ABSTRACT
Background: The ZUMA-1 safety management Cohort 6 (N=40), which evaluated whether prophylactic corticosteroids and earlier corticosteroids and/or tocilizumab could improve safety outcomes, demonstrated an improved safety profile (no Grade >=3 cytokine release syndrome [CRS];15% Grade >=3 neurologic events [NEs]) vs pivotal Cohorts 1+2, without compromising response rate or durability (95% ORR, 80% CR rate, and 53% ongoing response rate with >=1 y of follow-up;Oluwole, et al. ASH 2021. 2832). Here, 2-y updated outcomes are reported. Method(s): Eligible pts with R/R LBCL underwent leukapheresis (followed by optional bridging therapy) and conditioning chemotherapy, then a single axi-cel infusion. Pts received corticosteroid prophylaxis (once-daily oral dexamethasone 10 mg on Days 0 [before axi-cel], 1, and 2) and earlier corticosteroids and/or tocilizumab for CRS and NE management vs Cohorts 1+2 (Oluwole, et al. Br J Haematol. 2021). The primary endpoints were incidence and severity of CRS and NEs. Secondary endpoints included ORR (investigator-assessed), duration of response (DOR), progression-free survival (PFS), overall survival (OS), and chimeric antigen receptor (CAR) T-cell levels in blood. Result(s): As of December 16, 2021, the median follow-up time for the 40 treated pts was 26.9 mo. Since the 1-y analysis, no new CRS events were reported (no pts had Grade >=3 CRS to date). The incidence of Grade >=3 NEs increased from 15% to 18%between the 1-y and 2-y analyses. Two new NEs occurred in 2 pts: 1 pt had Grade 2 dementia (onset on Day 685 and ongoing at time of data cutoff;not related to axi-cel) and 1 had Grade 5 axi-cel-related leukoencephalopathy. Since the 1-y analysis, 6 new infections were reported (Grades 1, 2, and 5 COVID-19 [n=1 each], Grade 3 Pneumocystis jirovecii pneumonia [n=1], Grade 3 unknown infectious episode with inflammatory syndrome [n=1], and Grade 2 herpes zoster [n=1]). In total, 8 deaths occurred since the 1-y analysis (progressive disease [n=5], leukoencephalopathy [n=1], and COVID-19 [n=2]). The ORR was 95% (80% CR), which was unchanged from the 1-y analysis. Median DOR and PFS were since reached (25.9 mo [95% CI, 7.8-not estimable] and 26.8 mo [95% CI, 8.7-not estimable], respectively). Median OS was still not reached. Kaplan- Meier estimates of the 2-y DOR, PFS, and OS rates were 53%, 53%, and 62%, respectively. Of 18 pts (45%) in ongoing response at data cutoff, all achieved CR as the best response. By Month 24, 14/20 pts with evaluable samples (70%) had detectable CAR T cells (vs 23/36 pts [64%] in Cohorts 1+2). Conclusion(s): With 2 y of follow-up, the ZUMA-1 Cohort 6 toxicity management strategy continued to demonstrate an improved long-term safety profile of axi-cel in pts with R/R LBCL. Further, responses remained high, durable, and similar to those observed in Cohorts 1+2 (Locke, et al. Lancet Oncol. 2019).Copyright © 2023 American Society for Transplantation and Cellular Therapy
ABSTRACT
