Abstract: Introduction: CANDOR is a multicenter, phase 3, randomized study of adult patients with relapsed or refractory multiple myeloma (RRMM) previously treated with 1-3 prior lines of therapy (NCT03158688). 466 patients received carfilzomib, dexamethasone, and daratumumab (KdD) or carfilzomib and dexamethasone (Kd) in 2:1 randomization (KdD: 312; Kd: 154). Based on the primary endpoint, KdD demonstrated superior progression-free survival (PFS) vs Kd (hazard ratio [HR], 0.63 [95% CI, 0.46-0.85] ; P=0.0014). Deep responses and minimal residual disease (MRD) negativity have been associated with improved PFS for patients with RRMM. Herein, we present an analysis of MRD results from CANDOR. Methods: Details of the dose and schedule were previously reported (Dimopoulos et al., Lancet 2020). The rate of patients with confirmed CR which were MRD negative (MRD[-]CR) in bone marrow aspirate at 12 months (± 4 weeks) measured by next-generation sequencing (NGS; threshold, 1 tumor cell/10-5 white blood cells) was a prespecified key secondary endpoint. Exploratory analyses included MRD[-] CR at increasing sensitivity (10-4, 10-5, 10-6) and best overall response MRD[-] status at any time point. All reported responses were by Independent Review Committee and were analyzed for the Intent-to-Treat population. MRD[-] status is at & lt;10-5 unless otherwise specified. Results: The best overall MRD[-]CR rate at any time was 13.8% vs 3.2% in the KdD vs Kd arm (Odds ratio [OR] , 4.95; P & lt;0.0001) and the MRD[-] rate regardless of overall response status was 22.8% vs 5.8% (OR, 5.15; P & lt;0.0001). At the 12-month landmark, the MRD[-]CR rate was 12.5% vs 1.3% in the KdD vs Kd arm (OR, 11.3; P & lt;0.0001) and the MRD[-] rate was 17.6% vs 3.9% (OR, 5.76; P & lt;0.0001) with the proportion of patients with MRD[-]VGPR being 4.2% vs 2.6%, respectively. The MRD[-] CR rates at the 12-month landmark for KdD vs Kd were consistent across clinically relevant subgroups (Table). At the 12-month landmark, KdD treatment resulted in a greater proportion of CR rates (26.9% vs 9.7%) and deeper MRD responses than Kd. Among patients in CR, the depth of response as measured by NGS MRD level at the 12-month landmark was deeper for KdD relative to Kd: cutoff of & gt;10-4, 36.9% vs 73.3%; 10-4 to 10-5, 16.7% vs 13.3%; 10-5 to 10-6, 23.8% vs 13.3%; & lt;10-6, 22.6% vs 0% for KdD vs Kd, respectively (Figure). Similar to the results at the 12-month landmark, MRD responses independent of the landmark were deeper among patients in the KdD compared to the Kd arm. With median follow-up of 6 months from the 12-month landmark, no patient with MRD[-] CR response progressed or died. Additional post hoc analyses were conducted within patients randomized to KdD to explore prognostic characteristics for MRD[-]CR. Importantly, prior lenalidomide exposure did not meaningfully impact the MRD[-] CR rate at the 12-month landmark; 13.2% (25/189), 11.4% (14/123), and 13.1% (13/99) for naïve, exposed, and refractory subgroups, respectively. For prior bortezomib, the MRD[-]CR rates were 24% (6/25), 11.5% (33/287), and 6.8% (6/88) for naïve, exposed, and refractory subgroups, respectively. The rates of MRD[-] CR at the 12- month landmark within the KdD arm were consistent across subgroups: patients refractory to the last prior therapy (yes vs no, 10.9% vs 14.3%), number of prior regimens (1-2 vs 3 prior regimens; 13.2% vs 10.1%), prior transplant (yes vs no, 11.8% vs 13.7%), duration of first remission (≤2 vs & gt;2 years, 12.3% vs 13% and ≤1 vs & gt;1 year, 10.7% vs 13.4%), baseline creatinine clearance (≥15 to & lt;50, ≥50 to & lt;80, and ≥80 mL/min, 10.5%, 14.4%, and 11.9%, respectively), age (≤75 vs & gt;75 years, 12.9% vs 8.0%), or dose intensity ( & lt; vs ≥ median) for carfilzomib or daratumumab (10.5% vs 14.9% and 9.8% vs 15.6%, respectively). Data on cytogenetics will be included at the time of presentation. Conclusion: At the primary analysis, patients treated with KdD achieved significantly higher MRD[-]CR rates vs Kd at the 12-month landmark. Among patients with an MRD[-] CR, the depth of MRD