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Anti-CD38 monoclonal antibodies have consistently shown increased efficacy when added to standard of care for patients with multiple myeloma. We aimed to assess the efficacy of isatuximab in addition to lenalidomide, bortezomib, and dexamethasone in patients with newly diagnosed transplantation-eligible multiple myeloma.This open-label, multicentre, randomised, active-controlled, phase 3 trial was done at 67 academic and oncology practice centres in Germany. This study is ongoing and divided into two parts; herein, we report results from part 1. Eligible patients were aged 18-70 years; had a confirmed diagnosis of untreated multiple myeloma requiring systemic treatment and a WHO performance status of 0-2; and were eligible for induction therapy, high-dose melphalan and autologous haematopoietic stem-cell transplantation, and maintenance treatment. Patients were randomly assigned (1:1) to receive three 42-day cycles of induction therapy either with isatuximab plus lenalidomide, bortezomib, and dexamethasone (isatuximab group) or lenalidomide, bortezomib, and dexamethasone alone (control group) using a web-based system and permuted blocks. Patients in both groups received lenalidomide (25 mg orally on days 1-14 and 22-35), bortezomib (1·3 mg/mBetween Oct 23, 2018, and Sep 22, 2020, 660 patients were included in the ITT analysis (331 in the isatuximab group and 329 in the control group). 654 (99%) patients were White, two were African, one was Arabic, and three were Asian. 250 (38%) were women and 410 (62%) were men. The median age was 59 years (IQR 54-64). MRD negativity after induction therapy was reached in 166 (50%) patients in the isatuximab group versus 117 (36%) in the control group (OR 1·82 [95% CI 1·33-2·48]; p=0·00017). Median follow-up time from start to end of induction therapy was 125 days (IQR 125-131) versus 125 days (125-132). At least one grade 3 or 4 adverse event occurred in 208 (63%) of 330 patients versus 199 (61%) of 328 patients. Neutropenia of grade 3 or 4 occurred in 77 (23%) versus 23 (7%) patients and infections of grade 3 or 4 occurred in 40 (12%) versus 32 (10%) patients. Among 12 deaths during induction therapy, one death due to septic shock in the isatuximab group and four deaths (one cardiac decompensation, one hepatic and renal failure, one cardiac arrest, and one drug-induced enteritis) in the control group were considered treatment-related.Addition of isatuximab to lenalidomide, bortezomib, and dexamethasone for induction therapy improved rates of MRD negativity with no new safety signals in patients with newly diagnosed transplantation-eligible multiple myeloma.Sanofi and Bristol Myers Squibb (Celgene).

Supplementary Figure from Circulating Tumor and Immune Cells for Minimally Invasive Risk Stratification of Smoldering Multiple Myeloma

Supplementary Data from Circulating Tumor and Immune Cells for Minimally Invasive Risk Stratification of Smoldering Multiple Myeloma

Supplementary Table from Circulating Tumor and Immune Cells for Minimally Invasive Risk Stratification of Smoldering Multiple Myeloma

Purpose:Early intervention in smoldering multiple myeloma (SMM) requires optimal risk stratification to avoid under- and overtreatment. We hypothesized that replacing bone marrow (BM) plasma cells (PC) for circulating tumor cells (CTC), and adding immune biomarkers in peripheral blood (PB) for the identification of patients at risk of progression due to lost immune surveillance, could improve the International Myeloma Working Group 20/2/20 model.Experimental Design:We report the outcomes of 150 patients with SMM enrolled in the iMMunocell study, in which serial assessment of tumor and immune cells in PB was performed every 6 months for a period of 3 years since enrollment.Results:Patients with >0.015% versus ≤0.015% CTCs at baseline had a median time-to-progression of 17 months versus not reached (HR, 4.9; P 20% BM PCs had no prognostic value in a multivariate analysis that included serum free light-chain ratio >20, >2 g/dL M-protein, and >0.015% CTCs. The 20/2/20 and 20/2/0.015 models yielded similar risk stratification (C-index of 0.76 and 0.78). The combination of the 20/2/0.015 model with an immune risk score based on the percentages of SLAN+ and SLAN− nonclassical monocytes, CD69+HLADR+ cytotoxic NK cells, and CD4+CXCR3+ stem central memory T cells, allowed patient’ stratification into low, intermediate-low, intermediate-high, and high-risk disease with 0%, 20%, 39%, and 73% rates of progression at 2 years.Conclusions:This study showed that CTCs outperform BM PCs for assessing tumor burden. Additional analysis in larger series are needed to define a consensus cutoff of CTCs for minimally invasive stratification of SMM.

Discontinuations and dose reductions

Quality of life

Second primary malignancies

Exposure and remissions

Subgroup analysis by randomization strata II

AE incidence and severity

Purpose:For multiple myeloma, high-dose chemotherapy and autologous blood stem-cell transplantation (ASCT) followed by lenalidomide maintenance (LenMT) at 10–15 mg/day is considered standard of care. However, dose reductions due to side effects are common and median LenMT doses achieved over time may remain lower. Dose response during LenMT has never been investigated.Patients and Methods:In a multicenter, randomized, open-label trial, patients with multiple myeloma after ASCT and high-dose lenalidomide consolidation therapy (CT) at 25 mg/day were randomized to receive LenMT at either 25 or 5 mg/day. Primary endpoint was progression-free survival (PFS).Results:Ninety-four patients (median age, 58 years) were randomized to either arm, with 22% having International Staging System (ISS) stage 3 and 22% being in complete remission (CR). After median follow-up of 46.7 months, median doses of 14.5 and 5 mg/day were achieved in the two arms; 53% of dose reductions occurring during CT. In the high- and the low-dose arm, median PFS was 44.8 and 33.0 months (HR, 0.65; 95% CI, 0.44–0.97; P = 0.032), 36% and 23% of patients had stringent CR as best response (P = 0.08), and 4-year OS was 79% and 67% (P = 0.16), respectively. Hematologic toxicity, grade ≥3 neutropenia, and infections were initially more common with LenMT 25 mg, but decreased after dose adjustments. SPM incidence and quality-of-life (QoL) scores in both arms were similar.Conclusions:LenMT dose correlated with efficacy and toxicity. High rates of dose reductions during CT argue against a high starting dose. However, continuous up- and down-titration for each patient to the current maximum tolerated dose is prudent.

