less or over 65 years. NRM at 6 months and 2 years for patients over and under 65 years of age were 4.4%, 8.4% and 15.6%, 24.0% respectively. Relapse during the first year post alloSCT is the main barrier for longer survival, particularly in patients with adverse cytogenetics and MRD positivity prior to transplantation (Figure 2). Conclusions: Fit older patients, including those over age 65, who undergo an alloSCT in CR1, can expect a 4-year survival of 43% with an acceptable NRM rate. The NRM was, surprisingly, not higher than for a typically younger cohort of AML. Relapse within one year after transplant is the major limitation to prolonged survival and this finding reflects the biology of the leukemia in these patients. In this patient population, novel post remission strategies should either be complimentary to alloSCT or competitive with updated outcome of alloSCT. Figure 1 Figure 1. Disclosures Ofran: Medison Israel: Consultancy; Janssen: Consultancy; Pfizer: Consultancy; Astellas: Consultancy; AbbVie: Consultancy. Claxton: Astellas: Other: Clinical Trial; Novartis: Research Funding; Astex: Research Funding; Cyclacel: Research Funding; Daiichi Sankyo: Research Funding; Incyte: Research Funding. Tallman: Syros: Membership on an entity's Board of Directors or advisory committees; Kura: Membership on an entity's Board of Directors or advisory committees; NYU Grand Rounds: Honoraria; 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. Melnick: Constellation: Consultancy; Epizyme: Consultancy; Daiichi Sankyo: Research Funding; Sanofi: Research Funding; Janssen Pharmaceuticals: Research Funding; KDAC Pharma: Membership on an entity's Board of Directors or advisory committees. Levine: Prelude: Membership on an entity's Board of Directors or advisory committees; Ajax: Membership on an entity's Board of Directors or advisory committees; Zentalis: Membership on an entity's Board of Directors or advisory committees; Mission Bio: Membership on an entity's Board of Directors or advisory committees; QIAGEN: Membership on an entity's Board of Directors or advisory committees; Gilead: Honoraria; Lilly: Honoraria; Morphosys: Consultancy; Janssen: Consultancy; Incyte: Consultancy; Astellas: Consultancy; Imago: Membership on an entity's Board of Directors or advisory committees; Auron: Membership on an entity's Board of Directors or advisory committees; Amgen: Honoraria; Celgene: Research Funding; Roche: Honoraria, Research Funding; 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. Lazarus: Bristol Myer Squibb: Membership on an entity's Board of Directors or advisory committees. 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. Foran: gamida: Honoraria; aptose: Research Funding; syros: Honoraria; boehringer ingelheim: Research Funding; kura: Research Funding; takeda: Research Funding; abbvie: Research Funding; trillium: Research Funding; revolution medicine: Honoraria; certara: Honoraria; actinium: Research Funding; OncLive: Honoraria; pfizer: Honoraria; servier: Honoraria; bms: Honoraria; novartis: Honoraria; taiho: Honoraria; sanofi aventis: Honoraria; h3bioscience: Research Funding; aprea: Research Funding; sellas: Research Funding; stemline: Research Funding. Litzow: Jazz: Other: Advisory Board; AbbVie: Research Funding; Omeros: Other: Advisory Board; Amgen: Research Funding; Actinium: Research Funding; Astellas: Research Funding; Pluristem: Research Funding; Biosight: Other: Data monitoring committee.

Abstract Introduction: The gut microbiome is a potentially modifiable factor in treatment related outcomes in allogeneic hematopoietic cell transplant (HCT). Prior studies have linked pre- or mid-treatment gut microbiome diversity with risk for treatment related morbidity and mortality. However, these studies have been limited by the inclusion of one or only a few institutions and the lack of longitudinal sampling with high quality metadata. These limitations complicate the interpretation of microbiome alterations over the course of HCT. Methods: To overcome these, we devised and implemented a large-scale biospecimen collection protocol in conjunction with BMT CTN 1703, a randomized, multicenter, Phase III trial of tacrolimus/methotrexate vs. post-transplant cyclophosphamide/tacrolimus/mycophenolate mofetil in reduced intensity conditioning (RIC) allogeneic HCT (NCT03959241). Patients enrolled on 1703 were optionally co-enrolled in the companion immune and microbiome profiling study, 1801 (MI-IMMUNE). This involved blood, urine and stool sampling before conditioning (PCON), then weekly starting on day 0 through day 77 (through day 84 for blood), and on days 98, 180, 270, 365 and 730. For all enrolled participants where the donor consented, residual donor cells were saved from the empty hematopoietic stem cell product bag for later analysis. Additionally, the protocol included one-time blood, urine and stool sample collection from consented matched related donors (MRDs) prior to stem cell collection. Starting with protocol version 4.0 on February 1, 2021, participation in 1801 stool collection was required for the first six out of eighteen sample collection timepoints. Participation in later stool and urine timepoint collections remained optional. Here we review the feasibility of creating a multi-institutional biobank. Additionally, we assess the success of our strategies by calculating sample collection compliance and standard deviation in compliance across centers for each timepoint. Results: On June 18, 2021, BMT CTN 1703/1801 closed to accrual with 431 patients enrolled on 1703; 323 patients from 36 centers were co-enrolled on 1801. 304 (94%) provided study samples, making this the largest prospective microbiome and immune profiling study in HCT patients to date. As of July 6, 2021, 3,683 blood, 2,668 urine, and 2,098 stool samples had been collected. Across the first 6 timepoints for all participating centers, blood, urine and stool sample collection averaged 93%, 82%, and 74% compliance, respectively. Of the 99 (30%) patients enrolled on 1801 with a MRD, 34 (34%) donors consented to sample collection. Sample collection compliance was lower for MRDs than for patients on the study with 76%, 74%, and 62% of expected blood, urine and stool samples collected, respectively, from this group. For stool collection exclusively, a median of 5 samples were collected per patient across the first 6 timepoints (median of 6 across all timepoints) with 93 (31%) of patients completing a full sample set through Day 28. 