G protein-coupled receptor family C group 5 member D (GPRC5D) has limited expression in healthy human tissue but is highly expressed in malignant plasma cells, making it a promising target for immunotherapy approaches for MM. Talquetamab (JNJ-64407564) is a first-in-class bispecific antibody that binds to both GPRC5D and CD3 receptors to redirect T cells to kill MM cells. Updated and new results of talquetamab at the recommended phase 2 doses (RP2Ds) are reported (NCT03399799). Eligible patients had RRMM or were intolerant to standard therapies. Patients who were previously treated with B-cell maturation antigen (BCMA)-directed therapies were eligible. This analysis focuses on patients who received talquetamab subcutaneously (SC;range: 5.0-800 μg/kg) weekly (QW) or biweekly (Q2W) with step-up dosing. The primary objectives were to identify the RP2D (part 1) and assess talquetamab safety and tolerability at the RP2Ds (part 2). Adverse events (AEs) were graded by CTCAE v4.03;cytokine release syndrome (CRS) was graded per Lee et al 2014 criteria. Responses were investigator-assessed per IMWG criteria. As of July 19, 2021, 95 patients had received SC talquetamab. The original RP2D was 405 μg/kg SC talquetamab QW with step-up doses, and a second RP2D of 800 μg/kg SC talquetamab Q2W with step-up doses was also identified. 30 patients received 405 μg/kg QW (median 61.5 years [range 46-80];63% male;100% triple-class exposed;80% penta-drug exposed;77% triple-class refractory, 20% penta-drug refractory;30% prior BCMA-directed therapy;median follow-up [mF/U]: 7.5 mo [range 0.9-15.2]). 23 patients received 800 μg/kg Q2W (median 60.0 years [range 47-84];48% male;96% triple-class exposed;70% penta-drug exposed;65% triple-class refractory, 22% penta-drug refractory;17% prior BCMA-directed therapy;mF/U: 3.7 mo [range 0.0-12.0]). No treatment discontinuations due to AEs were reported at either RP2Ds. Most common AEs at the 405 μg/kg QW were CRS (73%;1 grade 3 CRS), neutropenia (67%;grade 3/4: 60%), and dysgeusia (60%;grade 2: 29%). Skin-related AEs occurred in 77% of patients and were all grade 1/2 (nail disorders: 30%). Infections occurred in 37% of patients (1 grade 3 COVID-19 pneumonia). Most common AEs at 800 μg/kg Q2W were CRS (78%;all grade 1/2), dry mouth (44%;all grade 1/2), and neutropenia (44%;grade 3/4: 35%). Skin-related AEs occurred in 65% of patients with grade 3 events in 13% (nail disorders: 17%). Infections occurred in 13% of patients (1 grade 3 pneumococcal sepsis). In 30 response-evaluable patients treated at 405 μg/kg QW, the overall response rate (ORR) was 70% (very good partial response or better [≥VGPR]: 57%). In 17 response-evaluable patients treated at 800 μg/ kg Q2W, the ORR was 71% (≥VGPR: 53%). Responses were durable and deepened over time with both RP2Ds (Figure). Median duration of response (DOR) was not reached at either RP2D;6-month DOR rate was 67% (95% CI: 41-84) at 405 μg/kg QW. Serum trough levels of talquetamab were comparable at both RP2Ds. Pharmacodynamic data at both RP2Ds showed peripheral T cell activation and induction of cytokines. SC talquetamab is well tolerated and highly effective at both RP2Ds. Preliminary data suggest that less frequent, higher doses of SC talquetamab do not negatively impact the safety profile. Further evaluation of talquetamab as monotherapy (phase 2;NCT04634552) and in combination with other therapies in patients with RRMM is underway. (Figure Presented) .