Centers and enrolment

Mass spectrometry (MS) is a promising tool for monitoring monoclonal protein in plasma cell dyscrasias. We included 480 transplant-eligible newly-diagnosed multiple myeloma (MM) patients from the GMMG-MM5 trial (EudraCT No. 2010-019173-16) and performed a retrospective MS analysis at baseline (480 patients) and at the pre-defined, consecutive time points after induction (444 patients), prior to maintenance (305 patients) and after one year of maintenance (227 patients). We found that MS negativity was significantly associated with improved progression-free survival (PFS) even in patients with complete response (CR) at all investigated follow-up time points. The prognostic impact was independent of established risk factors, such as the revised International Staging System. Combining MS and baseline cytogenetics improved the prediction of outcome: MS-positive patients with high-risk cytogenetics had a dismal PFS of 1.9 years (95% confidence interval [CI]: 1.6–2.3 years) from the start of maintenance. Testing the value of sequential MS prior to and after one year of maintenance, patients converting from MS positivity to negativity had an excellent PFS (median not reached) while patients converting from MS negativity to positivity progressed early (median 0.6 years, 95% CI: 0.3-not reached). Among patients with sustained MS positivity, the baseline high-risk cytogenetic status had a significant impact and defined a group with poor PFS. Combining minimal residual disease (MRD) in the bone marrow and MS allowed the identification of double negative patients with a favorable PFS (median 3.33 years, 95% CI: 3.08-not reached) and no overall survival events. Our study provides strong evidence that MS is superior to conventional response monitoring, highlighting the potential of MS to become a new standard. Our data indicate that MS should be performed sequentially and combined with baseline disease features and MRD to improve its clinical value.Clinical Trials Register: EudraCT No. 2010-019173-16

PURPOSE Patients with newly diagnosed multiple myeloma (NDMM) show heterogeneous outcomes, and approximately 60% of them are at intermediate-risk according to the Revised International Staging system (R-ISS), the standard-of-care risk stratification model. Moreover, chromosome 1q gain/amplification (1q+) recently proved to be a poor prognostic factor. In this study, we revised the R-ISS by analyzing the additive value of each single risk feature, including 1q+. PATIENTS AND METHODS The European Myeloma Network, within the HARMONY project, collected individual data from 10,843 patients with NDMM enrolled in 16 clinical trials. An additive scoring system on the basis of top features predicting progression-free survival (PFS) and overall survival (OS) was developed and validated. RESULTS In the training set (N = 7,072), at a median follow-up of 75 months, ISS, del(17p), lactate dehydrogenase, t(4;14), and 1q+ had the highest impact on PFS and OS. These variables were all simultaneously present in 2,226 patients. A value was assigned to each risk feature according to their OS impact (ISS-III 1.5, ISS-II 1, del(17p) 1, high lactate dehydrogenase 1, t(4;14) 1, and 1q+ 0.5 points). Patients were stratified into four risk groups according to the total additive score: low (Second Revision of the International Staging System [R2-ISS]-I, 19.2%, 0 points), low-intermediate (II, 30.8%, 0.5-1 points), intermediate-high (III, 41.2%, 1.5-2.5 points), high (IV, 8.8%, 3-5 points). Median OS was not reached versus 109.2 versus 68.5 versus 37.9 months, and median PFS was 68 versus 45.5 versus 30.2 versus 19.9 months, respectively. The score was validated in an independent validation set (N = 3,771, of whom 1,214 were with complete data to calculate R2-ISS) maintaining its prognostic value. CONCLUSION The R2-ISS is a simple prognostic staging system allowing a better stratification of patients with intermediate-risk NDMM. The additive nature of this score fosters its future implementation with new prognostic variables.

Intensive upfront therapy in newly-diagnosed multiple myeloma (MM) including induction therapy (IT), high-dose melphalan (MEL200), and autologous blood stem cell transplantation (ASCT) followed by consolidation and/or maintenance is mostly restricted to patients up to 65 years of age. Prospective phase III trial data in the era of novel agents for patients up to 70 years of age are not available. The GMMG-MM5 trial included 601 patients between 18 and 70 years of age, divided in three groups for the present analysis: ≤60 years (S1, n = 353), 61–65 years (S2, n = 107) and 66–70 years (S3, n = 141). Treatment consisted of a bortezomib-containing IT, MEL200/ASCT, consolidation, and maintenance with lenalidomide. Adherence to treatment was similar among patients of the three age groups. Overall toxicity during all treatment phases was increased in S2 and S3 compared to S1 (any adverse event/any serious adverse event: S1:81.7/41.8% vs. S2:90.7/56.5% vs. S3:87.2/68.1%, p = 0.05/p = 0.73), overall survival (log-rank p = 0.54) as well as time-to-progression (Gray’s p = 0.83) and non-relapse mortality (Gray’s p = 0.25), no differences were found between the three age groups. Our results imply that an intensive upfront therapy with a bortezomib-containing IT, MEL200/ASCT, lenalidomide consolidation, and maintenance should be applied to transplant-eligible MM patients up to 70 years of age.

The MM5 trial aimed at demonstrating a progression-free survival (PFS) difference in continued vs. response-adapted (in case of complete response, CR) lenalidomide (LEN) maintenance therapy (MT) in newly diagnosed, transplant-eligible multiple myeloma (MM). Patients were equally randomized to receive induction therapy with PAd (bortezomib/doxorubicin/dexamethasone) or VCD (bortezomib/cyclophosphamide/dexamethasone), high-dose melphalan and autologous blood stem cell transplantation, and LEN consolidation, followed by either LEN MT for a fixed duration of 2 years (LEN-2Y) or until achievement of CR (LEN-CR, intention-to-treat population n = 502): arms A1:PAd + LEN-2Y (n = 125), B1:PAd + LEN-CR (n = 126), A2:VCD + LEN-2Y (n = 126), B2:VCD + LEN-CR (n = 125). In the LEN-CR group (B1 + B2), n = 88/17.5% patients did not start or discontinued LEN MT due to CR. There was no PFS (p = 0.60, primary endpoint) nor overall survival (OS) (p = 0.15) difference between the four study arms. On pooled LEN MT strategies, OS (hazard ratio, hazard ratio [HR] = 1.42, p = 0.03) but not PFS (HR = 1.15, p = 0.20) was shorter in LEN-CR (B1 + B2) vs. LEN-2Y (A1 + A2) groups. PFS was shortened on landmark analyses from the start of LEN MT in patients being in CR in the LEN-CR group (LEN-CR vs. LEN-2Y, HR = 1.84, p = 0.02). OS from first progression was shortened in the LEN-CR vs. LEN-2Y group (HR = 1.60, p = 0.01). LEN MT should be applied beyond CR for at least 2 years.