139 (46%) patients provided at least one sample after day 28; these represented 37% of the total samples collected to date. The PCON sample, which provides an important measure of pre-treatment gut microbiome diversity, had the third highest compliance with 74% of patients providing a sample. Surprisingly, Day 28 had the lowest compliance (66%) and highest standard deviation (37%) possibly because this timepoint often falls around the time of hospital discharge. Between PCON and day 28, the standard deviation between sites in the average collection compliance (24%) and number of samples collected per patient (1.1) was small indicating the successful adoption of stool collection across institutions. Table 1 summarizes sample collection statistics. Conclusion: Overall this study has resulted in a large, novel biobank of blood, urine and stool samples from patients undergoing RIC allogeneic HCT at 36 centers across the US. This will serve as a valuable resource for investigating the role of the gut microbiome in long term health outcomes following HCT. Although the results of 1801 are forthcoming given ongoing sample collection, the size and composition of the biobank to date clearly demonstrate the feasibility of implementing multi-institutional stool collection. This study represents a critical step towards the large-scale adoption of microbiome sampling as a diagnostic tool. Figure 1 Figure 1. Disclosures Chhabra: GSK: Honoraria. Clark: Kadmon: Consultancy. Horowitz: Mesoblast: Research Funding; Shire: Research Funding; Vertex: Research Funding; Stemcyte: Research Funding; Vor Biopharma: Research Funding; Janssen: Research Funding; Miltenyi Biotech: Research Funding; Kiadis: Research Funding; Sobi: Research Funding; Kite/Gilead: Research Funding; Pfizer, Inc: Research Funding; Jazz Pharmaceuticals: Research Funding; Magenta: Consultancy, Research Funding; Medac: Research Funding; Novartis: Research Funding; GlaxoSmithKline: Research Funding; Daiicho Sankyo: Research Funding; Xenikos: Research Funding; Omeros: Research Funding; Orca Biosystems: Research Funding; Pharmacyclics: Research Funding; Regeneron: Research Funding; Tscan: Research Funding; Takeda: Research Funding; CSL Behring: Research Funding; Genentech: Research Funding; Gamida Cell: Research Funding; Chimerix: Research Funding; Bristol-Myers Squibb: Research Funding; bluebird bio: Research Funding; Astellas: Research Funding; Amgen: Research Funding; Allovir: Consultancy; Actinium: Research Funding; Sanofi: Research Funding; Seattle Genetics: Research Funding. Jenq: Microbiome DX: Consultancy; Merck: Consultancy; Prolacta: Consultancy, Membership on an entity's Board of Directors or advisory committees; Kaleido: Consultancy, Current holder of stock options in a privately-held company, Membership on an entity's Board of Directors or advisory committees, Research Funding; Seres: Consultancy, Current holder of stock options in a privately-held company, Membership on an entity's Board of Directors or advisory committees, Patents & Royalties, Research Funding; LisCure: Consultancy, Membership on an entity's Board of Directors or advisory committees; MaaT Pharma: Consultancy, Membership on an entity's Board of Directors or advisory committees; Karius: Consultancy. Levine: Equillium Bio: Membership on an entity's Board of Directors or advisory committees; Incyte: Consultancy, Research Funding; Kamada: Research Funding; Biogen: Research Funding; Omeros: Membership on an entity's Board of Directors or advisory committees; Symbio: Membership on an entity's Board of Directors or advisory committees; Jazz Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees; Talaris Therapeutics: Membership on an entity's Board of Directors or advisory committees; Viracor: Patents & Royalties: GVHD biomarker patent with royalties from Viracor; Mesoblast: Consultancy, Research Funding; X4 Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees. Murthy: CRISPR Therapeutics: Research Funding. Riches: ATARA Biotherapeutics: Other: Payment; BioIntelect: Membership on an entity's Board of Directors or advisory committees; Jazz Pharmaceuticals: Other: Payment. Sung: Merck: Research Funding; Novartis: Research Funding; Enterome: Research Funding; Seres: Research Funding; AVROBIO: Consultancy; Abbott Nutrition: Honoraria; Clasado: Other: Research Product; DSM: Other: Research Product. Al Malki: Neximmune: Consultancy; Jazz Pharmaceuticals, Inc.: Consultancy; Rigel Pharma: Consultancy; Hansa Biopharma: Consultancy; CareDx: Consultancy. Rezvani: Kaleido: Other: One-time scientific advisory board; Nohla Therapeutics: Other: One-time scientific advisory board; Pharmacyclics-Abbvie: Research Funding; US Department of Justice: Consultancy. Bolaños-Meade: Incyte Corp: Consultancy. Holtan: Incyte: Consultancy, Research Funding; Generon: Consultancy. Saber: Govt. COI: Other. Hamadani: Sanofi, Genzyme, AstraZeneca, BeiGene: Speakers Bureau; Janssen, Incyte, ADC Therapeutics, Omeros, Morphosys, Kite: Consultancy; Takeda, Spectrum Pharmaceuticals and Astellas Pharma: Research Funding. Kean: Bluebird Bio: Research Funding; Bristol Myers Squibb: Patents & Royalties: From clinical trial data, Research Funding; Vertex: Consultancy; Novartis: Consultancy; Gilead: Research Funding; Regeneron: Research Funding; EMD Serono: Consultancy. Perales: Cidara: Honoraria; Servier: Honoraria; Incyte: Honoraria, Other; Equilium: Honoraria; Takeda: Honoraria; Novartis: Honoraria, Other; Nektar Therapeutics: Honoraria, Other; NexImmune: Honoraria; MorphoSys: Honoraria; Omeros: Honoraria; Karyopharm: Honoraria; Sellas Life Sciences: Honoraria; Merck: Honoraria; Miltenyi Biotec: Honoraria, Other; Medigene: Honoraria; Bristol-Myers Squibb: Honoraria; Kite/Gilead: Honoraria, Other; Celgene: Honoraria.

