ALBERT

Description: Background Despite advances in therapy, relapsed or refractory (RR) non-Hodgkin lymphoma (NHL) remains a major treatment challenge. Preclinical data support the activity of proteasome inhibitors against lymphoma through multiple mechanisms including activation of the endoplasmic reticulum (ER) stress response and reduction in the threshold for apoptosis in response to chemotherapy. Clinically, proteasome inhibiton with bortezomib added to bendamustine yielded promising results in patients (pts) with indolent NHL with limited additional toxicity. Compared to bortezomib, carfilzomib is a more target specific and potent proteasome inhibitor with less neurotoxicity. We embarked on a multicenter, phase 1b dose escalation trial to assess the combination of carfilzomib with bendamustine and rituximab in pts with RR aggressive or indolent NHL. Methods The primary objective of the study is to determine the maximum tolerated dose (MTD) and recommended phase II dose of carfilzomib when combined with bendamustine and rituximab. The secondary objective is to evaluate the preliminary antitumor activity of the combination in select NHL histologies. Correlative studies examine markers of ER stress and apoptosis in response to treatment. Here we report the preliminary results of the dose escalation phase expected to be completed in Fall 2019. We followed a standard 3+3 design with escalation of the carfilzomib dose in 4 dose level cohorts combined with bendamustine dosed at 90 mg/m2 IV on Days 1 and 2 and Rituximab dosed at 375 mg/m2 IV on Day 9 of cycle 1 and Day 1 of subsequent cycles. Initially, carfilzomib was dosed twice a week with dose level 1 at 15 mg/m2 IV on days 1,2,8,9, 15, and 16. Subsequently, we explored weekly dosing schedules with carfilzomib at 36 mg/m2 (dose level 2), 56 mg/m2 (dose level 3), and 70 mg/m2 (dose level 4) on days 9 and 16 with a 20 mg/m2 starting dose on day 2. Dose limiting toxicity (DLT) was defined as Gr4 or specific Gr3 events attributable to the combination. Pts are treated for up to 6 cycles with an interim PET/CT after cycle 3. Results To date, 10 pts have been treated on the dose escalation phase with one patient currently on study treatment. Overall, 5 pts had diffuse large B-cell lymphoma (DLBCL), 3 mantle cell lymphoma (MCL), 1 follicular lymphoma (FL), and 1 marginal zone lymphoma (MZL). Pts received a median of 3 prior lines of therapy. Four pts were treated on dose level 1, 3 on dose level 2, and 3 on dose level 3. Treatment-emergent Grade 2-4 adverse events included thrombocytopenia in 1 pt (Gr 4), neutropenia in 1 pt (Gr 4), febrile neutropenia in 1 pt (Gr 3), culture negative fevers in 1 pt (Gr 3), nausea/vomiting in 2 pts (Gr 2 and 3), other GI toxicities in 1 pt (Gr 2), lower back pain in 1 pt (Gr 2), arthralgias in 1 pt (Gr 2), and cerebrevoascular ischemia in 1 pt (Gr 2). Two pts had treatment related-SAEs (Gr3 culture negative fevers; Gr 3 febrile neutropenia and Gr 3 vomiting) at dose level 2 and 3 respectively. One patient experienced DLT (Gr 3 febrile neutropenia) at dose level 3. There were no treatment related deaths. Of 10 evaluable pts to date, the overall response rate (ORR) is 40% with 3 pts achieving complete remission (one with FL, one with DLBCL and one with MCL) and one pt with MCL achieving a partial remission. The responder with FL had relapsed disease after achieving prior complete remission with rituximab and bendamustine alone. For the 9 pts who completed study treatment, median duration of treatment was 2.4 months, median progression free survival was 1.9 months and median overall survival was 11.6 months. The median duration of response for the 3 responders who completed therapy was 21.8 months. Conclusion Carfilzomib in combination with bendamustine and rituximab is a safe and well-tolerated treatment for pts with RR NHL. The MTD has not been reached and enrollmemt continues, with dose escalation phase anticipated to complete in Fall 2019. Preliminary data indicate that this combination may have efficacy with an acceptable side effect profile in this heavily pre-treated patient population with limited treatment options. Disclosure: This study was approved and funded by the National Comprehensive Cancer Network (NCCN) Oncology Research Program with general research support provided by Amgen. Disclosures Tuscano: Spectrum: Research Funding; Celgene: Honoraria, Research Funding; Novartis: Research Funding; Pharmacyclics: Research Funding; Seattle Genetics: Honoraria; Amgen: Honoraria; Takada: Research Funding; Abbvie: Research Funding; Genentech: Research Funding. Wieduwilt:Celgene: Membership on an entity's Board of Directors or advisory committees; Amgen, Leadiant, Merck, Servier: Research Funding; Daiichi Sankyo: Membership on an entity's Board of Directors or advisory committees; Reata Pharmaceuticals: Equity Ownership. Andreadis:Genentech: Equity Ownership, Other: Spouse is Employee; Novartis: Honoraria, Research Funding; Amgen: Consultancy, Research Funding; Celgene: Consultancy, Research Funding; Gilead: Consultancy; Jazz Pharmaceuticals: Consultancy; Bayer: Consultancy.