The article Bortezomib-based induction, high-dose melphalan and lenalidomide maintenance in myeloma up to 70 years of age, written by Elias K. Mai, Kaya Miah, Uta Bertsch, Jan Dürig, Christof Scheid, Katja C. Weisel, Christina Kunz, Markus Munder, Hans- Walter Lindemann, Maximilian Merz, Dirk Hose, Anna Jauch, Anja Seckinger, Steffen Luntz, Sandra Sauer, Stephan Fuhrmann, Peter Brossart, Ahmet Elmaagacli, Martin Goerner, Helga Bernhard, Martin Hoffmann, Marc S. Raab, Igor W. Blau, Mathias Hänel, Axel Benner, Hans J. Salwender, and Hartmut Goldschmidt for the German-speaking Myeloma Multicenter Group (GMMG), was originally published Online First without Open Access. After publication in volume 35, pages 809–822, the author decided to opt for Open Choice and to make the article an Open Access publication. Therefore, the copyright of the article has been changed to © The Author(s) 2020 and the article is forthwith distributed under the terms of the Creative Commons Attribution. FUNDING Open Access funding enabled and organized by Projekt DEAL.

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Aim: To compare daratumumab plus standard-of-care (SoC; bortezomib/thalidomide/dexamethasone [VTd]) and VTd alone with other SoC for transplant-eligible newly diagnosed multiple myeloma. Patients & methods: We conducted an unanchored matching-adjusted indirect comparison of progression-free and overall survival (PFS/OS) with D-VTd/VTd versus bortezomib/lenalidomide/dexamethasone (VRd), bortezomib/cyclophosphamide/dexamethasone (VCd) and bortezomib/dexamethasone (Vd). Results: After matching adjustment, significant improvements in PFS were estimated for D-VTd versus VRd (hazard ratio [HR]: 0.47 [95% CI: 0.33–0.69]), VCd (HR: 0.35 [95% CI: 0.21–0.58]) and Vd (HR: 0.42 [95% CI: 0.28–0.63]). OS was significantly longer with D-VTd versus VRd (HR: 0.31 [95% CI: 0.16–0.57]), VCd (HR: 0.35 [95% CI: 0.14–0.86]) and Vd (HR: 0.38 [95% CI: 0.18–0.77]). No significant PFS/OS differences were seen for VTd versus other SoC. Conclusion: This analysis supports front-line daratumumab for transplant-eligible newly diagnosed multiple myeloma.

Lenalidomide (LEN) maintenance (MT) post autologous stem cell transplantation (ASCT) is standard of care in newly diagnosed multiple myeloma (MM) but has not been compared to other agents in clinical trials. We retrospectively compared bortezomib (BTZ; n = 138) or LEN (n = 183) MT from two subsequent GMMG phase III trials. All patients received three cycles of BTZ-based triplet induction and post-ASCT MT. BTZ MT (1.3 mg/m2 i.v.) was administered every 2 weeks for 2 years. LEN MT included two consolidation cycles (25 mg p.o., days 1–21 of 28 day cycles) followed by 10–15 mg/day for 2 years. The BTZ cohort more frequently received tandem ASCT (91% vs. 33%) due to different tandem ASCT strategies. In the LEN and BTZ cohort, 43% and 46% of patients completed 2 years of MT as intended (p = 0.57). Progression-free survival (PFS; HR = 0.83, p = 0.18) and overall survival (OS; HR = 0.70, p = 0.15) did not differ significantly with LEN vs. BTZ MT. Patients with n = 54 vs. BTZ: n = 84), LEN MT significantly improved PFS (HR = 0.61, p = 0.04) but not OS (HR = 0.46, p = 0.09). In conclusion, the significant PFS benefit after eliminating the impact of different tandem ASCT rates supports the current standard of LEN MT after ASCT.

Purpose: For multiple myeloma, high-dose chemotherapy and autologous blood stem-cell transplantation (ASCT) followed by lenalidomide maintenance (LenMT) at 10–15 mg/day is considered standard of care. However, dose reductions due to side effects are common and median LenMT doses achieved over time may remain lower. Dose response during LenMT has never been investigated. Patients and Methods: In a multicenter, randomized, open-label trial, patients with multiple myeloma after ASCT and high-dose lenalidomide consolidation therapy (CT) at 25 mg/day were randomized to receive LenMT at either 25 or 5 mg/day. Primary endpoint was progression-free survival (PFS). Results: Ninety-four patients (median age, 58 years) were randomized to either arm, with 22% having International Staging System (ISS) stage 3 and 22% being in complete remission (CR). After median follow-up of 46.7 months, median doses of 14.5 and 5 mg/day were achieved in the two arms; 53% of dose reductions occurring during CT. In the high- and the low-dose arm, median PFS was 44.8 and 33.0 months (HR, 0.65; 95% CI, 0.44–0.97; P = 0.032), 36% and 23% of patients had stringent CR as best response (P = 0.08), and 4-year OS was 79% and 67% (P = 0.16), respectively. Hematologic toxicity, grade ≥3 neutropenia, and infections were initially more common with LenMT 25 mg, but decreased after dose adjustments. SPM incidence and quality-of-life (QoL) scores in both arms were similar. Conclusions: LenMT dose correlated with efficacy and toxicity. High rates of dose reductions during CT argue against a high starting dose. However, continuous up- and down-titration for each patient to the current maximum tolerated dose is prudent.