Abstract Background: Despite many treatment options, multiple myeloma (MM) remains largely incurable with poor outcomes among patients who progress after treatment with a protease inhibitor, immunomodulatory imide drugs (IMiDs), and/or an anti-CD38 antibody. Multiple targeted therapies have been developed for different subtypes of non-Hodgkin lymphoma (NHL); however, these therapies are typically not curative for patients with relapsed/refractory (R/R) disease. IMiDs are a standard of care for treatment of MM and have shown activity in some NHL subtypes. However, given that many patients treated with these agents frequently develop disease progression, an unmet need remains. CFT7455 is a next-generation IKZF1/3 degrader, which is more potent and catalytically active than other approved agents targeting the cereblon E3 ligase complex that degrade IKZF1/3. CFT7455 is orally bioavailable and selective for IKZF1 (Ikaros) and IKZF3 (Aiolos). Depletion of these targets from malignant B cells result in tumor cell death, and depletion from the tumor microenvironment results in T-cell activation. In i n vitro and in vivo models of MM and NHL, including anaplastic large cell lymphoma, diffuse large B-cell lymphoma, and mantle cell lymphoma (MCL), CFT7455 demonstrated greater activity than other agents in similar classes. These results provided rationale for a first-in-human, phase 1 study to evaluate CFT7455. Study Design: This is an open-label, multicenter, phase 1 clinical trial with dose escalation and dose expansion phases. The dose escalation phase, beginning with a starting dose of 50 mcg daily, may include single-participant cohorts at initial dose levels, after which 3-6 patients are enrolled per cohort using a Bayesian logistic regression model. After initial exploration of single-agent CFT7455 in a mixed cohort of patients with R/R MM or select NHLs, dose escalation is split to perform dose determination in R/R MM separate NHL. Once a safe dose of CFT7455 in R/R MM is determined, the combination of CFT7455 with dexamethasone will be explored in R/R MM. CFT7455 is dosed orally in 28-day cycles, on a 21-day on, 7-day off schedule, until disease progression or intolerable toxicity. Expansion cohorts of single-agent CFT7455 and CFT7455 plus dexamethasone in R/R MM, and single-agent CFT7455 for peripheral T-cell lymphoma and MCL are planned. Primary objectives include: safety and tolerability, randomized phase 2 dose (RP2D)/maximum tolerated dose (MTD) of CFT7455, and estimation of antitumor activity of CFT7455. Secondary objectives include assessment of pharmacokinetics. Exploratory objectives include characterization of target engagement and IKZF1/3 degradation and assessing the immunomodulatory effects of CFT7455. For MM patients, key inclusion criteria include histologically/cytologically-confirmed MM that is R/R. Patients must not be candidates for regimens known to provide clinical benefit, defined as having received ≥3 prior anti-myeloma regimens including ≥2 consecutive cycles of lenalidomide, pomalidomide, a proteasome inhibitor, a glucocorticoid, and an anti-CD38 antibody. Key exclusion criteria include the presence of central nervous system malignancy, recent venous thromboembolism or inability to undergo its prophylaxis. Plasma cell leukemia is excluded. For NHL patients, key inclusion criteria include histologically/cytologically-confirmed NHL that is R/R. Patients mustn't be candidates for regimens known to provide clinical benefit, defined as the requisite prior lines of therapy according to an indication-specific basis. Key exclusion criteria include the presence of central nervous system malignancy, recent venous thromboembolism or inability to undergo its prophylaxis. Several lymphoma subtypes less likely to benefit are excluded (eg, Richter transformation, Burkitt lymphoma, Sezary syndrome, and lymphoblastic lymphoma). Approximately 164 patients at approximately 13 US sites will be enrolled. This trial is registered with clinicaltrials.gov as NCT04756726, enrollment is ongoing. Disclosures Berdeja: Legend Biotech: Consultancy; Incyte: Research Funding; Ichnos Sciences: Research Funding; Genentech: Research Funding; GlaxoSmithKline: Research Funding; Lilly: Research Funding; SecuraBio: Consultancy; EMD Serono: Research Funding; Janssen: Consultancy, Research Funding; Bluebird bio: Consultancy, Research Funding; Amgen: Research Funding; Astex Pharmaceuticals: Research Funding; Kite Pharma: Consultancy; CRISPR Therapeutics: Consultancy, Research Funding; Celularity: Research Funding; Celgene: Consultancy, Research Funding; Poseida: Research Funding; Acetylon: Research Funding; Teva: Research Funding; Novartis: Research Funding; BMS: Consultancy, Research Funding; Sanofi: Research Funding; Abbvie: Research Funding; Takeda: Consultancy. Ailawadhi: GSK: Consultancy, Research Funding; Sanofi: Consultancy; Cellectar: Research Funding; Janssen: Consultancy, Research Funding; Xencor: Research Funding; Beigene: Consultancy; Karyopharm: Consultancy; BMS: Consultancy, Research Funding; Ascentage: Research