Sidana S, Kumar S, Fraser R, Estrada-Merly N, Giralt S, Agrawal V, Anderson LD Jr, Aljurf M, Banerjee R, Bashey A, Battiwalla M, Beitinjaneh A, Chakraborty R, Chhabra S, Dhakal B, Dholaria B, Hashmi S, Janakiram M, Lee C, Lekakis L, Murthy HS, Parrondo R, Wangjam T, Usmani S, Shah N, Qazilbash M, and D'Souza A
Bortezomib-based triplet regimens-specifically bortezomib, lenalidomide, and dexamethasone (VRD) and bortezomib, cyclophosphamide, and dexamethasone (VCD)-are the 2 most common induction regimens used in transplantation-eligible patients with newly diagnosed multiple myeloma (NDMM), with conflicting data on comparative efficacy and outcomes in this population. We compared long-term outcomes of patients with NDMM receiving VRD induction and those receiving VCD induction prior to autologous stem cell transplantation (ASCT). Patients registered with the Center for International Blood and Marrow Transplant Registry were included if they had undergone ASCT for MM within 6 months of diagnosis between January 2013 and December 2018, received VRD or VCD induction, and achieved a pretransplantation partial or better response. Of 1135 patients, 914 received VRD and 221 received VCD. The patients receiving VCD were more likely to have renal impairment and International Staging System (ISS) stage III disease and less likely to receive full-dose melphalan (200 mg/m 2 ) conditioning (69% versus 80%; P < .001). Very good partial response rates pretransplantation, post-transplantation, and at best response were not significantly different in the 2 groups. Maintenance use was more common after VRD induction (88% versus 76%; P < .001), with lenalidomide the most common agent (80% versus 63%). Patients in the VRD group had a higher rate of renal recovery (74% versus 43%; P < .001), possibly due to a rapid reduction of light chains in the VRD group or improvement in renal function with VCD, which allowed a switch over to VRD, as patients who switched were classified in the VRD group. Patients receiving VRD had better survival on univariate analysis, with a median progression-free survival (PFS) from transplantation of 44.6 months versus 34.1 months (P = .004) and median 5-year overall survival (OS) of 79% versus 60% (P < .001). Multivariate analysis showed no significant survival difference, with a hazard ratio for VCD versus VRD induction of 1.22 (95% CI, 0.96 to 1.55; P = .10) for PFS and 1.33 (95% CI, 0.93 to 1.92, P = .12) for OS. Maintenance use was independently associated with superior PFS and OS, along with ISS stage, cytogenetics, and pretransplantation response (PFS only). In patients with MM undergoing upfront ASCT after VRD or VCD induction, no independent survival difference was seen based on the induction therapy received after adjusting for other prognostic factors. The use of maintenance treatment was uniformly associated with superior outcomes. © 2021 American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc., Competing Interests: Conflict of interest statement S.S. has served as a consultant for Janssen and has received research funding from Janssen, Magenta Therapeutics, and Allogene. A.D. has served as a consultant for Janssen; has received research funding from Takeda, Sanofi, and TeneoBio; and has served on advisory boards for Imbrium, Pfizer, and Akcea. S.K. reports receipt of grants and other remuneration from BMS/Celgene, Takeda, AbbVie, Roche and Janssen; grants from Medimmune, Tenebio, and Carsgen; and personal fees from Oncopeptides. S.U. reports receipt of grants and personal fees from Amgen, Celgene, Sanofi, Seattle Genetics, Janssen, Takeda, SkylineDX, and Merck; grants from BMS and Pharmacyclics; and personal fees from AbbVie and MundiPharma. N.S. reports receipt of grants from Celgene/BMS, Janssen, bluebird bio, Sutro Biopharma, Teneobio, Poseida, and Nektar and personal fees from GSK, Amgen, Indapta Therapeutics, Sanofi, BMS, CareDx, Kite Pharma, and Karyopharm. B. Dhakal reports receipt of personal fees from Celgene/BMS, Janssen, Amgen, Takeda, GSK, and Sanofi. B. Dholaria reports receipt of institutional research support from Takeda, Janssen, Angiocrine, Pfizer, and Celgene. L.D.A. reports receipt of personal fees from Celgene/BMS, Amgen, GSK, Oncopeptides, Karyopharm, and Janssen. S.G. reports receipt of personal fees and other from Celgene, personal fees and other from Janssen, personal fees and other remuneration from BMS, Sanofi, Actinium, Amgen, Pfizer, GSK, Jazz Pharmaceuticals, and Omeros. S.H. reports recipt of er remuneration from Pfizer, Novartis, Therakos, Janessen, and MSD outside the submitted work., (Copyright © 2021. Published by Elsevier Inc.)