The Dutch-Belgian Cooperative Trial Group for Hematology Oncology Group-65/German-speaking Myeloma Multicenter Group-HD4 (HOVON-65/GMMG-HD4) phase III trial compared bortezomib (BTZ) before and after high-dose melphalan and autologous stem cell transplantation (HDM, PAD arm) compared with classical cytotoxic agents prior and thalidomide after HDM (VAD arm) in multiple myeloma (MM) patients aged 18-65 years. Here, the long-term follow-up and data on second primary malignancies (SPM) are presented. After a median follow-up of 96 months, progression-free survival (censored at allogeneic transplantation, PFS) remained significantly prolonged in the PAD versus VAD arm (hazard ratio (HR) = 0.76, 95% confidence interval (95% CI) of 0.65-0.89, P = 0.001). Overall survival (OS) was similar in the PAD versus VAD arm (HR = 0.89, 95% CI: 0.74-1.08, P = 0.24). The incidence of SPM were similar between the two arms (7% each, P = 0.73). The negative prognostic effects of the cytogenetic aberration deletion 17p13 (clone size >= 10%) and renal impairment at baseline (serum creatinine > 2 mg dl(-1)) on PFS and OS remained abrogated in the PAD but not VAD arm. OS from first relapse/progression was similar between the study arms (HR = 1.02, P = 0.85). In conclusion, the survival benefit with BTZ induction/maintenance compared with classical cytotoxic agents and thalidomide maintenance is maintained without an increased risk of SPM.