Funding; Pharmacyclics: Consultancy, Research Funding; Amgen: Consultancy, Research Funding; AbbVie: Consultancy; Takeda: Consultancy; Genentech: Consultancy; Medimmune: Research Funding. Horwitz: Millennium /Takeda: Consultancy, Research Funding; Kura Oncology: Consultancy; Janssen: Consultancy; Tubulis: Consultancy; Myeloid Therapeutics: Consultancy; Affimed: Research Funding; Aileron: Research Funding; Vividion Therapeutics: Consultancy; ONO Pharmaceuticals: Consultancy; Celgene: Research Funding; Acrotech Biopharma: Consultancy; Daiichi Sankyo: Research Funding; Forty Seven, Inc.: Research Funding; Trillium Therapeutics: Consultancy, Research Funding; C4 Therapeutics: Consultancy; Kyowa Hakko Kirin: Consultancy, Research Funding; Seattle Genetics: Consultancy, Research Funding; SecuraBio: Consultancy, Research Funding; Shoreline Biosciences, Inc.: Consultancy; ADC Therapeutics: Consultancy, Research Funding; Verastem: Research Funding. Matous: Pharmacyclics: Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees. Mehta-Shah: C4 Therapeutics: Consultancy; Kiowa Hakko Kirin: Consultancy; Karyopharm: Consultancy; Ono Pharmaceuticals: Consultancy; Secura Bio: Consultancy, Research Funding; Daiichi Sankyo: Consultancy, Research Funding; AstraZeneca: Research Funding; Bristol Myers Squibb: Research Funding; Celgene: Research Funding; Innate Pharmaceuticals: Research Funding; Roche/Genentech: Research Funding; Corvus Pharmaceuticals: Research Funding; Verastem: Research Funding. Martin: GlaxoSmithKline: Consultancy; Sanofi: Research Funding; Oncopeptides: Consultancy; Amgen: Research Funding; Janssen: Research Funding. Richardson: Takeda: Consultancy, Research Funding; Sanofi: Consultancy; Secura Bio: Consultancy; Oncopeptides: Consultancy, Research Funding; GlaxoSmithKline: Consultancy; Regeneron: Consultancy; Protocol Intelligence: Consultancy; AstraZeneca: Consultancy; Karyopharm: Consultancy, Research Funding; Celgene/BMS: Consultancy, Research Funding; AbbVie: Consultancy; Janssen: Consultancy; Jazz Pharmaceuticals: Consultancy, Research Funding. Richard: Karyopharm, Janssen: Honoraria. Bhutani: Sanofi: Consultancy; Amgen, BMS, Takeda: Speakers Bureau; Janssen, MedImmune, Takeda, Celgene, BMS, Cerecor, Celularity: Research Funding. Yee: Takeda: Consultancy; Adaptive: Consultancy; Karyopharm: Consultancy; Bristol Myers Squibb: Consultancy; Oncopeptides: Consultancy; GSK: Consultancy; Amgen: Consultancy; Sanofi: Consultancy; Janssen: Consultancy. Palmer: C4 Therapeutics: Current Employment. Gorman: C4 Therapeutics: Current Employment. Schoenborn-Kellenberger: C4 Therapeutics: Current Employment. Bilic: C4 Therapeutics: Current Employment. Crystal: C4 Therapeutics: Current Employment, Current equity holder in publicly-traded company. Mahler: C4 Therapeutics: Current Employment, Current equity holder in publicly-traded company. Lonial: Merck: Honoraria; Abbvie: Consultancy, Honoraria; BMS/Celgene: Consultancy, Honoraria, Research Funding; TG Therapeutics: Membership on an entity's Board of Directors or advisory committees; Takeda: Consultancy, Honoraria, Research Funding; AMGEN: Consultancy, Honoraria; Janssen: Consultancy, Honoraria, Research Funding; GlaxoSmithKline: Consultancy, Honoraria, 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.

Abstract Background: In vitro studies and emerging clinical data suggest that inhibition of spleen tyrosine kinase may have an antileukemic effect in human AML. Pts with AML and TP53 mutations (TP53m) are commonly associated with older age (≥60 years) and complex karyotype (CK) and respond poorly to standard 7 + 3 induction (IND) chemotherapy with &lt;10% 1-year overall survival (OS). DEC has been reported to improve response in TP53m AML. Here, we report the results of a Phase 2 sub-study of the Beat AML Master Trial that assessed the efficacy of ENTO + DEC combination treatment (Tx) in ND AML patients (pts) with TP53m or CK aged ≥60 years. [ClinicalTrials.gov: NCT03013998] Methods: This multicenter (13 sites), open-label, Phase 2 combination Tx study utilized Simon's 2-stage Phase 2 design and enrolled AML pts with TP53m (identified molecularly) ± CK (Cohort A) or CK (≥3 metaphase abnormalities) without TP53m (Cohort B). Pts initially received 5 days of ENTO lead-in (which was later discontinued), followed by ENTO + DEC and those who achieved CR/CRh/CRi/MLFS with up to 3 cycles of IND proceeded to consolidation (CON) Tx for up to 11 cycles (Figure 1). Pts with CRi/MLFS after IND were allowed up to 6 cycles (IND + CON) to achieve CR/CRh or stayed on Tx if they got clinical benefit or went off Tx. CON was followed by maintenance (MTN) Tx for up to 2 years from start of study Tx. Pts were eligible if aged ≥60 years, ND, and had ECOG performance status 0 - 2. Pts received ENTO 400 mg orally twice daily for 5 days during ENTO lead-in, and then every 28 days during IND, CON, and MTN + DEC 20 mg/m 2 IV days 1-10 (IND) or days 1-5 (CON) every 28 days. Response was assessed using modified 2017 ELN AML criteria. The primary endpoint was composite complete remission (CCR) rate (CR + CRh) with up to 3 cycles of IND, and CRi/MLFS that achieved CR/CRh by up to 6 cycles (IND + CON). Beyond stage 1, pt accrual to Cohort A was allowed based on pts with CRi and to Cohort B was stopped early for futility. Results: Between Oct 2017 and Feb 2020, of the 63 pts enrolled (Cohort A = 48; Cohort B = 15), pts with confirmed eligibility who started study Tx were included in the analyses (Cohort A = 45; Cohort B = 13). During lead-in, 27 pts in Cohort A and 6 pts in Cohort B received ENTOm for 5 days. All pts received ENTO + DEC except 1 pt in Cohort A who withdrew consent (WOC). Median ages of the pts were 70 years (range 60 - 84) in Cohort A and 74 years (range 65 - 86) in Cohort B. Median time (range) on Tx was 2.2 mos and 4.8 mos in Cohort A and B, respectively. Most common reasons for Tx discontinuation were adverse event (AE; 27%), Tx failure (TF; 27%) and WOC (18%) in Cohort A; TF (31%), disease progression and relapse (each 15%) in Cohort B. In each cohort, 1 pt discontinued Tx due to death from leukemia and 1 pt in Cohort A in CRh due to development of an additional genetic abnormality. Four pts (9%) in Cohort A and 1 pt (8%) in Cohort B proceeded to transplant. The CCR (CR + CRh) rates with up to 6 cycles of Tx for Cohort A and B were 13.3% and 30.8%, respectively; overall CR + CRh rates were 17.8% and 38.5% (Table 1). In Cohort A, with a median follow-up of 11.5 months, 0% were 1-year disease-free and median OS (mOS) was 6.5 months. In Cohort B, with a median follow-up of 15.1 months, 25% were 1-year disease-free and mOS was 11.5 months. Deaths within 7-, 30-, and 60-days of Tx were 0, 3 and 11 in Cohort A and 0, 0 and 2 in Cohort B. Most common treatment-related Grade ≥3 AEs in Cohort A and B were febrile neutropenia (31% and 39%) and anemia (22% and 31%) (Table 2). Overall, 83 serious AEs (SAEs) were reported in 33 pts in Cohort A and 12 SAEs in 6 pts in Cohort B; most common SAEs in Cohort A were pneumonia (18%) and respiratory failure (11%), and in Cohort B sepsis, dehydration and acute kidney injury (each 15%). Most common treatment-related grade ≥3 laboratory abnormalities in Cohort A and B were neutrophils decreased (27% and 31%), WBC count decreased (20% and 23%), and lymphocyte count decreased (18% and 15%). Conclusions: ENTO + DEC demonstrated activity in ND AML pts aged ≥60 years with TP53m ± CK and CK without TP53 but induced low CR/CRh rates and short OS consistent with previously published poor CR rates and OS in these pts. Our results differ from the high remission rate and longer OS previously reported for DEC monotherapy in AML pts with TP53m. ENTO + DEC was safe and acceptably tolerated. Novel Tx strategies that can benefit AML pts with these most adverse risk factors are urgently needed. Figure 1 Figure 1. Disclosures Ruppert: Telios Pharma: Consultancy. 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. Borate: 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; Blueprint Medicine: Membership on an entity's Board of Directors or advisory committees; Genentech: Membership on an entity's Board of Directors or advisory committees, Other: Advisory Board; Pfizer: 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, Research Funding; AbbVie: Membership on an entity's Board of Directors or advisory committees, Research Funding; 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. Stein: Abbvie: Consultancy; Janssen Pharmaceuticals: Consultancy; Gilead Sciences, Inc.: Consultancy; Foghorn Therapeutics: Consultancy; Syros Pharmaceuticals, Inc.: Consultancy; Daiichi Sankyo: Consultancy; Blueprint Medicines: Consultancy; PinotBio: Consultancy; Genentech: Consultancy; Jazz Pharmaceuticals: Consultancy; Bristol Myers Squibb: Consultancy; Celgene: Consultancy; Agios Pharmaceuticals, Inc: Consultancy; Novartis: Consultancy; Astellas: Consultancy; Syndax Pharmaceuticals: 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; Janssen Pharmaceuticals: Research Funding; Amgen Inc.: Research Funding; Novartis: Research Funding; Stemline: Honoraria; Jazz Pharmaceutials: Honoraria. Blum: Amerisource Bergen; Abbvie, Syndax: Honoraria; Forma Therapeutics, Xencor; Celyad: Research Funding. Arellano: KITE Pharma, Inc: Consultancy; Syndax Pharmaceuticals, Inc: Consultancy. Schiller: Actinium Pharmaceuticals, Inc: Research Funding; Gamida Cell Ltd.: Research Funding; Pfizer: Current equity holder in publicly-traded company, Research Funding; Forma: Research Funding; Agios: Consultancy, Research Funding, Speakers Bureau; Constellation Pharmaceuticals: Research Funding; MedImmune: Research Funding; Ambit: Research Funding; Karyopharm: Research Funding; Daiichi-Sankyo: Research Funding; Incyte: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Kaiser Permanente: Consultancy; Abbvie: Research Funding; AstraZeneca: Consultancy; Genentech-Roche: Research Funding; Delta-Fly: Research Funding; Cyclacel: Research Funding; Mateon: Research Funding; Actuate: Research Funding; Onconova: Research Funding; Geron: Research Funding; Sangamo: Research Funding; Arog: Research Funding; Ariad: Research