Description: Background Despite recent advances, treatment of relapsed refractory multiple myeloma (RRMM) remains a challenge. Venetoclax, a BH3 mimetic, is an oral, specific, and potent small molecule inhibitor of BCL-2 that has been approved for treatment of 17p-deleted CLL and in combination with azacitidine or decitabine in AML patients 〉/= 75 years of age.Pre-clinical and clinical studies suggest that bcl-2 inhibition can induce MM cell death and may synergize with bortezomib and dexamethasone. Based on this, several prospective clinical trials of venetoclax in RRMM have been performed. However, clinical use of this targeted therapeutic for salvage therapy in RRMM has not been well described. Methods We performed a single-center, retrospective chart review of all patients with RRMM diagnosed after January 1, 2009 who were treated with off-label use of venetoclax. The goal of this study was to describe the clinical characteristics of these patients, assess the response to salvage treatment with venetoclax as determined by the International Myeloma Working Group (IMWG) criteria, and assess the toxicities during salvage treatment with venetoclax in an academic practice setting. Results 43 patients were identified. Median number of lines of prior therapy was 7 (range 2-13). 12 patients had documented high risk cytogenetics, defined as the presence of a 17p deletion, t(14;16), t(14;20), t(4,14), gain (1q), or nonhyperdiploidy. Of the 36 patients with cytogenetics/FISH available, 8 had t(11;14). 34 patients were refractory to bortezomib. 40 patients had progressed after carfilzomib, 36 after pomalidomide, and 41 after anti-CD38 antibody therapy. 39 patients were treated with venetoclax in combination with a proteasome inhibitor (bortezomib (n=36); carfilzomib (n=3)). 23 patients were treated with venetoclax, proteasome inhibitor, and dexamethasone. Patients were started at 400 mg daily for 7 days then increased to the median dose of 800mg daily (11 received 〈 800mg/daily as a final dose and one received 〉800 mg/daily as final dose). Overall patients were on treatment for a median of 67 days (range 2-855). 2 patients received intermittent venetoclax therapy, defined as being off venetoclax for at least 3 months before restarting. Best response by IMWG criteria include; CR 5%( 2/43), VGPR 12% (5/43) and PR 16% (7/43) for an overall response rate of 33% (14/43). In addition, MR was seen in 5% (2/43) and stable disease in 9% (4/43). Fifty-one percent (22/43) had progressive disease (PD). Out of the 8 patients who had t(11;14), best responses were: 2 VGPR, 2 PR, 1 SD, and 3 PD for a response rate of 50% (4/8) in this subgroup. Median time to best response for all responding patients was 90 days (range 15-305) and median duration of response was 206 days (range 28-820). At time of data collection, median follow-up time from venetoclax treatment initiation was 192 days (range 8-1058). Four patients have not progressed and remain on therapy, 23 patients remain alive, and 4 patients have been lost to follow-up for over 6 months. The most common treatment related AEs were cytopenias including leukopenia in 26 /43 (60%) patients, neutropenia in 19/43 (44%) patients, and thrombocytopenia in 22/43 (51%) patients. Non-hematologic toxicities included diarrhea in 12/43 (30%) patients, nausea/vomiting in 15/43 (35%) patients, infections in 11/43 (26%) patients, and fatigue in 23/43 (53%) patients. 