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 - 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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U2 - 10.1016/j.jtct.2021.10.022
DO - 10.1016/j.jtct.2021.10.022
M3 - Article
C2 - 34781066
AN - SCOPUS:85121149797
SN - 2666-6375
VL - 28
SP - 83.e1-83.e9
JO - Transplantation and Cellular Therapy
JF - Transplantation and Cellular Therapy
IS - 2
ER -