was deeper with KdD vs Kd. With a median of 6 months follow-up, no patient with an MRD[-]CR has progressed; duration of response will be updated at time of presentation. Within the KdD arm, lenalidomide exposure or refractoriness did not diminish the MRD[-] CR rate. These findings support the efficacy of the KdD regimen as an effective treatment for RRMM, including patients who have become lenalidomide refractory. Disclosures Landgren: Adaptive: Consultancy, Honoraria; Amgen: Consultancy, Honoraria, Research Funding; Pfizer: Consultancy, Honoraria; Juno: Consultancy, Honoraria; Cellectis: Consultancy, Honoraria; BMS: Consultancy, Honoraria; Binding Site: Consultancy, Honoraria; Karyopharma: Research Funding; Merck: Other; Pfizer: Consultancy, Honoraria; Seattle Genetics: Research Funding; Juno: Consultancy, Honoraria; Glenmark: Consultancy, Honoraria, Research Funding; Cellectis: Consultancy, Honoraria; BMS: Consultancy, Honoraria; Takeda: Other: Independent Data Monitoring Committees for clinical trials, Research Funding; Binding Site: Consultancy, Honoraria; Karyopharma: Research Funding; Janssen: Consultancy, Honoraria, Other: Independent Data Monitoring Committees for clinical trials, Research Funding; Seattle Genetics: Research Funding; Celgene: Consultancy, Honoraria, Research Funding; Glenmark: Consultancy, Honoraria, Research Funding; Takeda: Other: Independent Data Monitoring Committees for clinical trials, Research Funding; Janssen: Consultancy, Honoraria, Other: Independent Data Monitoring Committees for clinical trials, Research Funding; Celgene: Consultancy, Honoraria, Research Funding; Merck: Other. Weisel:Roche: Consultancy, Honoraria; Amgen: Consultancy, Honoraria, Research Funding; Celgene: Consultancy, Honoraria, Research Funding; Janssen: Consultancy, Honoraria, Research Funding; Sanofi: Consultancy, Honoraria, Research Funding; Bristol-Myers Squibb: Consultancy, Honoraria; Adaptive: Consultancy, Honoraria; GlaxoSmithKline: Honoraria; Karyopharm: Consultancy, Honoraria; Takeda: Consultancy, Honoraria; Abbvie: Consultancy, Honoraria. Rosinol Dachs:Janssen: Honoraria; Celgene: Honoraria; Amgen: Honoraria; Takeda: Honoraria; Sanofi: Honoraria. Moreau:Sanofi: Consultancy, Honoraria; Amgen: Consultancy, Honoraria; Celgene/Bristol-Myers Squibb: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; Novartis: Honoraria; Takeda: Honoraria; Abbvie: Consultancy, Honoraria. Hajek:PharmaMar: Consultancy, Honoraria; Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Abbvie: Consultancy, Honoraria; Oncopeptides: Consultancy; Novartis: Consultancy, Research Funding; Janssen: Consultancy, Honoraria, Research Funding; Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; BMS: Consultancy, Honoraria, Research Funding; Celgene: Consultancy, Honoraria, Research Funding. Mollee:Janssen: Membership on an entity's Board of Directors or advisory committees, Research Funding; BMS/Celgene: Membership on an entity's Board of Directors or advisory committees; Amgen: Membership on an entity's Board of Directors or advisory committees; Takeda: Membership on an entity's Board of Directors or advisory committees; Pfizer: Membership on an entity's Board of Directors or advisory committees; Caelum: Membership on an entity's Board of Directors or advisory committees. Kim:Alexion Pharmaceuticals Inc.: Honoraria, Research Funding. Zhang:Amgen: Current Employment. Go:Amgen: Current Employment. Morris:Amgen: Current Employment. Usmani:Celgene: Other; Takeda: Consultancy, Honoraria, Other: Speaking Fees, Research Funding; Janssen: Consultancy, Honoraria, Other: Speaking Fees, Research Funding; SkylineDX: Consultancy, Research Funding; Seattle Genetics: Consultancy, Research Funding; Merck: Consultancy, Research Funding; Incyte: Research Funding; Pharmacyclics: Research Funding; Array Biopharma: Research Funding; GSK: Consultancy, Research Funding; Sanofi: Consultancy, Honoraria, Research Funding; Abbvie: Consultancy; BMS, Celgene: Consultancy, Honoraria, Other: Speaking Fees, Research Funding; Amgen: Consultancy, Honoraria, Other: Speaking Fees, Research Funding.