8/43 (19%) patients required dose reduction, 7/43 (16%) patients required temporary discontinuation of treatment, and 4/43 (9%) patients required permanent discontinuation due to treatment related AEs. 38/43 (88%) patients had any grade treatment related AEs, 27/43 (63%) patients had grade 〉/= 3 AEs and 2/43 (5%) patients had treatment related SAEs. One patient had a treatment related death from an infectious complication (CMV pneumonitis). Conclusions Venetoclax is an active and well-tolerated agent in relapsed multiple myeloma. Furthermore, it is easily administered in the outpatient setting. Additional areas of research with this therapy include understanding the importance of t(11:14) for response and selecting the best anti-MM partner for combination therapy. Disclosures Ledergor: Venetoclax: Other: off-label use; Immunai: Consultancy. Martin:Roche and Juno: Consultancy; Amgen, Sanofi, Seattle Genetics: Research Funding. Wolf:Takeda: Consultancy; Celgene: Consultancy; Novartis: Consultancy; Janssen: Consultancy; Amgen: Consultancy. Wong:Celgene Corporation: Research Funding; Genentech: Research Funding; Janssen: Research Funding; Fortis: Research Funding; Juno: Research Funding. Shah:Nkarta: Consultancy, Membership on an entity's Board of Directors or advisory committees; Celgene, Janssen, Bluebird Bio, Sutro Biopharma: Research Funding; Bristol-Myers Squibb: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Poseida: Research Funding; Genentech, Seattle Genetics, Oncopeptides, Karoypharm, Surface Oncology, Precision biosciences GSK, Nektar, Amgen, Indapta Therapeutics, Sanofi: Membership on an entity's Board of Directors or advisory committees; University of California, San Francisco: Employment; Indapta Therapeutics: Equity Ownership; Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Kite: Consultancy, Membership on an entity's Board of Directors or advisory committees; Teneobio: Consultancy, Membership on an entity's Board of Directors or advisory committees. OffLabel Disclosure: This study is looking at the safety and efficacy of venetoclax in relapsed refractory myeloma patients who are treated off-label since venetoclax is not currently approved for multiple myeloma

Description: Background: Chimeric antigen receptor T-cell (CAR T) immunotherapy is an evolving treatment for relapsed/ refractory non-Hodgkin lymphoma (NHL) and multiple myeloma (MM). There is a growing need to elucidate the infectious complications of BCMA- and CD19-directed CAR T therapy. We performed a single-center retrospective analysis of infection outcomes up to 1-year post BCMA and CD19-directed CAR T treatment. Methods: All patients treated at our institution with a BCMA-directed CAR T therapy for MM or with a CD19-directed CAR T for NHL from 2018-2020 were analyzed for risk factors for infection and infectious complications. Bacterial, viral and fungal infections were recorded if there was a microbiologic or histopathologic diagnosis or if clinical suspicion for infection required empiric treatment. Infection severity was classified as mild, moderate, severe, life-threatening, or fatal as previously described (Young et al. 2016, van Burnik et al. 2007). Infections were identified from the day of the first CAR T-cell infusion up to 1 year after infusion. Observation of infections was terminated at the time of disease progression, initiation of next therapy, or death, whichever occurred first. Fisher's exact test and Wilcoxon rank-sum test were used to compare between cohorts. Poisson mixed effects model with a subject-specific random intercept and an offset to account for the duration at risk was used to identify risk factors for infections. Results: Of the 104 subjects in this study, 55 patients (53%) had MM treated with BCMA CAR T and 49 patients (47%) had NHL treated with CD19 CAR T. Median number of prior therapies was 6 (4 - 9) in the BCMA cohort and 3 (2-4) in the CD19 cohort (Table 1). Prior to starting lymphodepleting (LD) chemotherapy, most patients did not have IgG〈 400, ALC〈 200, or ANC〈 500. Almost all the patients were on antibacterial (99%), antiviral (99%) and antifungal (92%) prophylaxis (ppx), with 18%, 90% and 9% of patients starting this before LD chemotherapy, respectively. Median follow-up time was 5.8 months (95% CI: 4.2-6.4). In total, there were 87 infection events (48 bacterial, 33 viral, and 6 fungal) observed in 56 patients (54%), with 47 infections in 29 (53%) patients in the BCMA CAR T cohort and 40 infections in 27 (55%) patients in the CD19 CAR T cohort (p =0.9). The BCMA cohort had 19 bacterial (40%) vs 29 bacterial (73%) in CD19 cohort (p=0.005), while BCMA cohort had 25 viral (53%) vs 8 viral (20%) in CD19 cohort (p=0.002). Fungal infection rates were comparable between BCMA and CD19 cohorts, 3 (6%) vs 3 (8%) respectively (p=1). Among the infections that occurred, 20 (23%) were high severity occurring in 16 patients (15%) of the overall cohort. Four high severity infections (5%) occurred in 3 patients (5%) in the BCMA cohort while 16 high severity infections (18%) occurred in 13 patients (27%) in the CD19 cohort (p 〈 0.001) (Figure 1). The BCMA cohort had higher rates of respiratory infections (68% vs 50%, p=0.1), while the CD19 cohort had higher rates of bloodstream infections (15% vs 2%, p=0.05) and gastrointestinal infections (10% vs 0%, p=0.04). The rates of grade (Gr) 3-4 neutropenia and IgG 〈 300 in both the cohorts at various time points post CAR T were comparable. At 9-12 months, Gr 3-4 neutropenia was 7% vs 8% (p=1) and IgG 〈 300 was 7% vs 33% (p=0.1) for the BCMA and CD19 cohorts respectively. Adjusting for time periods, risk factors for development of infections were use of steroids (incidence rate ratio [IRR] 1.6, 95% CI: 1.1-2.5, p=0.03) and post CAR T hypogammaglobulinemia (IgG 〈 600) (IRR =2.1, 95% CI: 1.2-3.9, p=0.02). Conclusions: This retrospective study is one of the largest studies to date comparing the post CAR T infections rates between BCMA and CD19 directed CAR T treated patients. While the incidence of infection, use of antimicrobial ppx, and rates of Gr 3-4 neutropenia and hypogammaglobulinemia were comparable between BCMA and CD19 CAR T cohorts, viral infections were more common post BCMA CAR T while bacterial infections were more frequent post CD19 CAR T. Use of steroids as well as post CAR T hypogammaglobulinemia are possible risk factors for development of infections. Further studies are needed to examine the infectious complications post-CAR T treatment, characterize the underlying risk factors, and to establish appropriate prophylactic approaches in patients undergoing CD19- and BCMA-directed CAR T therapy. Disclosures Fakhri: University of California San Francisco: Current Employment. Ai:Nurix Therapeutics: Membership on an entity's Board of Directors or advisory committees, Research Funding; ADC Therapeutics, Kymera: Membership on an entity's Board of Directors or advisory committees. Martin:Seattle Genetics: Research Funding; GSK: Consultancy; Sanofi: Research Funding; AMGEN: Research Funding; Janssen: Research Funding. Wolf:Adaptive: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Shah:BMS, Janssen, Bluebird Bio, Sutro Biopharma, Teneobio, Poseida, Nektar: Research Funding; GSK, Amgen, Indapta Therapeutics, Sanofi, BMS, CareDx, Kite, Karyopharm: Consultancy. Andreadis:Genentech: Other: Spouse Employee (salary and stock); Novartis: Research Funding; Celgene/Juno: Research Funding; Amgen: Research Funding; Merck: Research Funding; Gilead/Kite: Other: Advisor; Jazz Pharmaceuticals: Other: Advisor; Astellas: Other: Advisor; Seattle Genetics: Other: Advisor; Karyopharm: Other: Advisor; Incyte: Other. Wong:GSK: Research Funding; Amgen: Consultancy; Sanofi: Membership on an entity's Board of Directors or advisory committees; Bristol Myers Squibb: Research Funding; Roche: Research Funding; Janssen: Research Funding; Fortis: Research Funding.