ABSTRACT
Introduction: Despite recent advances in treatment, patients with multiple myeloma (MM) continue to relapse. G protein-coupled receptor family C group 5 member D (GPRC5D) is a promising target for immunotherapy in patients with MM due to its high expression in malignant plasma cells and limited expression in normal human tissue;unlike other antigens targeted by MM therapies, there is no indication that GPRC5D sheds into the periphery. Talquetamab (JNJ-64407564) is a first-in-class bispecific IgG4 antibody that redirects T cells to kill MM cells by binding to both GPRC5D and CD3 receptors. Here we report updated and new results of talquetamab at the recommended phase 2 doses (RP2Ds) from a phase 1 trial in relapsed/refractory MM (RRMM;NCT03399799). Methods: Eligible patients with MM had relapsed or refractory disease or were intolerant to standard therapies;patients previously treated with B-cell maturation antigen (BCMA)-directed therapies were eligible. This analysis focuses on patients who received talquetamab subcutaneously (SC;range 5.0-800 µg/kg) weekly or biweekly. Step-up dosing was used as a patient management strategy to minimize the severity of cytokine release syndrome (CRS). The primary objectives were to identify the RP2D (part 1) and assess talquetamab safety and tolerability at the RP2Ds (part 2). Adverse events (AEs) were graded by CTCAE v4.03 with CRS events graded per Lee et al 2014 criteria. Responses were investigator-assessed per International Myeloma Working Group criteria. Results: As of July 19, 2021, 95 patients have received SC talquetamab. The RP2D was originally identified as a weekly SC dose of 405 µg/kg talquetamab with step-up doses. However, alternative dosing schedules that require less frequent administration continue to be investigated. A biweekly RP2D was also identified as an SC dose of 800 µg/kg talquetamab with step-up doses. 30 patients received the 405 µg/kg weekly dosing schedule (median age: 61.5 years [range 46-80];63% male;100% triple-class exposed;80% penta-drug exposed;77% triple-class refractory, 20% penta-drug refractory;30% prior BCMA-directed therapy;median follow-up: 7.5 mo [range 0.9-15.2]). 23 patients received the 800 µg/kg biweekly dosing schedule (median age: 60.0 years [range 47-84];48% male;96% triple-class exposed;70% penta-drug exposed;65% triple-class refractory, 22% penta-drug refractory;17% prior BCMA-directed therapy;median follow-up 3.7 mo [range 0.0-12.0]). There were no treatment discontinuations due to AEs at either of the RP2Ds. The most common AEs at the 405 µg/kg weekly dose were CRS (73%;1 patient had grade 3 CRS), neutropenia (67%;grade 3/4: 60%), and dysgeusia (60%;grade 2: 29%);skin-related AEs occurred in 77% (all grade 1/2;nail disorders: 30%) of patients, and infections occurred in 37% of patients (1 patient had grade 3 COVID-19 pneumonia). The most common AEs at the 800 µg/kg biweekly dose were CRS (78%;all grade 1/2), dry mouth (44%;all grade 1/2), and neutropenia (44%;grade 3/4: 35%);skin-related AEs occurred in 65% of patients (grade 3: 13%;nail disorders: 17%) and infections occurred in 13% of patients (1 patient had grade 3 pneumococcal sepsis). In 30 response-evaluable patients treated with the 405 µg/kg weekly dose, the overall response rate (ORR) was 70% (very good partial response or better [≥VGPR] rate: 57%). In 17 response-evaluable patients treated with the 800 µg/kg biweekly dose, the ORR was 71% (≥VGPR rate: 53%). Responses were durable and deepened over time in both cohorts (Figure). Median duration of response (DOR) was not reached at either RP2D;the 6-month DOR rate for patients who received the 405 µg/kg weekly dose was 67% [95% CI: 41-84]. Serum trough levels of talquetamab were comparable at both RP2Ds. Consistent with the mechanism of action for talquetamab, pharmacodynamic data from cohorts treated at both dose levels showed peripheral T-cell activation and induction of cytokines. Conclusions: These findings indicate that SC talquetamab is well tolerated and highly effective at both RP2Ds. Preliminary data from the 800 µg/kg biweekly cohorts indicate that less frequent, higher doses of SC talquetamab do not have a negative impact on the previously described safety profile. Further investigation of talquetamab as monotherapy (phase 2;NCT04634552) and in combination with other therapies in patients with RRMM is underway. [Formula presented] Disclosures: Krishnan: MAGENTA: Consultancy;BMS: Consultancy, Current equity holder in publicly-traded company, Speakers Bureau;JANSSEN: Consultancy, Research Funding;City of Hope Cancer Center: Current Employment;REGENERON: Consultancy;SANOFI: Consultancy;GSK: Consultancy;Amgen: Speakers Bureau. Minnema: Celgene: Other: Travel expenses;Alnylam: Consultancy;Cilag: Consultancy;BMS: Consultancy;Janssen: Consultancy;Kite/Gilead: Consultancy. Berdeja: Lilly, Novartis: Research Funding;Abbvie, Acetylon, Amgen: Research Funding;Celularity, CRISPR Therapeutics: Research Funding;EMD Sorono, Genentech: Research Funding;Poseida, Sanofi, Teva: Research Funding;Bluebird bio, BMS, Celgene, CRISPR Therapeutics, Janssen, Kite Pharma, Legend Biotech, SecuraBio, Takeda: Consultancy;GSK, Ichnos Sciences, Incyte: Research Funding. Oriol: Sanofi: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees;Karyopharm: Consultancy, Membership on an entity's Board of Directors or advisory committees;Oncopeptides: Consultancy, 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;BMS/Celgene: 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. van de Donk: Roche: Consultancy;Takeda: Consultancy;Cellectis: Research Funding;Amgen: Consultancy, Research Funding;Janssen: Consultancy, Research Funding;BMS/Celgene: Consultancy, Honoraria;Novartis /bayer/servier: Consultancy. Rodriguez-Otero: Clínica Universidad de Navarra: Current Employment;Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees;Celgene-BMS: 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;Pfizer: Consultancy;Sanofi: 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;Amgen: Honoraria;Regeneron: Honoraria. Askari: Janssen: Research Funding. Mateos: Sanofi: Honoraria, Membership on an entity's Board of Directors or advisory committees;Sea-Gen: Honoraria, Membership on an entity's Board of Directors or advisory committees;Pfizer: Honoraria, Membership on an entity's Board of Directors or advisory committees;Regeneron: Honoraria, Membership on an entity's Board of Directors or advisory committees;Amgen: 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;Celgene - Bristol Myers Squibb: 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;Adaptive Biotechnologies: Honoraria, Membership on an entity's Board of Directors or advisory committees;Oncopeptides: Honoraria;Bluebird bio: Honoraria;AbbVie: Honoraria;GSK: Honoraria;Oncopeptides: Honoraria, Membership on an entity's Board of Directors or advisory committees;Roche: Honoraria, Membership on an entity's Board of Directors or advisory committees. Costa: BMS: Consultancy, Honoraria, Research Funding;Janssen: Consultancy, Honoraria, Research Funding;Amgen: Consultancy, Honoraria, Research Funding, Speakers Bureau;Karyopharm: Consultancy, Honoraria;Pfizer: Consultancy, Honoraria;Sanofi: Consultancy, Honoraria, Speakers Burea . Verona: Janssen: Current Employment. Ma: Janssen: Current Employment, Current holder of individual stocks in a privately-held company. Girgis: Janssen: Current Employment, Current holder of individual stocks in a privately-held company. Yang: Janssen: Current Employment. Hilder: Janssen: Current Employment, Current holder of individual stocks in a privately-held company. Russell: Janssen: Ended employment in the past 24 months. Goldberg: Janssen: Current Employment, Current holder of individual stocks in a privately-held company. Chari: Shattuck Labs: 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;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;BMS/Celgene: Consultancy, 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;Takeda: Consultancy, Research Funding;Amgen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding;Pharmacyclics: Research Funding;Secura Bio: Consultancy, Membership on an entity's Board of Directors or advisory committees;Oncopeptides: 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;GlaxoSmithKline: Consultancy, Membership on an entity's Board of Directors or advisory committees;Novartis: Consultancy, Research Funding;Genentech: Consultancy, Membership on an entity's Board of Directors or advisorycommittees;Janssen Oncology: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding.
ABSTRACT
Introduction: Despite recent advances, MM remains incurable and new therapeutic options are needed, particularly for pts with RRMM. IBER is a novel, potent oral cereblon E3 ligase modulator (CELMoD ®) compound with enhanced tumoricidal and immune-stimulatory effects compared with immunomodulatory (IMiD ®) agents. Preclinically, IBER demonstrated marked synergy with DEX and with other standard myeloma treatments. CC-220-MM-001 (NCT02773030) is an ongoing phase 1/2 study evaluating IBER with different treatment combinations in independent cohorts of pts with RRMM;in phase 1, the recommended phase 2 dose of IBER, when given in combination with DEX, was determined at 1.6 mg (Lonial S, et al. Blood 2019;134[suppl 1]:3119). Here we report results from the dose expansion of IBER + DEX in pts with heavily pretreated, triple-class exposed (including ≥ 1 IMiD agent, ≥ 1 proteasome inhibitor [PI], and ≥ 1 anti-CD38 monoclonal antibody [mAb]) RRMM. Methods: Eligible pts had RRMM;had received ≥ 3 prior lines of therapy, including lenalidomide (LEN), pomalidomide (POM), a PI, a glucocorticoid, and an anti-CD38 mAb;had experienced disease progression within 60 days of last myeloma therapy;and were refractory to an IMiD agent, a PI, a glucocorticoid, and an anti-CD38 mAb. Pts with central nervous system involvement were not eligible. Pts who had received prior anti-BCMA therapy were excluded, but included in a supportive cohort for safety and preliminary efficacy assessment. IBER (1.6 mg) was given orally on days (D) 1-21, in combination with DEX (40 mg;20 mg if > 75 years of age) on D1, 8, 15, and 22 of each 28-day cycle. Thrombo-embolism prophylaxis was mandatory for all pts. Primary objective was to determine efficacy expressed as overall response rate (ORR). Secondary endpoints included additional efficacy and safety assessments. Exploratory endpoints included evaluation of health-related quality of life (HRQoL). Results: As of June 2, 2021, 107 pts had received IBER + DEX. Median age was 64 (44-83) years;median time since initial diagnosis was 6.9 (1.6-24.5) years. Extramedullary plasmacytomas were present in 25.2% of pts;29.9% of pts had high-risk cytogenetics. Median number of prior regimens was 6 (3-23). All pts were triple-class exposed;prior therapies included autologous stem cell transplantation (78.5%), PIs (100%), IMiD agents (LEN [100%] and POM [100%]), and anti-CD38 mAbs (100%);99.1% of pts were refractory to last myeloma regimen and 97.2% of pts were triple-class refractory. Median follow-up was 7.69 (0.5-17.5) months, with a median number of 4 (1-17) cycles received and 13 (12.1%) pts continuing treatment. Main reason for discontinuation was progressive disease (69.2%). ORR was 26.2%, with 1 (0.9%) stringent complete response, 8 (7.5%) very good partial responses, and 19 (17.8%) partial responses (Table);the clinical benefit rate (≥ minimal response) was 36.4% and disease control rate (≥ stable disease) was 79.4%. Median duration of response was 7.0 (4.5-11.3) months (Table), median progression-free survival was 3.0 (2.8-3.7) months, and median overall survival was 11.2 (9.0-not reached) months. Similar response rates were observed among a cohort of pts also exposed to BCMA therapies (N = 24, Table). Grade (Gr) 3-4 treatment-emergent adverse events (TEAEs) were reported in 88 (82.2%) pts. Most frequent (≥ 20% pts) hematologic Gr 3-4 TEAEs were neutropenia (44.9%;and 4.7% febrile neutropenia), anemia (28.0%), thrombocytopenia (21.5%), and leukopenia (20.6%). Gr 3-4 infections were reported in 27.1% of pts;Gr 3-4 pneumonia and COVID-19 occurred in 10.3% and 4.7% of pts, respectively. Occurrence of other Gr 3-4 non-hematologic TEAEs was generally low, including gastrointestinal disorders (5.6%), fatigue (2.8%), rash (1.9%). Fifty-six (52.3%) pts and 20 (18.7%) had IBER dose interruptions and reductions due to TEAEs, respectively. Five (4.7%) pts discontinued due to TEAEs. No pt discontinued IBER due to neutropenia. Overall, HRQoL was maintained in these pts. Conclusions: IBER + DEX demonst ated promising efficacy in pts with heavily pretreated, triple-class exposed and refractory RRMM, as well as in pts who had previously received anti-BCMA therapy;this combination was generally well tolerated and TEAEs were manageable with dose reductions and interruptions. These results support the further development of IBER in MM, including phase 3 trials in combination regimens. [Formula presented] Disclosures: Lonial: Abbvie: Consultancy, Honoraria;AMGEN: Consultancy, Honoraria;Takeda: Consultancy, Honoraria, Research Funding;GlaxoSmithKline: Consultancy, Honoraria, Research Funding;TG Therapeutics: Membership on an entity's Board of Directors or advisory committees;Merck: Honoraria;BMS/Celgene: Consultancy, Honoraria, Research Funding;Janssen: Consultancy, Honoraria, Research Funding. Popat: GlaxoSmithKline: Consultancy, Honoraria, Research Funding;Abbvie, Takeda, Janssen, and Celgene: Consultancy;Takeda: Honoraria, Other: TRAVEL, ACCOMMODATIONS, EXPENSES;AbbVie, BMS, Janssen, Oncopeptides, and Amgen: Honoraria;Janssen and BMS: Other: travel expenses. Hulin: Sanofi: Honoraria;Celgene/BMS: Honoraria;Janssen: Honoraria;Takeda: Honoraria;abbvie: Honoraria. Jagannath: Legend Biotech: Consultancy;Bristol Myers Squibb: Consultancy;Karyopharm Therapeutics: Consultancy;Janssen Pharmaceuticals: Consultancy;Sanofi: Consultancy;Takeda: Consultancy. Oriol: Oncopeptides: Consultancy, 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;GSK: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees;Karyopharm: Consultancy, 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;Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees. Richardson: Karyopharm: Consultancy, Research Funding;Regeneron: Consultancy;AbbVie: Consultancy;Celgene/BMS: Consultancy, Research Funding;Oncopeptides: Consultancy, Research Funding;GlaxoSmithKline: Consultancy;Protocol Intelligence: Consultancy;Janssen: Consultancy;Secura Bio: Consultancy;Takeda: Consultancy, Research Funding;Sanofi: Consultancy;AstraZeneca: Consultancy;Jazz Pharmaceuticals: Consultancy, Research Funding. Weisel: Adaptive Biotechnologies: 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;Roche: Honoraria;Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding;Celgene: 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;Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding;GSK: 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;Sanofi: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding;Bristol Myers Squibb: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding;Abbvie: Consultancy;Novartis: Honoraria;Pfizer: Honoraria. Minnema: Cilag: Consultancy;Janssen: Consultancy;Alnylam: Consultancy;Celgene: Other: Travel expenses;Kite/Gilead: Consultancy;BMS: Consultancy. Badros: J&J: Research Funding;Janssen: Research Funding;BMS: Research Funding;GlaxoSmithKline: Research Funding. Knop: BMS/Celgene: Consultancy, Honoraria, Research Funding;Amgen: Research Funding;Janssen: Consultancy;Oncopeptides: Consultancy;Pfizer: Consultancy;Sanofi: Consultanc . Stadtmauer: Janssen: Consultancy, Honoraria;Takeda: Consultancy, Honoraria;Abbvie: Consultancy, Honoraria;Amgen: Consultancy, Honoraria;Bristol Myers Squibb: Consultancy, Honoraria, Research Funding. Chen: Bristol Myers Squibb: Current Employment. Nguyen: Bristol Myers Squibb: Current Employment, Current equity holder in publicly-traded company. Amin: Bristol Myers Squibb: Current Employment. Kueenburg: Celgene a BMS company: Current Employment. Peluso: Celgene, a Bristol-Myers Squibb Company: Current Employment. van de Donk: BMS/Celgene: Consultancy, Honoraria;Janssen: Consultancy, Research Funding;Amgen: Consultancy, Research Funding;Cellectis: Research Funding;Takeda: Consultancy;Roche: Consultancy;Novartis /bayer/servier: Consultancy.