Background: During the past decade, prognostic tools and outcomes of patients with newly-diagnosed multiple myeloma (NDMM) markedly improved. Data from clinical trials evaluating early morbidity and mortality including patients with transplant-eligible NDMM treated with novel agents are scarce. Thus, we aimed to analyze early morbidity and mortality in this patient cohort, devise and validate a predictive score to identify patients at risk. Patients and methods: Between July 2005 and January 2018, 1333 patients with transplant-eligible NDMM from three subsequent phase III trials, HD4, MM5 and HD6 from the German-speaking Myeloma Multicenter Group (GMMG), received a novel agent-based induction therapy with either bortezomib (BTZ) / doxorubicine / dexamethasone (DEX; PAD: n=192, HD4; PAd: n=296, MM5), BTZ / cyclophosphamide / DEX (VCD: n=300, MM5), BTZ / lenalidomide / DEX (VRD: n=272, HD6) or elotuzumab / VRD (ELO-VRD: n=273, HD6). Severe infections (SI) were defined as any infection grade ≥ 3 according to the Common Terminology Criteria for Adverse Events (CTCAE). SI and early deaths were counted on and up to 30 days post induction therapy. Uni-/multivariable logistic regression models were used to assess predictive factors for SI and early death and to account for trial effects. Data from the European Myeloma Network (EMN) 02 / Dutch-Belgian Cooperative Trial Group for Hematology Oncology Foundation (HOVON) 95 phase III trial including 1497 patients with transplant-eligible NDMM receiving induction therapy with VCD were used to validate a predictive score for SI and early mortality. Results: Overall, early mortality during induction therapy was low (n=24, 1.8%) in the GMMG cohort. SI were the most common cause for early deaths (n=15, 62.5%) as compared to MM progression-related death (n=5, 20.8%) and other causes (n=4, 16.7%). Rates of SI during induction therapy were 11.9% (n=159) and decreased in subsequent trial generations: HD4-PAD: 27.1%, MM5-PAd: 10.8%, MM5-VCD: 9.3%, HD6-VRD: 7.3% and HD6-ELO-VRD: 9.9% of patients. In the EMN02/HO95 trial, early mortality was 1.7% (n=25) and rates of SI were 6.8% (n=101). A multivariate model including patient and disease baseline characteristics identified four major risk factors for SI and/or early death on induction therapy in the GMMG cohort: age (>60 years; odds ratio [OR]=1.70, 95% confidence interval [95% CI]: 1.21-2.40, p=0.002), International Staging System (stage III; OR=1.92, 95% CI: 1.22-2.94, p=0.005), platelet count (1; OR=1.82, 95% CI: 1.10-3.06, p=0.022). A sum score based on these four risk factors (one risk factor = one point) was built and included 519 (39.5%), 550 (41.9%) and 245 (18.6%) patients with a score of 0, 1 and ≥2 points. A higher score gradually predicted an increasing risk for SI and/or death during induction therapy: 0 points=7.9%, 1 point=11.5% and ≥2 points=23.2% (p In the EMN02/HO95 cohort, 673 (45.6%), 587 (39.7%) and 217 (14.7%) patients had a score of 0, 1 and ≥2 points. The score was successfully validated in the EMN02/HO95 cohort: SI and/or death during induction therapy: 0 points=5.0%, 1 point=8.3% and ≥2 points=11.9% (p Conclusions: To date, this is the largest pooled analysis of individual patient data on early morbidity and mortality in patients with transplant-eligible NDMM treated with novel agent-based induction therapy. Our analysis highlights a decreasing incidence of SI and early mortality and proposes a validated, easy-to-use score to identify patients at excessive risk for SI and/or early death during induction therapy. This allows the implementation of intensive monitoring, preventive and supportive strategies for this subgroup of patients in further clinical trials and also routine care. Figure 1 Figure 1. Disclosures Mai: Celgene / BMS: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: travel accommodations and expenses, Research Funding; Glaxo Smith Kline: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: travel accommodations and expenses, Research Funding; Janssen-Cilag: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: travel accommodations and expenses, Research Funding; Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: travel accommodations and expenses, Research Funding. Salwender: AbbVie: Honoraria, Other: TRAVEL, ACCOMMODATIONS, EXPENSES; Amgen: Honoraria, Other: TRAVEL, ACCOMMODATIONS, EXPENSES; Takeda: Honoraria; Sanofi: Honoraria, Other: TRAVEL, ACCOMMODATIONS, EXPENSES; GlaxoSmithKline: Honoraria, Other: TRAVEL, ACCOMMODATIONS, EXPENSES; Janssen-Cilag: Honoraria, Other: TRAVEL, ACCOMMODATIONS, EXPENSES; Bristol-Myers Squibb/Celgene: Honoraria, Other: TRAVEL, ACCOMMODATIONS, EXPENSES; Oncopeptides: Honoraria; Chugai: Honoraria; Pfizer: Honoraria. Zweegman: Oncopeptides: Membership on an entity's Board of Directors or advisory committees; Sanofi: Membership on an entity's Board of Directors or advisory committees; BMS: Membership on an entity's Board of Directors or advisory committees; Takeda: Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen: Membership on an entity's Board of Directors or advisory committees, Research Funding. Munder: GSK: Consultancy; BMS: Consultancy, Honoraria; Abbvie: Consultancy; Takeda: Consultancy, Honoraria; Amgen: Honoraria; Sanofi: Consultancy; Janssen: Consultancy, Honoraria; Incyte: Research Funding. Pantani: Janssen: Honoraria; Amgen: Honoraria. Brossart: BMS: Consultancy, Honoraria, Research Funding; Amgen: Consultancy, Honoraria; MSD: Honoraria. Beksac: Amgen: Consultancy, Speakers Bureau; Janssen: Consultancy, Speakers Bureau; Celgene: Consultancy, Speakers Bureau; Sanofi: Consultancy, Speakers Bureau; Takeda: Consultancy, Speakers Bureau; Oncopeptides: Consultancy. Raab: BMS: Consultancy, Membership on an entity's Board of Directors or advisory committees; Roche: Consultancy; Abbvie: Consultancy, Honoraria; Novartis: Membership on an entity's Board of Directors or advisory committees, Research Funding; GSK: Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees; Sanofi: 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; Janssen: Membership on an entity's Board of Directors or advisory committees. Dürig: Celgene: Membership on an entity's Board of Directors or advisory committees, Other: Travel Support, Speakers Bureau; Janssen: Membership on an entity's Board of Directors or advisory committees, Other: Travel Support, Speakers Bureau; Takeda: Membership on an entity's Board of Directors or advisory committees; BMS: Membership on an entity's Board of Directors or advisory committees. Besemer: Takeda: Honoraria; Janssen: Honoraria; GSK: Honoraria. Fenk: GSK: Honoraria; Amgen: Honoraria; Janssen: Honoraria; BMS/Celgene: Honoraria; Takeda: Honoraria. Haenel: Bayer Vital: Honoraria; Jazz: Consultancy, Honoraria; GSK: Consultancy; Takeda: Consultancy, Honoraria; Roche: Consultancy, Honoraria; Novartis: Consultancy, Honoraria; Amgen: Consultancy; Celgene: Consultancy, Honoraria. Metzler: Takeda: Consultancy; BMS: Consultancy; GSK: Consultancy; Amgen: Consultancy; Janssen: Consultancy; AstraZeneca: Consultancy; Pfizer: Consultancy; Sanofi: Consultancy. Graeven: Amgen: Honoraria; Sanofi Aventis: Honoraria; Celgene: Honoraria, Research Funding; Johnson and Johnson: Honoraria; Astra Zeneca: Honoraria; MSD: Consultancy; Boehringer Ingelheim: Honoraria; BMS: Honoraria; Fujifilm: Honoraria; Roche: Research Funding; Gilead: Research Funding; Ipsen Bioscience: Research Funding; MacroGenics: Research Funding. Boccadoro: Janssen and GSK: Membership on an entity's Board of Directors or advisory committees; Sanofi, Celgene, Amgen, Janssen, Novartis, Bristol-Myers Squibb, and AbbVie: Honoraria; Sanofi, Celgene, Amgen, Janssen, Novartis, Bristol-Myers Squibb, and Mundipharma: Research Funding. Scheid: Novartis: 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, Research Funding; Roche: Consultancy; Abbvie: Honoraria; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen: 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. Dimopoulos: Janssen: Honoraria; BMS: Honoraria; Amgen: Honoraria; Takeda: Honoraria; Beigene: Honoraria. Weisel: Oncopeptides: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Bristol Myers Squibb: 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; Roche: Honoraria; 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; GSK: 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, Research Funding; Karyopharm: 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; Sanofi: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Abbvie: Consultancy; Novartis: Honoraria; Pfizer: Honoraria. Cavo: Adaptive Biotechnologies: Consultancy, Honoraria; Novartis: Honoraria; GlaxoSmithKline: Consultancy, Honoraria; Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel Accommodations, Speakers Bureau; Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; 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, Speakers Bureau; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: TRAVEL, ACCOMMODATIONS, EXPENSES, Speakers Bureau; Sanofi: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Bristol-Myers Squib: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Sonneveld: SkylineDx: Honoraria, Research Funding; Karyopharm: Consultancy, Honoraria, Research Funding; Celgene/BMS: Consultancy, Honoraria, Research Funding; Janssen: Consultancy, Honoraria, Research Funding; Amgen: Consultancy, Honoraria, Research Funding; Takeda: Consultancy, Honoraria, Research Funding. Goldschmidt: Mundipharma: Research Funding; Incyte: Research Funding; Janssen: Consultancy, Honoraria, Other: Grants and/or Provision of Investigational Medicinal Product, Research Funding; Johns Hopkins University: Other: Grant; Molecular Partners: Research Funding; MSD: Research Funding; GSK: Honoraria; Chugai: Honoraria, Other: Grants and/or Provision of Investigational Medicinal Product, Research Funding; Celgene: Consultancy, Honoraria, Other: Grants and/or Provision of Investigational Medicinal Product, Research Funding; BMS: Consultancy, Honoraria, Other: Grants and/or Provision of Investigational Medicinal Product, Research Funding; Adaptive Biotechnology: Consultancy; Amgen: Consultancy, Honoraria, Other: Grants and/or Provision of Investigational Medicinal Product, Research Funding; Novartis: Honoraria, Research Funding; Dietmar-Hopp-Foundation: Other: Grant; Sanofi: Consultancy, Honoraria, Other: Grants and/or Provision of Investigational Medicinal Product, Research Funding; Takeda: Consultancy, Research Funding.