Funding; Stemline Therapeutics, Inc.: Honoraria, Research Funding, Speakers Bureau; Takeda: Research Funding; Trovagene: Research Funding; Ono-UK: Consultancy, Research Funding; Tolero: Research Funding; BMS/Celgene: Consultancy, Current equity holder in publicly-traded company, Research Funding, Speakers Bureau; Celator: Research Funding; Kite/Gilead: Honoraria, Research Funding, Speakers Bureau; Astellas: Honoraria, Research Funding, Speakers Bureau; Incyte: Consultancy; Novartis: Consultancy, Research Funding; Deciphera: Research Funding; FujiFilm: Research Funding; Samus: Research Funding; Regimmune: Research Funding; PrECOG: Research Funding; Amgen: Consultancy, Current equity holder in publicly-traded company, Honoraria, Research Funding, Speakers Bureau; Bio: Research Funding; Elevate: Research Funding; Jazz: Consultancy, Honoraria, Research Funding, Speakers Bureau; Biomed Valley Discoveries: Research Funding; Ono: Consultancy; Eli Lilly: Research Funding; Sellas: Research Funding; ASH foundation: Other: Chair-unpaid; Leukemia & Lymphoma Society: Research Funding; Bluebird Bio: Research Funding; Sanofi: Honoraria, Research Funding, Speakers Bureau; Pharma: Consultancy; Johnson & Johnson: Current equity holder in publicly-traded company; 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; Actinium: Honoraria; Amgen: Honoraria; Abbvie: Honoraria; Cellectis: Research Funding; Daiichi Sankyo: Research Funding; Genentech: Research Funding; Pfizer: Research Funding. Foran: certara: Honoraria; pfizer: Honoraria; syros: Honoraria; taiho: Honoraria; boehringer ingelheim: Research Funding; servier: Honoraria; revolution medicine: Honoraria; trillium: Research Funding; takeda: Research Funding; abbvie: Research Funding; novartis: Honoraria; bms: Honoraria; OncLive: Honoraria; gamida: Honoraria; sanofi aventis: Honoraria; aptose: Research Funding; actinium: Research Funding; kura: Research Funding; h3bioscience: Research Funding; aprea: Research Funding; sellas: Research Funding; stemline: Research Funding. Litzow: AbbVie: Research Funding; Omeros: Other: Advisory Board; Astellas: Research Funding; Pluristem: Research Funding; Jazz: Other: Advisory Board; Actinium: Research Funding; Amgen: 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. Cogle: Aptevo therapeutics: Research Funding; Celgene: Membership on an entity's Board of Directors or advisory committees. Vergilio: Foundation Medicine: Current Employment; Roche: Current equity holder in publicly-traded company. Gana: Bausch: Current holder of individual stocks in a privately-held company; The Leukemia & Lymphoma Society: Consultancy. Druker: The RUNX1 Research Program: Membership on an entity's Board of Directors or advisory committees; Aileron: 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; Recludix Pharma, Inc.: Consultancy; Third Coast Therapeutics: 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; VB Therapeutics: Membership on an entity's Board of Directors or advisory committees; GRAIL: Current equity holder in publicly-traded company; Iterion Therapeutics: Membership on an entity's Board of Directors or advisory committees; ALLCRON: Consultancy, 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; Aptose Therapeutics: Consultancy, Current equity holder in publicly-traded company, Membership on an entity's Board of Directors or advisory committees; Blueprint Medicines: Consultancy, Current equity holder in publicly-traded company, Membership on an entity's Board of Directors or advisory committees; Bristol-Myers Squibb: Research Funding; EnLiven: Consultancy, Research Funding; Merck & Co: Patents & Royalties; Pfizer: Research Funding; Nemucore Medical Innovations, Inc.: Consultancy; Cepheid: Consultancy, 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: Vincerx Pharmaceuticals: Current equity holder in publicly-traded company, Membership on an entity's Board of Directors or advisory committees; Novartis, Trillium, Astellas, AstraZeneca, Pharmacyclics, Syndax: Consultancy, Honoraria; Newave: Membership on an entity's Board of Directors or advisory committees. Levine: Isoplexis: Membership on an entity's Board of Directors or advisory committees; Gilead: Honoraria; Zentalis: Membership on an entity's Board of Directors or advisory committees; Imago: Membership on an entity's Board of Directors or advisory committees; Ajax: Membership on an entity's Board of Directors or advisory committees; Lilly: Honoraria; Prelude: Membership on an entity's Board of Directors or advisory committees; Amgen: Honoraria; Janssen: Consultancy; Celgene: Research Funding; Roche: Honoraria, Research Funding; Auron: Membership on an entity's Board of Directors or advisory committees; C4 Therapeutics: Membership on an entity's Board of Directors or advisory committees; Incyte: Consultancy; Astellas: Consultancy; Morphosys: Consultancy; QIAGEN: Membership on an entity's Board of Directors or advisory committees; Mission Bio: Membership on an entity's Board of Directors or advisory committees. OffLabel Disclosure: Off-label use of entospletinib and decitabine.

