Carfilzomib, lenalidomide, and dexamethasone (KRd) versus bortezomib, lenalidomide, and dexamethasone (VRd) induction prior to autologous haematopoietic stem cell transplant/transplantation in newly diagnosed multiple myeloma

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Abstract
Summary: Bortezomib, lenalidomide and dexamethasone (VRd) and carfilzomib, lenalidomide and dexamethasone (KRd) regimens have been widely used for induction in transplant‐eligible newly diagnosed multiple myeloma (NDMM), yet direct comparisons between these regimens have been limited and inconsistent. We retrospectively analysed 1129 NDMM patients who received KRd ( n = 364) or VRd ( n = 765) before upfront autologous haematopoietic stem cell transplantation at a single‐centre between 2006 and 2021. KRd‐treated patients more often had high‐risk cytogenetics and advanced Second revision of the International Staging System (R2‐ISS) stage. Pretransplant complete response (CR) and ≥very good partial response (VGPR) rates were higher with KRd (23% and 71%) than VRd (16% and 61%; p = 0.002), with superior best post‐transplant ≥CR (71% vs. 60%; p = 0.001) and higher pretransplant measurable residual disease (MRD) negativity (49% vs. 42%; p = 0.027). After a median follow‐up of 38.6 months, median progression‐free survival (PFS) was 62.2 versus 48.7 months (hazard ratio [95% confidence interval] 0.74 [0.59–0.93], p = 0.009) and median overall survival (OS) was not reached versus 122.7 months (0.86 [0.59–1.25], p = 0.43) for KRd and VRd respectively. In inverse probability–weighted multivariable analysis, KRd remained associated with improved PFS (0.76 [0.60–0.97], p = 0.025), with no OS difference. The PFS benefit was most pronounced in standard‐risk, younger and male patients, and those with fewer comorbidities. Overall, KRd induction led to deeper responses and improved PFS compared with VRd.
Funding Information
  • National Cancer Institute (P30 CA016672)
  • Dr. Miriam and Sheldon G. Adelson Medical Research Foundation
  • Paula and Rodger Riney Foundation
  • Leukemia and Lymphoma Society (SCOR‐12206‐17)
  • University of Texas MD Anderson Cancer Center

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