Abstract: Background: The advent of immunotherapy renewed the interest in immune monitoring to identify determinants of treatment response. Flow cytometry is widely adopted in immunotherapy-based clinical trials, but manual analysis of multiparameter files poses a challenge to capture full cellular diversity and to provide unbiased reporting in large datasets. Methods: Here, we developed a semi-automated pipeline named "FlowCT" which, starting from compensated data obtained with standardized protocols, allows simultaneous analyses of multiple files and automated cell clustering. FlowCT starts with quality control and data normalization followed by an analytical stage with clustering algorithms, dimensional reduction techniques and cluster identification based on antigen expression. Statistical tools are included for immediate analysis of results. Results: As proof-of-concept, we used FlowCT in three different datasets. First, we applied FlowCT to bone marrow (BM) samples from three multiple myeloma (MM) patients stained with 17-color flow cytometry, to determine the increment in the complexity of analyzing 8 and 17 markers, chosen to characterize T cells. Of note, a single combination of CD3, CD4, CD8, CD45RA, CD56, CCR7, PD1 and TIGIT, allowed the identification of 31 lymphocyte subsets using FlowCT, which increased to 39 different clusters with 17 markers and unveiled a novel population of CD3- CD56- CD8+ CD16+ lymphoid cells in the MM immune microenvironment. Secondly, we applied FlowCT to matched peripheral blood (PB) and BM samples from 10 patients with smoldering MM, to objectively assess if PB represents a good surrogate of T-cell distribution in the BM. Using an 8-color combination to characterize CD4 T cells, up to 26 different subsets were identified, including several CD4 T helper (Th) type subsets. Of note, their distribution within PB CD4 T cells was similar to that found in BM, except for CD4 T CXCR3+CCR4+ effector memory and Th17 central memory subsets that decreased in the BM tumor immune microenvironment. Thirdly, we analyzed 30 BM samples from 10 MM patients studied every year during maintenance therapy, monitored with CD4, CD8, CD25, CD45RA, CD127, CCR7, PD1, and TCRγδ to characterize T cells. FlowCT identified 29 different T-cell populations, including 9 CD4 subsets, 14 CD8 subsets, 4 Tγδ cell subsets and 2 distinct Treg subsets. Longitudinal, semi-automated and unbiased analysis unveiled a significant fluctuation of CD4 naïve and transitional memory cells during maintenance, as well as a significant decrease of CD8 CD127- effector memory and transitional effectors cells after 2 years of maintenance. Conclusions: Here, we presented FlowCT, a pipeline optimized for the analysis of large flow cytometry datasets that could be easily implemented by research laboratories to unveil full cellular diversity, singular patterns of antigen expression, and to provide unbiased reporting in large studies, like clinical trials. Disclosures Puig: Amgen: Consultancy, Honoraria; Janssen: Consultancy, Honoraria, Research Funding; Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; The Binding Site: Honoraria; Takeda: Consultancy, Honoraria. Borrello:WindMIL Therapeutics: Equity Ownership, Patents & Royalties, Research Funding; Aduro: Patents & Royalties: intellectual property on allogeneic MM GVAX; BMS: Consultancy; Celgene: Honoraria, Research Funding, Speakers Bureau. Rosinol Dachs:Janssen, Celgene, Amgen and Takeda: Honoraria. Mateos:Janssen, Celgene, Takeda, Amgen, GSK, Abbvie, EDO, Pharmar: Membership on an entity's Board of Directors or advisory committees; Janssen, Celgene, Takeda, Amgen, Adaptive: Honoraria; Amgen Inc, Janssen Biotech Inc: Other: Data and Monitoring Committee; Amgen Inc, Celgene Corporation, Janssen Biotech Inc, Takeda Oncology.: Speakers Bureau; AbbVie Inc, Amgen Inc, Celgene Corporation, Genentech, GlaxoSmithKline, Janssen Biotech Inc, Mundipharma EDO, PharmaMar, Roche Laboratories Inc, Takeda Oncology: Other: Advisory Committee. Lahuerta:Takeda, Amgen, Celgene and Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees. Bladé:Jansen, Celgene, Takeda, Amgen and Oncopeptides: Honoraria. San-Miguel:Amgen, Bristol-Myers Squibb, Celgene, Janssen, MSD, Novartis, Roche, Sanofi, and Takeda: Consultancy, Honoraria. Paiva:Celgene, Janssen, Sanofi and Takeda: Consultancy; Amgen, Bristol-Myers Squibb, Celgene, Janssen, Merck, Novartis, Roche and Sanofi: Honoraria, Membership on an entity's Board of Directors or advisory committees.