Abstract Introduction: Belantamab mafodotin (belamaf) is a B-cell maturation antigen (BCMA)-targeting antibody-drug conjugate approved in the United States (US) and Europe as a monotherapy for triple-class refractory adult patients with relapsed or refractory multiple myeloma (RRMM). This hypothesis-generating post-hoc analysis of DREAMM-2 trial (NCT03525678) data examined relationships between corneal exam findings (superficial punctate keratopathy and/or microcyst like epithelial changes), best-corrected visual acuity (BCVA), and direct patient-reported ocular symptoms per the Ocular Surface Disease Index (OSDI) questionnaire. This approach could provide insight into the relationship between corneal exam findings, BCVA, and ocular symptoms and their impact on quality of life to help determine if BCVA decline and symptoms could guide dosing. Currently, in the US, eye exams with eye-care professionals (ECPs) are required for each belamaf treatment, which can add to patients' therapy-related burden. Identifying a surrogate marker for results from corneal exam findings would help providers determine if dosing adjustments are necessary. Methods: Eye exams (including a corneal exam and BCVA assessment using the Snellen chart) were performed on all patients receiving single-agent belamaf (2.5 mg/kg) by ECPs at baseline (BL) and before each dose, administered q3w. Corneal exam findings (keratopathy) and BCVA were assessed per protocol-defined criteria, and grade (GR) assessment was based on the worst finding in the worse eye. BCVA and keratopathy grading were relative to BL. Patient-reported ocular symptoms and vision-related functioning, as per the OSDI, were used to evaluate the impact of treatment-related ocular toxicity. The OSDI is a patient-reported outcome questionnaire that assesses eye symptoms and effects on vision-related function in the past week and was performed in all patients before each belamaf dose. Items 1-5 address the frequency of eye-related symptoms (eg, painful or sore eyes, blurred vision) while items 6-9 address the frequency of functional limitations (eg, driving at night or reading). OSDI was considered positive, clinically meaningful, and potentially associated with treatment when at least one question 1-5 (ie, sensitivity to light, gritty or painful eyes, blurred or poor vision) was reported as experienced "all of the time" and at least one question 6-9 (ie, driving at night, reading, working with PC, or watching TV) was reported as experienced "most of the time." Results: Overall, GR 3-4 (severe) keratopathy was observed only 5% of the time in patients who did not report frequent ocular symptoms as measured by the OSDI questionnaire (no items 1-9 ≥ "most of the time"). A further breakdown of the questions revealed that, in patients who reported no items 1-5 "all of the time" AND no items 6-9 ≥ "most of the time" (OSDI negative), GR 3-4 keratopathy was observed only 6% of the time (Table). When considering individual OSDI items, in patients who reported "no deterioration from BL" for any of the OSDI eye-related symptoms or functional limitations, GR 3-4 keratopathy was observed ~3%-7% of the time while GR 0-2 (mild) keratopathy was observed ~23%-34% of the time. Similar results were observed in patients with BCVA ≤20/30 at BL who reported "no deterioration from BL" for any eye-related adverse events (AEs) or functional limitations (GR 3-4 keratopathy: ~2%-6% of the time; GR 0-2 keratopathy: ~19%-28% of the time); patients with worse visual acuity at BL (BCVA &gt;20/30) who reported "no deterioration" for items 1-9 had lower incidence of GR 3-4 and GR 0-2 keratopathy (~0%-1% and ~3%-8%, respectively). Conclusions: The results from this hypothesis-generating post-hoc analysis suggest that hematologists/oncologists may be able to use clinical indicators/tools (eg, ocular symptoms, the OSDI tool) as potential surrogate markers for eye exam results to help determine whether dosing changes are needed. This approach will be explored in trials with other belamaf dose regimens that are currently under evaluation. If the results are validated, it may be possible for hematologists/oncologists to manage belamaf dose modifications, due to ocular AEs, without a confirmatory eye exam by the ECP, reducing the patient burden. Funding Source: GSK (205678). Drug linker technology licensed from Seagen; monoclonal antibody produced using POTELLIGENT Technology licensed from BioWa. Figure 1 Figure 1. Disclosures Popat: Takeda: Honoraria, Other: TRAVEL, ACCOMMODATIONS, EXPENSES; GlaxoSmithKline: Consultancy, Honoraria, Research Funding; AbbVie, BMS, Janssen, Oncopeptides, and Amgen: Honoraria; Abbvie, Takeda, Janssen, and Celgene: Consultancy; Janssen and BMS: Other: travel expenses. Badros: GlaxoSmithKline: Research Funding; BMS: Research Funding; Janssen: Research Funding; J&J: Research Funding. Kumar: Abbvie: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Amgen: Consultancy, Research Funding; Takeda: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Tenebio: Research Funding; Antengene: Consultancy, Honoraria; Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Carsgen: Research Funding; Roche-Genentech: Consultancy, Research Funding; Beigene: Consultancy; BMS: Consultancy, Research Funding; KITE: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Bluebird Bio: Consultancy; Oncopeptides: Consultancy; Astra-Zeneca: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Research Funding; Merck: Research Funding; Adaptive: Membership on an entity's Board of Directors or advisory committees, Research Funding; Sanofi: Research Funding. Rodríguez-Otero: Regeneron: Membership on an entity's Board of Directors or advisory committees; Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Oncopeptides: Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Kite: 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; Sanofi: Honoraria, Membership on an entity's Board of Directors or advisory committees; GlaxoSmithKline: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; BMS/Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel and other expenses. Cohen: BMS: Research Funding; GlaxoSmithKline: Other: Personal fees and other association with, Research Funding; Novartis: Research Funding; Celgene: Honoraria, Other: Personal fees and other association with; Janssen: Honoraria; Kite Pharma: Honoraria; Oncopeptides: Honoraria; Seattle Genetics: Honoraria; Takeda: Honoraria. Manier: Regeneron: Consultancy, Research Funding; Oncopeptides: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Abbvie: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Adaptive Biotechnologies: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; GSK: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Amgen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Consultancy, Research Funding; Celgene - Bristol Myers Squibb: 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; Roche: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding. Voorhees: Secura