KRD vs. VRD as induction before autologous hematopoietic progenitor cell transplantation for high-risk multiple myeloma

Bone Marrow Transplant. 2022 Jul;57(7):1142-1149. doi: 10.1038/s41409-022-01697-4. Epub 2022 May 6.

Abstract

Bortezomib, lenalidomide, and dexamethasone (VRD) induction is standard prior to autologous hematopoietic cell transplantation (auto-HCT) in newly diagnosed, high-risk multiple myeloma (ND-HRMM). Carfilzomib (K) is another proteasome inhibitor approved for MM. In this single-center, retrospective analysis, we compared outcomes in ND-HRMM with pre-transplant KRD or VRD induction. High-risk was defined by t(4:14), t(14:16), 1q21 gain/amplification, or del(17p). Primary endpoints were progression-free (PFS) and overall survival (OS). Of 121 ND-HRMM patients, 63 received KRD, and 58 received VRD. Post-induction, complete (CR), very good partial (VGPR), partial response (PR), and overall response (ORR) rates were 23.8%/49.2%/25.4%/98.4% with KRD, and 19%/46.6%/27.6%/93.1% with VRD. At day 100 post-auto-HCT, these were 38.1%/42.9%/19%/100% with KRD, versus 35.1%/49.1%/12.3%/94.8% with VRD. Pre-auto-HCT, 11 (18.3%) KRD and 7 (12.5%) VRD patients had minimal residual disease (MRD)-negative CR (p = 0.45). Post-auto-HCT, 14 (41.2%) and 13 (43.3%) patients had MRD-negative CR (p = 1.000). Median PFS was 38.2 (95%CI 28.7-NA) and 45.9 months (95%CI 43.2-NA) for KRD and VRD, respectively (p = 0.25). Respective 3-year PFS and OS were 53.5% (95%CI 41.1-69.6) and 95.2% (95%CI 90-100) for KRD and 64% (95%CI 51.6-79.5) and 84.2% (95%CI 73.5-96.3, p = 0.30) for VRD. Overall, KRD induction pre-auto-HCT does not improve outcomes. Prospective, randomized studies are needed to confirm these findings.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Combined Chemotherapy Protocols* / therapeutic use
  • Bortezomib / therapeutic use
  • Chromosome Aberrations*
  • Dexamethasone / therapeutic use
  • Hematopoietic Stem Cell Transplantation*
  • Humans
  • Lenalidomide / therapeutic use
  • Multiple Myeloma* / genetics
  • Multiple Myeloma* / therapy
  • Oligopeptides / therapeutic use
  • Retrospective Studies
  • Translocation, Genetic
  • Transplantation, Autologous

Substances

  • Oligopeptides
  • Bortezomib
  • carfilzomib
  • Dexamethasone
  • Lenalidomide