Abstract: In MM patients relapsing after MRD-negativity, the disease could reemerge from immature cells or from undetectable MRD. However, it remains unknown if immature cells have the same genetic background as MM plasma cells (PCs), as well as the amount of MRD that persists below the limit of detection (LOD) of next-generation techniques. To obtain further insight, we compared the biological landscape of MM PCs at diagnosis to that of CD34 progenitors, B cells and normal PCs isolated from patients with negative MRD by next-generation flow (NGF) after treatment. We performed whole-exome sequencing (WES, mean depth: 90x) with the 10XGenomics Exome Solution for low DNA-input as well as deep NGS of B-cell receptor immunoglobulin (BcR IG) gene rearrangements (mean, 69,975 sequences), in a total of 68 cell-samples isolated from the bone marrow (BM) of 7 MM patients with MRD-negativity by EuroFlow NGF after induction with VRD and auto-transplant (GEM2012MENOS65 trial). Patients with negative MRD were intentionally selected to avoid contamination with MM PCs during sorting of CD34 progenitors, B-cell precursors, mature B cells and normal PCs after induction and transplant. We investigated in these populations the presence of somatic mutations and clonotypic BcR Ig rearrangements detectable in MM PCs sorted at diagnosis, using peripheral blood T cells as germline control. We also performed WES in matched diagnostic MM PCs and MRD cells persisting after VRD induction in 14 cases as control. In another 6 patients with untreated MM, we performed single-cell RNA and BcR IG sequencing (scRNA/BcRIGseq) of total BM B cells and PCs (n=16,380) to investigate before treatment, if the clonotypic BcR IG sequence of MM PCs was detectable in other B cell stages defined by their molecular phenotype. We used multidimensional flow cytometry (MFC) to investigate the frequency of B cell clonality in BM samples from a larger series of 195 newly-diagnosed MM patients, prospectively enrolled in the GEM-CLARIDEX trial. Somatic mutations present in diagnostic MM PCs were detectable in the lymphopoiesis of 5/7 patients achieving MRD-negativity after treatment. In one case, out of 55 mutations present in diagnostic MM PCs, a single mutation in PCSK1N (VAF: 0.30) was detectable in normal PCs. In the other four patients, a total of 85 mutations were present in MM PCs and up to 10 (median VAF, 0.16) were found all the way from CD34 progenitors into B-cell precursors, mature B cells and normal PCs, but not in T cells. Of note, most mutations were reproducibly detected in each cell type after induction and after transplant. All somatic mutations shared by MM PCs and normal cells were non-recurrent, and genes recurrently mutated in MM (eg. ACTG1, ATM, DIS3, FAM46C, KRAS, LTB, MAX, TRAF3) were found in MM PCs but never in normal cells. Copy number alterations (CNA) were found only in MM PCs. By contrast, up to 513/827 (62%) mutations and 48/67 (72%) CNA were detectable in matched diagnostic MM PCs and persistent MRD cells, indicating that the few somatic variants present in normal cells were unlikely related to contaminating MRD below NGF's LOD. Accordingly, MM clonotypic BcR IG rearrangements were detectable in normal PCs (4/7patients) and in immature B cells (5/7 patients) but at much lower frequencies (mean of 0.02% in both). Of note, 9 additional clonotypes (mean 8.4%) were found in MM PCs of 5/7 patients (range, 1-3). scRNR/BcRIGseq unveiled that clonotypic cells were confined mostly but not entirely within PC clusters, and that in 1 patient another clonotype was detectable in mature B cells. Accordingly, using MFC we found in a larger series that 25/195 (13%) of newly-diagnosed MM patients display B-cell clonality (median of 0.7% BM clonal B cells, range 0.02%-6.3%). In conclusion, we show for the first time that MM patients bear somatic mutations in CD34 progenitors that specifically differentiate into the B cell lineage, likely before the disease onset. Because diagnostic, MRD (and relapse) MM PCs display great genetic similarity, these results suggest that undetectable MRD & lt;10-6 rather than normal cells with a few non-recurrent mutations are responsible for relapses after MRD-negativity. This study