TY - JOUR
T1 - Impact of Induction Therapy with VRD versus VCD on Outcomes in Patients with Multiple Myeloma in Partial Response or Better Undergoing Upfront Autologous Stem Cell Transplantation
AU - Sidana, Surbhi
AU - Kumar, Shaji
AU - Fraser, Raphael
AU - Estrada-Merly, Noel
AU - Giralt, Sergio
AU - Agrawal, Vaibhav
AU - Anderson, Larry D.
AU - Aljurf, Mahmoud
AU - Banerjee, Rahul
AU - Bashey, Asad
AU - Battiwalla, Minoo
AU - Beitinjaneh, Amer
AU - Chakraborty, Rajshekhar
AU - Chhabra, Saurabh
AU - Dhakal, Binod
AU - Dholaria, Bhagirathbhai
AU - Hashmi, Shahrukh
AU - Janakiram, Murali
AU - Lee, Cindy
AU - Lekakis, Lazaros
AU - Murthy, Hemant S.
AU - Parrondo, Ricardo
AU - Wangjam, Tamna
AU - Usmani, Saad
AU - Shah, Nina
AU - Qazilbash, Muzaffar
AU - D'Souza, Anita
N1 - Funding Information:
Financial disclosure: This study was funded through the CIBMTR. S.S. was supported by the KL2 Mentored Career Development Program (KL2TR003143). The CIBMTR is supported primarily by Public Health Service Grant U24CA076518 from the National Cancer Institute (NCI), the National Heart, Lung and Blood Institute (NHLBI), and the National Institute of Allergy and Infectious Diseases (NIAID); Grant U24HL138660 from the NHLBI and NCI; Grants OT3HL147741 and U01HL128568 from the NHLBI; Grants HHSH250201700006C and HHSH250201700007C from the Health Resources and Services Administration (HRSA); and Awards N00014-20-1-2705 and N00014-20-1-2832 from the Office of Naval Research. Additional federal support is provided by Grants P01CA111412, R01CA152108, R01CA215134, R01CA218285, R01CA231141, R01AI128775, R01HL126589, R01HL129472, R01HL130388, R01HL131731, U01AI069197, U01AI126612, and UG1HL06924 and the Biomedical Advanced Research and Development Authority. Support is also provided by Be the Match Foundation, Boston Children's Hospital, Dana Farber, St. Baldrick's Foundation, Stanford University, Medical College of Wisconsin, National Marrow Donor Program, and from the following commercial entities: Actinium Pharmaceuticals, Adienne SA, AlloVir, Amgen, Angiocrine Bioscience, Astellas Pharma US, bluebird bio, Bristol Myers Squibb, Celgene, CSL Behring, CytoSen Therapeutics, Daiichi Sankyo, ExcellThera, Fate Therapeutics, Gamida Cell, Genentech, Incyte, Janssen/Johnson & Johnson, Jazz Pharmaceuticals, Kiadis Pharma, Kite Pharma, Kyowa Kirin, Legend Biotech, Magenta Therapeutics, Merck Sharp & Dohme, Millennium, Miltenyi Biotec, Novartis Pharmaceuticals, Omeros, Oncoimmune, Orca Biosystems, Pfizer, Pharmacyclics, Sanofi Genzyme, Stemcyte, Takeda Pharma, Vor Biopharma, and Xenikos BV. The views expressed in this article do not reflect the official policy or position of the NIH, Department of the Navy, Department of Defense, HRSA, or any other agency of the US Government.
Funding Information:
Financial disclosure: This study was funded through the CIBMTR. S.S. was supported by the KL2 Mentored Career Development Program (KL2TR003143). The CIBMTR is supported primarily by Public Health Service Grant U24CA076518 from the National Cancer Institute (NCI), the National Heart, Lung and Blood Institute (NHLBI), and the National Institute of Allergy and Infectious Diseases (NIAID); Grant U24HL138660 from the NHLBI and NCI; Grants OT3HL147741 and U01HL128568 from the NHLBI; Grants HHSH250201700006C and HHSH250201700007C from the Health Resources and Services Administration (HRSA); and Awards N00014-20-1-2705 and N00014-20-1-2832 from the Office of Naval Research. Additional federal support is provided by Grants P01CA111412, R01CA152108, R01CA215134, R01CA218285, R01CA231141, R01AI128775, R01HL126589, R01HL129472, R01HL130388, R01HL131731, U01AI069197, U01AI126612, and UG1HL06924 and the Biomedical Advanced Research and Development Authority. Support is also provided by Be the Match Foundation, Boston Children's Hospital, Dana Farber, St. Baldrick's Foundation, Stanford University, Medical College of Wisconsin, National Marrow Donor Program, and from the following commercial entities: Actinium Pharmaceuticals, Adienne SA, AlloVir, Amgen, Angiocrine Bioscience, Astellas Pharma US, bluebird bio, Bristol Myers Squibb, Celgene, CSL Behring, CytoSen Therapeutics, Daiichi Sankyo, ExcellThera, Fate Therapeutics, Gamida Cell, Genentech, Incyte, Janssen/Johnson & Johnson, Jazz Pharmaceuticals, Kiadis Pharma, Kite Pharma, Kyowa Kirin, Legend Biotech, Magenta Therapeutics, Merck Sharp & Dohme, Millennium, Miltenyi Biotec, Novartis Pharmaceuticals, Omeros, Oncoimmune, Orca Biosystems, Pfizer, Pharmacyclics, Sanofi Genzyme, Stemcyte, Takeda Pharma, Vor Biopharma, and Xenikos BV. The views expressed in this article do not reflect the official policy or position of the NIH, Department of the Navy, Department of Defense, HRSA, or any other agency of the US Government. The CIBMTR supports accessibility of research in accordance with the National Institutes of Health's Data Sharing Policy and the National Cancer Institute's Cancer Moonshot Public Access and Data Sharing Policy. The CIBMTR releases only deidentified datasets that comply with all relevant global regulations regarding privacy and confidentiality.
Funding Information:
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.
Publisher Copyright:
© 2021
PY - 2022/2
Y1 - 2022/2
N2 - 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/m2) 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.
AB - 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/m2) 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.
KW - Induction therapy
KW - Multiple myeloma
KW - Upfront transplant
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UR - http://www.scopus.com/inward/citedby.url?scp=85121149797&partnerID=8YFLogxK
U2 - 10.1016/j.jtct.2021.10.022
DO - 10.1016/j.jtct.2021.10.022
M3 - Article
C2 - 34781066
AN - SCOPUS:85121149797
VL - 28
SP - 83.e1-83.e9
JO - Transplantation and Cellular Therapy
JF - Transplantation and Cellular Therapy
SN - 2666-6375
IS - 2
ER -