Background: In newly-diagnosed multiple myeloma (NDMM), lenalidomide/bortezomib/dexamethasone (RVd) is one of the most widely used combination regimens. Anti-CD38 monoclonal antibodies (CD38-moAb) increase efficacy when added to standard-of-care regimens. Here we present the first primary endpoint of the randomized, open-label, multicenter, phase III GMMG-HD7 trial, comparing RVd without (arm IA) or with the CD38-moAb isatuximab (Isa, arm IB) with regard to the rate of minimal residual disease (MRD) negativity after induction therapy in patients with transplant-eligible NDMM. Patients and Methods: Patients with transplant-eligible NDMM at 67 sites in Germany were equally randomized to receive three 42-day cycles of RVd (lenalidomide 25 mg/d p.o., d1-14 and d22-35; bortezomib 1.3 mg/m 2 s.c. d1, 4, 8, 11, 22, 25, 29, 32; dexamethasone 20 mg/d d1-2, 4-5, 8-9, 11-12, 15, 22-23, 25-26, 29-30, 32-33) in both arms. Isa was added to arm IB only (10 mg/kg i.v., cycle 1: d 1, 8, 15, 22, 29; cycles 2-3: d 1, 15, 29). Randomization for induction was stratified according to revised International Staging System (R-ISS). Primary endpoint of the trial was MRD negativity assessed by next-generation flow (NGF, cut off 1x10 -5) after induction. Secondary endpoints included rates of complete response (CR) after induction and safety. Data cut-off for the present analysis was April 2021. Results: Between 10/2018 and 09/2020, 662 patients were included in the trial. 660 patients were eligible for intention-to-treat analysis and 658 patients started induction (RVd: 329/328 and Isa-RVd: 331/330). Median age was 58 (range 26-70) years and baseline characteristics were well balanced between treatment arms. On induction, 35 (10.6%) and 18 (5.4%) patients discontinued treatment in the RVd vs. Isa-RVd arms (p=0.02). Among these, 8 (2.4%, RVd) vs. 7 (2.1%, Isa-RVd) patients discontinued induction due to adverse events (AE). 293 (89.1%) vs. 312 (94.3%) patients in the RVd vs. Isa-RVd arms continued further study treatment after induction. MRD negativity rates after induction were 35.6% vs. 50.1% (odds ratio [OR]=1.83, 95% confidence interval [95% CI]: 1.34-2.51, p At least one AE (grade ≥3) on induction occurred in 61.3% (RVd) and 63.6% (Isa-RVd) of patients (p=0.57). Most common AE (grade ≥3) by system organ class (SOC) for RVd vs. Isa-RVd were: "investigations": 23.5% vs. 23.9% (p=0.93), "blood and lymphatic system disorders": 16.8% vs. 25.8% (p=0.006), "infections and infestations": 10.4% vs. 13.0% (p=0.33) and "nervous system disorders": 10.1% vs. 8.5% (p=0.50). Rates of serious AE (SAE, any grade) on induction were similar between RVd and Isa-RVd (36.3% vs. 34.8%, p=0.75). Eight (RVd) and four (Isa-RVd) patients died during induction. Conclusions: The GMMG-HD7 trial met its primary endpoint. To the best of our knowledge this is the first phase III trial to demonstrate superiority of MRD negativity rates after induction by adding a CD38-moAb to RVd. There were no increased rates of SAE or early discontinuation in patients treated with Isa-RVd compared to RVd. The trial is ongoing, including analyses post autologous transplantation, which is followed by a second randomization to compare the efficacy of the addition of Isa to lenalidomide maintenance. Disclosures Goldschmidt: Takeda: Consultancy, Research Funding; Sanofi: Consultancy, Honoraria, Other: Grants and/or Provision of Investigational Medicinal Product, Research Funding; Adaptive Biotechnology: Consultancy; Incyte: Research Funding; GSK: Honoraria; Chugai: Honoraria, Other: Grants and/or Provision of Investigational Medicinal Product, Research Funding; Celgene: Consultancy, Honoraria, Other: Grants and/or Provision of Investigational Medicinal Product, Research Funding; BMS: Consultancy, Honoraria, Other: Grants and/or Provision of Investigational Medicinal Product, Research Funding; Janssen: Consultancy, Honoraria, Other: Grants and/or Provision of Investigational Medicinal Product, Research Funding; Johns Hopkins University: Other: Grant; Molecular Partners: Research Funding; MSD: Research Funding; Mundipharma: Research Funding; Dietmar-Hopp-Foundation: Other: Grant; Novartis: Honoraria, Research Funding; Amgen: Consultancy, Honoraria, Other: Grants and/or Provision of Investigational Medicinal Product, Research Funding. Mai: Celgene / BMS: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: travel accommodations and expenses, Research Funding; Glaxo Smith Kline: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: travel accommodations and expenses, Research Funding; Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: travel accommodations and expenses, Research Funding; Janssen-Cilag: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: travel accommodations and expenses, Research Funding. Fenk: Takeda: Honoraria; GSK: Honoraria; Amgen: Honoraria; Janssen: Honoraria; BMS/Celgene: Honoraria. Besemer: Takeda: Honoraria; Janssen: Honoraria; GSK: Honoraria. Dürig: Janssen: Membership on an entity's Board of Directors or advisory committees, Other: Travel Support, Speakers Bureau; Celgene: Membership on an entity's Board of Directors or advisory committees, Other: Travel Support, Speakers Bureau; Takeda: Membership on an entity's Board of Directors or advisory committees; BMS: Membership on an entity's Board of Directors or advisory committees. Schroers: BMS/Celgene: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; GSK: Consultancy, Honoraria; Takeda: Honoraria. Metzler: Takeda: Consultancy; BMS: Consultancy; GSK: Consultancy; Amgen: Consultancy; Janssen: Consultancy; AstraZeneca: Consultancy; Pfizer: Consultancy; Sanofi: Consultancy. Haenel: Takeda: Consultancy, Honoraria; Jazz: Consultancy, Honoraria; GSK: Consultancy; Bayer Vital: Honoraria; Roche: Consultancy, Honoraria; Novartis: Consultancy, Honoraria; Amgen: Consultancy; Celgene: Consultancy, Honoraria. Mann: Cellgene: Consultancy. Asemissen: GSK: Honoraria; Pfizer: Honoraria; Celgene BMS: Honoraria. Heilmeier: Sanofi-Aventis Dtld. GmbH: Consultancy. Kriegsmann: Sanofi: Honoraria. Weinhold: Sanofi: Honoraria. Holderried: Amgen: Speakers Bureau; GSK: Consultancy, Membership on an entity's Board of Directors or advisory committees; Eurocept Pharmaceuticals: Other: Travel support; MSD: Speakers Bureau; Gilead Sciences: Consultancy, Membership on an entity's Board of Directors or advisory committees; Abbvie: Other: Travel support; Sanofi: Consultancy, Membership on an entity's Board of Directors or advisory committees; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees; Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees; Janssen: Other: Travel support; Therakos: Other: Travel support; Daiichi Sankyo: Other: travel support; Medac: Other: Travel support; Jazz Pharmaceuticals: Consultancy, Membership on an entity's Board of Directors or advisory committees. Trautmann-Grill: Sanofi: Consultancy, Honoraria; Takeda: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; GSK: Consultancy, Honoraria. Gezer: Amgen: Consultancy, Other: Invited Speaker; Takeda: Consultancy, Other: Invited Speaker; BMS: Consultancy, Other: Invited Speaker; Celgene: Consultancy, Other: Invited Speaker. Khandanpour: GSK: Honoraria; Takeda: Honoraria; Janssen: Honoraria; AstraZeneca: Honoraria, Research Funding; Pfizer: Honoraria; Sanofi: Honoraria, Research Funding; BMS/Celgene: Honoraria. Knauf: Amgen: Honoraria; Abbvie: Honoraria; Beigene: Consultancy, Honoraria; BMS: Honoraria; Celgene: Honoraria; Janssen: Consultancy, Honoraria; Sanofi: Honoraria; AstraZeneca: Consultancy, Honoraria. Munder: GSK: Consultancy; Amgen: Honoraria; Sanofi: Consultancy; Takeda: Consultancy, Honoraria; Abbvie: Consultancy; BMS: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; Incyte: Research Funding. Hoffmann: Sanofi-Aventis: Consultancy. Raab: Roche: Consultancy; GSK: Honoraria, 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; Celgene: Membership on an entity's Board of Directors or advisory committees; Sanofi: Membership on an entity's Board of Directors or advisory committees, Research Funding; Abbvie: Consultancy, Honoraria; Janssen: Membership on an entity's Board of Directors or advisory committees; BMS: 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. Salwender: GlaxoSmithKline: Honoraria, Other: TRAVEL, ACCOMMODATIONS, EXPENSES; Sanofi: Honoraria, Other: TRAVEL, ACCOMMODATIONS, EXPENSES; Chugai: Honoraria; Oncopeptides: Honoraria; Takeda: Honoraria; Amgen: Honoraria, Other: TRAVEL, ACCOMMODATIONS, EXPENSES; AbbVie: Honoraria, Other: TRAVEL, ACCOMMODATIONS, EXPENSES; Janssen-Cilag: Honoraria, Other: TRAVEL, ACCOMMODATIONS, EXPENSES; Bristol-Myers Squibb/Celgene: Honoraria, Other: TRAVEL, ACCOMMODATIONS, EXPENSES; Pfizer: Honoraria. Weisel: Adaptive Biotechnologies: 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; Bristol Myers Squibb: 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; Amgen: 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; Karyopharm: 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; 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; Abbvie: Consultancy; Novartis: Honoraria; Pfizer: Honoraria. OffLabel Disclosure: Isatuximab prior to ASCT in NDMM

