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Multiple myeloma gammopathies

Salvage autologous transplant and lenalidomide maintenance vs. lenalidomide/dexamethasone for relapsed multiple myeloma: the randomized GMMG phase III trial ReLApsE


The role of salvage high-dose chemotherapy and autologous stem cell transplantation (sHDCT/ASCT) for relapsed and/or refractory multiple myeloma (RRMM) in the era of continuous novel agent treatment has not been defined. This randomized, open-label, phase III, multicenter trial randomized patients with 1st–3rd relapse of multiple myeloma (MM) to a transplant arm (n = 139) consisting of 3 Rd (lenalidomide 25 mg, day 1–21; dexamethasone 40 mg, day 1, 8, 15, and 22; 4-week cycles) reinduction cycles, sHDCT (melphalan 200 mg/m2), ASCT, and lenalidomide maintenance (10 mg/day) or to a control arm (n = 138) of continuous Rd. Median PFS was 20.7 months in the transplant and 18.8 months in the control arm (HR 0.87; 95% CI 0.65–1.16; p = 0.34). Median OS was not reached in the transplant and 62.7 months in the control arm (HR 0.81; 95% CI 0.52–1.28; p = 0.37). Forty-one patients (29%) did not receive the assigned sHDCT/ASCT mainly due to early disease progression, adverse events, and withdrawal of consent. Multivariate landmark analyses from the time of sHDCT showed superior PFS and OS (p = 0.0087/0.0057) in patients who received sHDCT/ASCT. Incorporation of sHDCT/ASCT into relapse treatment with Rd was feasible in 71% of patients and did not significantly prolong PFS and OS on ITT analysis while patients who received sHDCT/ASCT may have benefitted.

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Fig. 1: CONSORT diagram.
Fig. 2: Progression-free survival (PFS) and overall survival (OS) in the intention-to-treat population.
Fig. 3: Progression-free (PFS) and overall survival (OS) landmark analysis from high-dose chemotherapy (HDCT; transplant arm) and Rd cycle 5 (control arm).

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The trial was designed and conducted by the German Myeloma Multicenter Group (GMMG). We thank all investigators, study nurses, research staff, the coordination centers for clinical trials (KKS) in Heidelberg and Leipzig, and—most importantly—the participating patients and their families. Furthermore we thank the Dietmar Hopp-Stiftung, Celgene, Chugai, and Amgen for their support of the trial.

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Authors and Affiliations




HG designed the trial and HG, MAB, JS, NB, CH and TH analyzed the data. HG, MAB, JS, MSR, JH, AJ, PB, MG, SK, MS-H, PR, UG, RF, MH, HM, HWL, CS, AN, HS, RN, and KW collected data. MAB wrote and all co-authors revised and approved the article.

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Correspondence to Hartmut Goldschmidt.

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Conflict of interest

HG—Amgen: consultancy, research funding; Novartis: honoraria, research funding; ArtTempi: honoraria; Janssen: consultancy, honoraria, research funding; Sanofi: consultancy, research funding; Mundipharma: research funding; Takeda: consultancy, research funding; Celgene: consultancy, honoraria, research funding; Bristol-Myers Squibb: consultancy, honoraria, research funding; Adaptive Biotechnology: consultancy; Chugai: honoraria, research funding. MAB—Takeda: consultancy, honoraria; Novartis: consultancy, research funding. Travel support: Celgene, Amgen, and Janssen. M-SB: Celgene: consultancy, honoraria; Novartis: consultancy, honoraria, research funding; BMS: consultancy, honoraria, research funding; Amgen: consultancy, honoraria, research funding. JH—Janssen: honoraria, advisory board; Amgen: advisory board; BMS: honoraria, advisory board, research funding; Oncotracker: advisory board; Adaptive Biotech: advisory board; GSK: advisory board. Celgene: consultancy, honoraria, Other: advisory board, research funding. CM-T—research funding: Pfizer, Daiichi Sankyo, BiolineRx, Bayer; advisory boards: Pfizer, Janssen. MS-H—consultancy: Celgene; financial support of educational meetings: Janssen, Takeda, Novartis, Pfizer, Roche, Vifor, Celgene. PR—Honoraria: Takeda, BMS, Roche, Celgene, Sanofi-Aventis; travel support: Celgene, Takeda, Abbvie. UG—honoraria: Sirtex, Daiichi Sankyo, Boehringer Ingelheim, Amgen, Servier, AstraZeneca; consultancy, advisory boards: Merck, BMS, Hexal, Amgen, Celgene, Johnson & Johnson, MSD; travel support: Merck, Amgen, Boehringer Ingelheim. RF—Takeda: honoraria; Bristol-Meyers Squibb: honoraria, Other: travel grant; Celgene: honoraria, Other: travel grant, research funding; Janssen: honoraria; Amgen: honoraria. MH—Novartis: honoraria; Roche: honoraria; Amgen: honoraria; Takeda: honoraria. CS—Novartis: honoraria, research funding; Takeda: honoraria, research funding; Janssen: honoraria, research funding; Celgene: honoraria; BMS: honoraria; Amgen: honoraria; GSK: honoraria. AN—honoraria: Celgene, Takeda, Amgen, Alexion, Sanofi, Janssen, BMS. Research funding: Celgene, Janssen, Takeda. Travel support: Celgene, Takeda, Alexion. HS—Celgene: honoraria, Other: travel suppport, research funding; Janssen: honoraria, Other: travel support, research funding; Novartis: honoraria, Other: travel suppport, research funding; Takeda: honoraria; Amgen: honoraria, Other: travel suppport, research funding; Bristol-Myers Squibb: honoraria, Other: travel suppport, research funding. BB—Janssen: honoraria. KW—Amgen, Celgene, Janssen, and Sanofi: research funding; Amgen, BMS, Celgene, Janssen, Takeda, Adaptive Biotech: honoraria; Amgen, Adaptive Biotech, BMS, Celgene, Janssen, Juno, Sanofi, GSK, Karyopharm and Takeda: consultancy, membership on an entity’s Board of Directors or advisory committees.

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Goldschmidt, H., Baertsch, MA., Schlenzka, J. et al. Salvage autologous transplant and lenalidomide maintenance vs. lenalidomide/dexamethasone for relapsed multiple myeloma: the randomized GMMG phase III trial ReLApsE. Leukemia 35, 1134–1144 (2021).

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