also challenges our understanding of myelomagenesis and clonal heterogeneity, and proposes that mutated lymphopoiesis may increase risk of developing B cell and PC oligoclonality, which precedes secondary driver mutations or CNA leading to the expansion of MM PCs. Disclosures Puig: Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Takeda, Amgen: Consultancy, Honoraria; The Binding Site: Honoraria; Janssen: Consultancy, Honoraria, Research Funding. Martinez-Lopez:BMS: Honoraria, Other: Advisory boards; Janssen: Honoraria, Other: Advisory boards and Non-Financial Support ; Amgen: Honoraria, Other: Non-Financial Support ; Celgene: Honoraria, Other: Advisory boards and Non-Financial Support ; Incyte: Honoraria, Other: Advisory boards; Novartis: Honoraria, Other: Advisory boards; VIVIA Biotech: Honoraria; F. Hoffmann-La Roche Ltd: Honoraria. Lahuerta:Takeda, Amgen, Celgene and Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees. Rosinol Dachs:Janssen, Celgene, Amgen and Takeda: Honoraria. Bladé:Jansen, Celgene, Takeda, Amgen and Oncopeptides: Honoraria. Mateos:EDO: Membership on an entity's Board of Directors or advisory committees; Abbvie: Membership on an entity's Board of Directors or advisory committees; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees; GSK: Membership on an entity's Board of Directors or advisory committees; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Adaptive: Honoraria; Takeda: 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; Pharmamar: Membership on an entity's Board of Directors or advisory committees. San-Miguel:Amgen, Bristol-Myers Squibb, Celgene, Janssen, MSD, Novartis, Roche, Sanofi, and Takeda: Consultancy, Honoraria. Paiva:Amgen, Bristol-Myers Squibb, Celgene, Janssen, Merck, Novartis, Roche, and Sanofi; unrestricted grants from Celgene, EngMab, Sanofi, and Takeda; and consultancy for Celgene, Janssen, and Sanofi: Consultancy, Honoraria, Research Funding, Speakers Bureau.

Abstract: BACKGROUND Triplet regimens bortezomib + lenalidomide + dexamethasone (VRD) and bortezomib + thalidomide + dexamethasone (VTD) are recommended in both European and US guidelines for the treatment (Tx) of transplant-eligible (TE) patients (pts) with newly diagnosed multiple myeloma (NDMM). To date, there are no randomized controlled trials (RCTs) directly comparing them. Therefore, this integrated analysis evaluated VRD vs VTD in TE pts with NDMM. METHODS Published literature was searched for prospective, phase 3 RCTs evaluating VRD or VTD induction (every 3 or 4 weeks) in TE NDMM before autologous stem cell transplant (ASCT). Studies were included if they met pre-defined eligibility criteria, which included having access to pt-level data. The primary objective was noninferiority of the primary endpoint (≥ very good partial response [VGPR] rate post induction. Secondary endpoints included ≥ VGPR rate during induction and post ASCT, and safety. Progression-free survival (PFS) and minimal residual disease (MRD) negativity were exploratory endpoints. Statistical methods for efficacy analyses were based on propensity score (PS), and pts with missing baseline values for the variables used for the PS analyses were excluded. The Cochran-Mantel-Haenszel test, stratified on the stratum based on the quintiles of the PS, was used to estimate the difference of ≥ VGPR rate and 95% CI. RESULTS Four studies met the eligibility criteria: VRD, PETHEMA GEM (GEM)2012 and IFM 2009; VTD, GEM2005 and IFM 2013-04. GEM2005 and GEM2012 were the main studies, as they had a symmetrical design of the induction regimens (six 4-week cycles followed by ASCT). IFM studies were considered supportive since they had a variable number of cycles (3 VRD cycles before ASCT vs 8 VRD cycles in IFM 2009 and 4 VTD cycles before ASCT in IFM 2013-04). Thus, IFM analyses used the subgroup of pts from the VRD induction and consolidation arm of IFM 2009 to compare with the IFM 2013-04 VTD arm. No clinically meaningful differences in baseline characteristics were observed between the VRD and VTD PS-stratified cohorts of the GEM and IFM studies. The integrated analysis met its primary endpoint (noninferiority) and demonstrated a statistically significant and clinically relevant improvement