Bio: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Abbvie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; BMS: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; GlaxoSmithKline: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Karyopharm: 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; Oncopeptides: 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; Sanofi: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees. Gay: Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees; Bristol-Myers Squibb: Honoraria; AbbVie: Honoraria, Membership on an entity's Board of Directors or advisory committees; GlaxoSmithKline: Honoraria, Membership on an entity's Board of Directors or advisory committees; Roche: Membership on an entity's Board of Directors or advisory committees; Adaptive Biotechnologies: Membership on an entity's Board of Directors or advisory committees; Oncopeptides: Membership on an entity's Board of Directors or advisory committees; Bluebird Bio: Membership on an entity's Board of Directors or advisory committees; Sanofi: Consultancy, Honoraria. Rifkin: Takeda: Membership on an entity's Board of Directors or advisory committees; Sanofi: Membership on an entity's Board of Directors or advisory committees; Fresenius-Kabi: Membership on an entity's Board of Directors or advisory committees; Coherus: Membership on an entity's Board of Directors or advisory committees; Bristol Myers Squibb (Celgene): Membership on an entity's Board of Directors or advisory committees; Amgen: Membership on an entity's Board of Directors or advisory committees; McKesson: Current Employment, Current equity holder in publicly-traded company; Karyopharm: Membership on an entity's Board of Directors or advisory committees. Martin: Janssen: Research Funding; Sanofi: Research Funding; Oncopeptides: Consultancy; Amgen: Research Funding; GlaxoSmithKline: Consultancy. Chari: Oncopeptides: Consultancy, Membership on an entity's Board of Directors or advisory committees; Takeda: Consultancy, Research Funding; GlaxoSmithKline: Consultancy, Membership on an entity's Board of Directors or advisory committees; Secura Bio: Consultancy, Membership on an entity's Board of Directors or advisory committees; Shattuck Labs: 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; Seattle Genetics: Membership on an entity's Board of Directors or advisory committees, Research Funding; Antengene: Consultancy, Membership on an entity's Board of Directors or advisory committees; Novartis: Consultancy, Research Funding; Pharmacyclics: Research Funding; Millenium/Takeda: Consultancy, Research Funding; Sanofi Genzyme: Consultancy, Membership on an entity's Board of Directors or advisory committees; Karyopharm: Consultancy, Membership on an entity's Board of Directors or advisory committees; Amgen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; BMS/Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen Oncology: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding. Weisel: Bristol Myers Squibb: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Oncopeptides: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Roche: Honoraria; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Sanofi: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; GSK: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Karyopharm: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Adaptive Biotechnologies: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Abbvie: Consultancy; Novartis: Honoraria; Pfizer: Honoraria. Farooq: Five Prime Therapeutics/Amgen: Consultancy; GlaxoSmithKline: Consultancy. Jeng: OysterPoint: Consultancy; GlaxoSmithKline: Consultancy, Honoraria, Research Funding; Sanofi: Consultancy; Eyegate: Current equity holder in publicly-traded company. Chng: Abbvie: Consultancy; GlaxoSmithKline: Consultancy; Takeda: Consultancy; BMS/Celgene: Consultancy, Research Funding; Sanofi: Consultancy; Novartis: Research Funding; Johnson & Johnson: Consultancy, Research Funding; Amgen: Consultancy; Antengene: Consultancy; Pfizer: Consultancy; Aslan: Research Funding. Lee: Takeda Pharmaceuticals: Consultancy, Research Funding; Oncopetides: Consultancy; Sanofi: Consultancy; GlaxoSmithKline: Consultancy, Research Funding; Legend Biotech: Consultancy; Karyopharm: Consultancy; Janssen: Consultancy, Research Funding; Genentech: Consultancy; Celgene: Consultancy; Bristol Myers Squibb: Consultancy; Amgen: Consultancy, Research Funding; Regeneron: Research Funding. Berdeja: BMS: Consultancy, Research Funding; Celgene: Consultancy, Research Funding; Celularity: Research Funding; CRISPR Therapeutics: Consultancy, Research Funding; Janssen: Consultancy, Research Funding; Kite Pharma: Consultancy; Legend Biotech: Consultancy; SecuraBio: Consultancy; EMD Serono: Research Funding; Genentech: Research Funding; GlaxoSmithKline: Research Funding; Ichnos Sciences: Research Funding; Incyte: Research Funding; Novartis: Research Funding; Poseida: Research Funding; Bluebird bio: Consultancy, Research Funding; Astex Pharmaceuticals: Research Funding; Amgen: Research Funding; Abbvie: Research Funding; Takeda: Consultancy; Sanofi: Research Funding; Acetylon: Research Funding; Teva: Research Funding; Lilly: Research Funding. Jadhav: GlaxoSmithKline: Current Employment, Current equity holder in publicly-traded company. Tosolini: GlaxoSmithKline: Current Employment, Current equity holder in publicly-traded company. Eliason: GlaxoSmithKline: Current Employment, Current equity holder in publicly-traded company. Palumbo: GlaxoSmithKline: Current Employment, Current equity holder in publicly-traded company. Dimopoulos: Beigene: Honoraria; BMS: Honoraria; Amgen: Honoraria; Janssen: Honoraria; Takeda: Honoraria. Lonial: Merck: Honoraria; Janssen: Consultancy, Honoraria, Research Funding; BMS/Celgene: Consultancy, Honoraria, Research Funding; AMGEN: Consultancy, Honoraria; GlaxoSmithKline: Consultancy, Honoraria, Research Funding; Abbvie: Consultancy, Honoraria; Takeda: Consultancy, Honoraria, Research Funding; TG Therapeutics: Membership on an entity's Board of Directors or advisory committees. Trudel: Amgen: Consultancy, Honoraria, Research Funding; Takeda: Honoraria; Amgen Canada: Honoraria; Sanofi: Honoraria; Celgene: Consultancy, Honoraria, Research Funding; GlaxoSmithKline: Consultancy, Research Funding; Janssen: Honoraria, Research Funding; Genentech: Research Funding; Karyopharm: Honoraria. Richardson: Sanofi: Consultancy; Celgene/BMS: Consultancy, Research Funding; Protocol Intelligence: Consultancy; GlaxoSmithKline: Consultancy; Secura Bio: Consultancy; AbbVie: Consultancy; Karyopharm: Consultancy, Research Funding; Janssen: Consultancy; Oncopeptides: Consultancy, Research Funding; Regeneron: Consultancy; AstraZeneca: Consultancy; Takeda: Consultancy, Research Funding; Jazz Pharmaceuticals: Consultancy, Research Funding. Terpos: Celgene: Consultancy, Honoraria, Research Funding; Genesis: Consultancy, Honoraria, Research Funding; GSK: Honoraria, Research Funding; Amgen: Consultancy, Honoraria, Research Funding; BMS: Honoraria; Janssen-Cilag: Consultancy, Honoraria, Research Funding; Novartis: Honoraria; Takeda: Consultancy, Honoraria, Research Funding; Sanofi: Consultancy, Honoraria, Research Funding.