Description: Background: Daratumumab, a human anti-CD38 monoclonal antibody, is approved in many countries for use as monotherapy in relapsed/refractory multiple myeloma (RRMM), and in combination with standard-of-care regimens in RRMM. The phase 2 DARAZADEX study will evaluate the efficacy and safety of daratumumab plus azacitidine and dexamethasone in RRMM patients previously treated with daratumumab. Pre-clinical data from our laboratory has demonstrated that azacitidine induces a 1.2 - 2.4 increase in CD38 median fluorescent intensity (MFI) in a dose-dependent manner across four different MM cell lines. (Figure 1A) Using an immortalized transgenic natural killer (NK) cell line to mediate lysis, we observed a significant increase in antibody-dependent cell-mediated cytotoxicity (ADCC) in the azacitidine-treated MM cells as opposed to control. Importantly, this increase in ADCC correlated with CD38 MFI upregulation. (Figure 1B). Based on this data we hypothesize that azacitidine, by upregulating the expression of CD38, can potentially increase the ADCC and efficacy of daratumumab on multiple myeloma cells and help reverse daratumumab resistance. Methods: In this single-arm, 2-stage, phase II study, approximately 23 RRMM patients in the United States will be treated with combination of daratumumab, azacitidine, and dexamethasone. Eligible patients must have progressed on ≥2 lines of prior therapy, including an immunomodulatory drug (IMiD) and proteasome inhibitor, and have previously been treated with daratumumab with most recent daratumumab treatment being at least 6 months prior to enrollment to allow for CD38 normalization. Patients who were previously primary refractory to daratumumab will be excluded from the study. Patients will receive azacitidine at the standard 75 mg/m2 dose 5 days consecutively every 4 weeks starting day -7 to day -3 of Cycle 1 and then Day 22-26 of Cycle 1-3, and subsequently Day 1-5 of Cycle 5 and thereafter until disease progression or intolerance, with dose modifications for toxicities. Daratumumab will be administered intravenously at the standard dose of 16 mg/kg, with first dose administered on day 1. Daratumumab will be dosed in standard fashion: weekly for 8 doses (induction phase), every two weeks for 8 doses (consolidation phase), and then every 4 weeks thereafter (maintenance phase). Daratumumab will be switched to the subcutaneous formulation at a later timepoint. There will be no dose modifications for daratumumab. Dexamethasone at a dose of 40 mg PO (or IV if PO is not available) will be given weekly for Cycle 1 and 2, after which the pre-infusion medication dose can be reduced to 20 mg and non-pre-infusion dose can be reduced or stopped based on investigator's discretion. Bone marrow biopsies will be done within 14 days prior to Cycle 1 day -7 (first azacitidine dose) and on Cycle 1 day 1 prior to first daratumumab infusion (or after completion of first 5 days of azacitidine and prior to first daratumumab infusion), for correlative studies. (Figure 1C) Simon's minimax two-stage design will be used with a safety lead-in cohort of 6 patients. In the first stage, a total of 13 patients will be enrolled (including the safety cohort), and if there is ≥2 responses in 13 patients the study will enroll an additional 10 patients; if there is ≤ 1 responses in 13 patients the study will be stopped. Primary objective is to evaluate the efficacy, as determined by the overall response rate (ORR) of this combination. Secondary objectives include duration of response per international myeloma working group (IMWG) criteria, safety and toxicity, and the 1-year OS and PFS of this combination. An additional secondary objective is to evaluate the changes in CD38 expression on plasma cells induced by azacitidine in patients with RRMM and identify any correlation of this change with depth and duration of response. The exploratory objective will be to evaluate the tumor microenvironment changes induced by azacitidine via mass cytometry (CyTOF). NCT04407442. Figure 1 Disclosures Wong: Bristol Myers Squibb: Research Funding; GSK: Research Funding; Janssen: Research Funding; Sanofi: Membership on an entity's Board of Directors or advisory committees; Amgen: Consultancy; Roche: Research Funding; Fortis: Research Funding. Martin:Janssen: Research Funding; GSK: Consultancy; Seattle Genetics: Research Funding; Sanofi: Research Funding; AMGEN: Research Funding. Wolf:Adaptive: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Shah:GSK, Amgen, Indapta Therapeutics, Sanofi, BMS, CareDx, Kite, Karyopharm: Consultancy; BMS, Janssen, Bluebird Bio, Sutro Biopharma, Teneobio, Poseida, Nektar: Research Funding. OffLabel Disclosure: Azactidine is being used off-label in multiple myeloma

