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.

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.