Background: Treatment regimens including a proteasome inhibitor, immunomodulating agent and a monoclonal antibody (moAb) play an emerging role in the treatment of newly-diagnosed multiple myeloma (NDMM). This multicenter phase III trial of the German-speaking Myeloma Multicenter Group (GMMG HD6) investigated the addition of the anti-SLAMF7 moAb elotuzumab to lenalidomide / bortezomib / dexamethasone (RVd) in induction and consolidation therapy as well as to lenalidomide maintenance treatment in transplant-eligible NDMM. Patients and Methods: Patients were equally randomized into four treatment arms, stratified by International Staging System (ISS). Treatment consisted of four 21-day cycles of RVd (arms A1/A2) or elotuzumab-RVd (arms B1/B2) induction therapy, respectively. High-dose melphalan (HDM) and autologous blood stem cell transplantation (ASCT) were followed by two 21-day cycles of RVd or elotuzumab-RVd consolidation and lenalidomide or elotuzumab-lenalidomide maintenance for two years (arms A1/B1 vs. A2/B2). Primary objective of the trial was determination of the best of four treatment strategies regarding progression-free survival (PFS) from randomization. Secondary endpoints included overall survival (OS), response rates and safety. Results: Between 06/2015 and 09/2017, 564 patients were included in the trial. The evaluable intention-to-treat (ITT) and safety population comprised 559 and 555 patients (A1: n=139/137; A2: n=141/138; B1: n=137/138; B2: n=142/142). Median age at randomization was 59 (range 27-70) years. Baseline characteristics were well balanced between the four treatment arms. Four cycles of induction therapy were completed by 517 patients (92.5% of ITT). At least one HDM/ASCT was applied in 495 (88.6%), of which 116 patients (20.8%) received tandem HDM/ASCT. Consolidation and maintenance therapy were initiated in 469 (83.9%) and 454 (81.2%) patients, respectively. Rates of very good partial response or better (≥VGPR) prior to start of consolidation therapy were 78.9%, 78.2%, 81.5% and 80.7% in arms A1, A2, B1 and B2, respectively (p=0.95). With a median follow-up time of 49.8 months, PFS was not significantly different between the four treatment arms (adjusted log-rank p value stratified by ISS, p=0.86; primary endpoint). OS was similar in all treatment arms (stratified log-rank p=0.43). 3-year PFS/OS rates are 68.8%/89.4%, 68.5%/89.1%, 66.2%/92.5% and 67.2%/89.7% in arm A1, A2, B1 and B2, respectively. Multivariate analyses including age, sex, ISS stage, performance status, serum lactate dehydrogenase level, renal impairment at diagnosis, adverse cytogenetics (del17p, t[4;14] and t[14;16]) and treatment arms identified ISS stages II and III (hazard ratio [HR]=1.42/2.04, 95% confidence interval [95% CI]= 1.00-2.02/1.36-3.07, p=0.048/ On induction, consolidation and maintenance treatment, at least one (serious) adverse event (grade ≥3 for all AE or ≥2 for infections and infestations, neuropathy, cardiac disorders and thromboembolic events, and any grade for serious AE) occurred in 95.6%, 91.3%, 92.8% and 89.4% of patients in arm A1, A2, B1 and B2, respectively (p=0.25). Most common system organ classes (SOCs) were "infections and infestations", "neurological disorders", "blood and lymphatic system disorders", and "investigations" with no significant differences between the four treatment arms (p=0.39/0.64/0.13/0.42). Overall AE/SAE during lenalidomide vs. elotuzumab-lenalidomide maintenance were comparable (A1/B1: 65.5% vs. A2/B2: 66.4%,p=0.86), though SOC "infections and infestations" was increased in the elotuzumab-lenalidomide arms (A1/B1: 42.9% vs. A2/B2: 51.4%, p=0.05). Conclusions: This is the first phase III trial evaluating elotuzumab in patients with transplant-eligible NDMM. The addition of elotuzumab to RVd induction/consolidation therapy and lenalidomide maintenance did not result in improved PFS or OS. This is in line with previous reports from the ELOQUENT-1 and SWOG-1211 trials, investigating elotuzumab in non-transplant-eligible and high-risk NDMM, while elotuzumab-based combination therapies are effective in relapsed MM (ELOQUENT-2/-3 trials). Further analyses to identify potential subgroups that benefit from elotuzumab-based treatment in our trial are ongoing. Disclosures Goldschmidt: Incyte: Research Funding; BMS: Consultancy, Honoraria, Other: Grants and/or Provision of Investigational Medicinal Product, Research Funding; Celgene: Consultancy, Honoraria, Other: Grants and/or Provision of Investigational Medicinal Product, Research Funding; Chugai: Honoraria, Other: Grants and/or Provision of Investigational Medicinal Product, Research Funding; GSK: Honoraria; Janssen: Consultancy, Honoraria, Other: Grants and/or Provision of Investigational Medicinal Product, Research Funding; Johns Hopkins University: Other: Grant; Molecular Partners: Research Funding; MSD: Research Funding; Mundipharma: Research Funding; Novartis: Honoraria, Research Funding; Dietmar-Hopp-Foundation: Other: Grant; Sanofi: Consultancy, Honoraria, Other: Grants and/or Provision of Investigational Medicinal Product, Research Funding; Takeda: Consultancy, Research Funding; Adaptive Biotechnology: Consultancy; Amgen: Consultancy, Honoraria, Other: Grants and/or Provision of Investigational Medicinal Product, Research Funding. Mai: Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: travel accommodations and expenses, Research Funding; Glaxo Smith Kline: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: travel accommodations and expenses, Research Funding; Celgene / BMS: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: travel accommodations and expenses, Research Funding; Janssen-Cilag: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: travel accommodations and expenses, Research Funding. Besemer: GSK: Honoraria; Janssen: Honoraria; Takeda: Honoraria. Haenel: Jazz: Consultancy, Honoraria; GSK: Consultancy; Bayer Vital: Honoraria; Takeda: Consultancy, Honoraria; Roche: Consultancy, Honoraria; Novartis: Consultancy, Honoraria; Amgen: Consultancy; Celgene: Consultancy, Honoraria. Fenk: Janssen: Honoraria; Amgen: Honoraria; GSK: Honoraria; Takeda: Honoraria; BMS/Celgene: Honoraria. Munder: Janssen: Consultancy, Honoraria; BMS: Consultancy, Honoraria; Abbvie: Consultancy; Takeda: Consultancy, Honoraria; Amgen: Honoraria; Sanofi: Consultancy; GSK: Consultancy; Incyte: Research Funding. Dürig: Celgene: Membership on an entity's Board of Directors or advisory committees, Other: Travel Support, Speakers Bureau; Janssen: Membership on an entity's Board of Directors or advisory committees, Other: Travel Support, Speakers Bureau; Takeda: Membership on an entity's Board of Directors or advisory committees; BMS: Membership on an entity's Board of Directors or advisory committees. Hose: LamKap Bio: Consultancy, Current Employment; BMS: Research Funding. Scheid: Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees; Roche: Consultancy; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Abbvie: Honoraria; 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, Research Funding; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees. Schroers: BMS/Celgene: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; GSK: Consultancy, Honoraria; Takeda: Honoraria. Metzler: GSK: Consultancy; Amgen: Consultancy; Janssen: Consultancy; AstraZeneca: Consultancy; Pfizer: Consultancy; Sanofi: Consultancy; BMS: Consultancy; Takeda: Consultancy. Schieferdecker: Sebia: Consultancy. Mahlberg: Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Abbvie: Honoraria; BMS: Honoraria; GSK: Honoraria. Graeven: Amgen: Honoraria; Sanofi Aventis: Honoraria; Celgene: Honoraria, Research Funding; Johnson & Johnson: Honoraria; Astra Zeneca: Honoraria; MSD: Consultancy; Boehringer Ingelheim: Honoraria; BMS: Honoraria; Fujifilm: Honoraria; Roche: Research Funding; Gilead: Research Funding; Ipsen Bioscience: Research Funding; MacroGenics: Research Funding. Martens: Celgene: Consultancy; Sanofi-Aventis: Consultancy. Weisel: Adaptive Biotechnologies: 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; Amgen: 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; GSK: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Bristol Myers Squibb: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Karyopharm: 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; Roche: Honoraria; Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Abbvie: Consultancy; Novartis: Honoraria; Pfizer: Honoraria. Raab: Roche: Consultancy; Celgene: Membership on an entity's Board of Directors or advisory committees; Amgen: Consultancy, Membership on an entity's Board of Directors or advisory committees; Sanofi: 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; GSK: Honoraria, Membership on an entity's Board of Directors or advisory committees; Abbvie: Consultancy, Honoraria; Janssen: Membership on an entity's Board of Directors or advisory committees; BMS: Consultancy, Membership on an entity's Board of Directors or advisory committees. Salwender: Takeda: Honoraria; Sanofi: Honoraria, Other: TRAVEL, ACCOMMODATIONS, EXPENSES; GlaxoSmithKline: Honoraria, Other: TRAVEL, ACCOMMODATIONS, EXPENSES; Oncopeptides: Honoraria; Chugai: Honoraria; Amgen: Honoraria, Other: TRAVEL, ACCOMMODATIONS, EXPENSES; AbbVie: Honoraria, Other: TRAVEL, ACCOMMODATIONS, EXPENSES; Janssen-Cilag: Honoraria, Other: TRAVEL, ACCOMMODATIONS, EXPENSES; Bristol-Myers Squibb/Celgene: Honoraria, Other: TRAVEL, ACCOMMODATIONS, EXPENSES; Pfizer: Honoraria. OffLabel Disclosure: Lenalidomide and ELotuzumab in first line therapy prior to autologous stem cell transplantation, Elotuzumab in maintenance after autologous transplantation.