Description: Introduction: Chimeric antigen receptor modified T Cell (CAR-T) therapy is a rapidly developing treatment for patients with relapsed/refractory (R/R) B-cell non-Hodgkin lymphoma (NHL) or multiple myeloma (MM). Although this population is at high risk for thrombosis, there are few data about rates of venous thromboembolism (VTE) and arterial thromboembolism (ATE) with CAR-T. Additionally, treatment with anticoagulation is complicated because of the prevalence of thrombocytopenia following CAR-T. Our goal was to determine the incidence, associated risk factors, management and outcomes of VTE and ATE in the 60 days following CAR-T therapy. Methods: We performed a single-center, retrospective cohort study of all patients who received inpatient CAR-T cells at UCSF Medical Center between January 2018 and May 2020 for R/R NHL or MM as standard-of-care or on a clinical trial. The outcomes of incident VTE and ATE were identified by ICD-10 codes and medical record review. Patient characteristics, pre-existing thrombosis risk factors, laboratory results, medications, and major or clinically relevant non-major bleeding or recurrent thrombotic complications were obtained through chart review. We used descriptive statistics to delineate risk factors, incidence, management and outcomes of thrombotic events. Results: Ninety-one patients who underwent CAR-T therapy were included in the analysis, 37 with NHL and 54 with MM. For NHL, mean age was 63 (range 38-82), and 41% were women. For MM, mean age was 62 (range 33-77), and 50% were women. Patients with NHL were treated with either investigational or Federal Drug Administration-approved CD19-directed therapies, and patients with MM were treated with a variety of investigational B-cell maturation antigen-directed (BCMA) therapies. For thrombotic risk factors, 13% of patients with NHL had a history of VTE, 3% had a history of ATE, 27% had a BMI ≥30, 59% had a recent procedure including central venous catheter (CVC) placement, 14% had an intensive care unit (ICU) stay, and 22% had an infectious complication in the 30 days pre- or post-CAR-T. Forty-one percent of patients with NHL had neurotoxicity of any grade, and 59% had CRS of any grade. At 30 days, 57% had a complete response, 41% had a partial response, 3% had stable disease. For MM, 6% of patients had a pre-existing history of VTE, 2% had a history of ATE, 19% had a BMI ≥30, 96% had a recent procedure, 11% had an ICU stay and 19% had an infection. Seventeen percent had neurotoxicity, and 85% had CRS. Thirty-two percent of patients with NHL and 48% with MM received pharmacologic VTE prophylaxis while undergoing CAR-T. For those who did not receive VTE prophylaxis, thrombocytopenia was the reason for holding prophylaxis, which occurred in 51% and 50% of NHL and MM patients, respectively. In the 60 days post-CAR-T, 4 (11%) patients with NHL were diagnosed with VTE-3 pulmonary embolism (PE) and 1 lower extremity deep vein thrombosis (DVT) associated with a previously placed inferior vena cava filter. Four (7%) patients with MM were diagnosed with VTE-1 PE and 3 upper extremity DVTs associated with CVCs. Five out of these 8 (63%) patients had symptomatic VTE, while the remainder were incidental on PETCT. Mean time from CAR-T infusion to VTE diagnosis was 20 days (range 6-39 days). There were no documented ATEs. Six out of 8 (75%) were treated with therapeutic anticoagulation. Of those who were anticoagulated, 4 patients received direct oral anticoagulants and 2 received low-molecular-weight-heparin. Duration was 3 months in 3 patients, 11 days in 1, 150 days in 1, and indefinitely in 1 with atrial fibrillation. Among all 8 patients with VTE, there were no bleeding events or recurrent thromboses regardless of whether or not they received anticoagulation. Discussion: In this cohort of patients with R/R NHL or MM who received either CD19- or BCMA-directed therapies, almost 1 in 10 developed VTE in the 60 days post-CAR-T. This occurred in the context of a high prevalence of risk factors for thrombosis and low rates of pharmacologic prophylaxis. Among those who developed VTE, the majority were treated with therapeutic anticoagulation for at least 3 months, without documented bleeding or recurrent VTE. Our findings provide crucial information on a common complication that can inform patients, clinicians and researchers and should be expanded upon in larger, prospective studies to identify optimal preventive and therapeutic strategies. Disclosures Fakhri: University of California San Francisco: Current Employment. Andreadis:Jazz Pharmaceuticals: Honoraria; Karyopharm: Honoraria; Incyte: Consultancy; Merck: Research Funding; Gilead/Kite: Consultancy; Novartis: Research Funding; BMS/Celgene/Juno: Honoraria, Research Funding; Genentech: Consultancy, Current equity holder in publicly-traded company. Wong:Janssen: Research Funding; Amgen: Consultancy; Roche: Research Funding; Fortis: Research Funding; Sanofi: Membership on an entity's Board of Directors or advisory committees; Bristol Myers Squibb: Research Funding; GSK: Research Funding. Shah:BMS, Janssen, Bluebird Bio, Sutro Biopharma, Teneobio, Poseida, Nektar: Research Funding; GSK, Amgen, Indapta Therapeutics, Sanofi, BMS, CareDx, Kite, Karyopharm: Consultancy.