of the ≥ VGPR rate after induction with VRD vs VTD (66.3% vs 51.2%; P = .00281; Figure) in the GEM studies. Non-inferiority results from the IFM studies supported those from GEM, with ≥ VGPR rate by 4 cycles (12 weeks) similar with VRD vs VTD (57.1% vs 56.5%). In the GEM studies, responses deepened during induction. Among the 378 VRD pts who started cycle 6, ≥ VGPR rate increased from 54.5% by 3 cycles of induction to 62.7% by 4 cycles, and to 70.1% by 6 cycles and post induction. Of the 111 VTD pts, these rates were 35.1%, 40.5%, and 55.9%, respectively. Analyses of ≥ VGPR rate post ASCT (74.4% vs 53.5%) and MRD negativity (10-4) rates post induction (46.7% vs 34.9%) and post ASCT (62.4% vs 47.3%) supported the benefit of VRD vs VTD. Safety was as previously reported for these studies. Peripheral neuropathy (PN) is a recognized event that can limit VRD and VTD Tx duration. In the GEM studies, subcutaneous (SC) vs intravenous (IV) administration of bortezomib (BORT) may have contributed to lower rates of PN (grouped term) with VRD vs VTD (grade 3/4, 5.5% vs 15.4%; grade ≥ 2, 20.7% vs 44.6%). Treatment-emergent adverse events (TEAEs) led to dose reduction and study or Tx discontinuation less frequently in the VRD vs VTD cohorts, respectively. In the IFM studies, TEAEs led to dose reduction more frequently and Tx discontinuation less frequently with VRD than with VTD. Grade 3/4 PN (grouped term) was 5.9% vs 15.4%, whereas grade ≥ 2 events were similar (30.3% vs 27.2%), which may reflect BORT administration in these IFM studies (IV for VRD vs SC for VTD, respectively). CONCLUSIONS Induction Tx with VRD had a significantly higher ≥ VGPR rate than VTD when 6 cycles of each Tx were compared in TE NDMM. Deepening responses and MRD negativity further support the benefit of VRD over VTD. TEAEs in the GEM and IFM studies were generally consistent with the known safety profiles of lenalidomide, BORT, thalidomide, and dexamethasone. The TEAEs with the VRD regimen were manageable, and the overall tolerability profile compared well with VTD, with lower rates of PN and TEAEs leading to discontinuation. The integrated analysis supports the favorable benefit-risk profile with VRD over VTD as induction Tx in TE pts with NDMM. Disclosures Rosinol Dachs: Janssen: Honoraria; Celgene: Honoraria; Amgen: Honoraria. Oriol:Amgen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Takeda: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Rios:Amgen, Celgene, Janssen, and Takeda: Consultancy. Hulin:Celgene: Honoraria, Research Funding; Janssen: Honoraria, Research Funding. Sureda:Merck: Consultancy, Honoraria; BMS: Consultancy, Honoraria; Takeda: Consultancy, Honoraria, Speakers Bureau; Roche: Honoraria; Sanofi: Honoraria. Mateos:Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Abbvie: Consultancy, Membership on an entity's Board of Directors or advisory committees; GSK: Consultancy, 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; GSK: Consultancy, 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; Takeda: 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. Macro:Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Financial support for congress; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Financial support for congress; Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Financial support for congress; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Financial support for congress. San-Miguel:Amgen: Consultancy; Brystol-Myers Squibb: Consultancy; Celgene: Consultancy; Janssen: Consultancy; MSD: Consultancy; Novartis: Consultancy; Takeda: Consultancy; Sanofi: Consultancy; Roche: Membership on an entity's Board of Directors or advisory committees. Belhadj:Janssen: Consultancy, Honoraria; Takeda: Consultancy, Honoraria; Amgen: Consultancy, Honoraria; Celgene: Consultancy, Honoraria. Lahuerta:Amgen: Honoraria; Janssen: Honoraria; Celgene: Honoraria. Chen:Celgene Corporation: Employment. Garelik:Celgene Corporation: Employment. Bladé:Celgene: Honoraria; Amgen: Honoraria; Janssen: Honoraria. Moreau:Janssen: 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; Amgen: 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; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees.