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

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.

Impact of Induction With VCD Versus VRD on the Outcome of Patients With Multiple Myeloma After an Autologous Hematopoietic Stem Cell Transplantation.

Induction therapy with a triplet regimen, followed by high-dose therapy and autologous hematopoietic stem cell transplantation (auto-HCT), is the standard of care for newly diagnosed, transplant-eligible patients with multiple myeloma (MM). Bortezomib-dexamethasone with cyclophosphamide (VCD) or lenalidomide (VRD) are the most used induction regimens. However, previous studies comparing VCD and VRD showed disparate results. The goal of this retrospective study was to compare the "real-world" results of VCD and VRD in transplant-eligible MM patients outside of a clinical trial. We identified 322 patients who received VRD or VCD induction before auto-HCT at our institution. All patients received melphalan conditioning and single-agent lenalidomide maintenance therapy. Overall, 114 patients received VCD, and 208 received VRD. The median age at auto-HCT was 61.9 years (range 33.9-79.6), with 35.4% (114/322) of the cohort being 65 years of age or older. The overall response rate was 99.7% after auto-HCT, with a significantly lower complete remission rate as the final response in the VCD compared to the VRD group (34% versus 53%; P = .001). However, there was no significant difference between the best response rate of very good partial response (VGPR) or better in the VCD compared to the VRD group (92% versus 85%; P = .078). The median duration of ≥VGPR was 50.0 months (95% confidence interval [CI], 42.0-69.1) for both cohorts, and there was no difference between VCD and VRD (P = .769; hazard ratio, 0.95; 95% CI, 0.69-1.31). Median follow-up of survivors was 73 months. There was no difference in the relapse rate between VCD and VRD (P = .749). Median progression-free survival (PFS) was 48.7 months in the VCD and 44.6 months in the VRD group (P = .858). Median overall survival (OS) was 103.8 months with VCD and 101.7 months with VRD (P = .891). At 5 years, the PFS and OS were 38.1% and 76.9% for the VCD group, respectively, and 40.7% and 74.6% for the VRD group, respectively. On multivariate analysis for OS in the entire cohort, Revised International Staging System I and post-auto-HCT best response of stringent complete response (sCR)/CR emerged as significant predictors of superior OS. There was no impact of the type of induction regimen on the OS in the multivariate analysis. Induction therapy with VCD compared to VRD was associated with a lower CR rate, but there was no difference in PFS or OS between the 2 regimens.

Real-world long-term outcomes in multiple myeloma with VRD induction, Mel200-conditioned auto-HCT, and lenalidomide maintenance.

Standard-of-care for newly-diagnosed, autologous hematopoietic stem cell transplantation (auto-HCT)-eligible, multiple myeloma (MM) patients includes bortezomib, lenalidomide, and dexamethasone (VRD) induction followed by melphalan 200 mg/m2 (Mel200)-conditioned auto-HCT and lenalidomide maintenance. We completed a retrospective case series assessing outcomes of 187 MM patients who received this regimen at our institution. The 100-day non-relapse mortality incidence was zero. Before auto-HCT, 9.6 and 52.9% of patients achieved a complete response (CR) or ≥ very good partial response (VGPR), respectively. At day-100 post-transplant, 29.4 and 74.9% had achieved a CR/stringent-CR (sCR) or ≥ VGPR, respectively. At the last evaluation, 57.2% of patients had CR/sCR and 87.1% had ≥ VGPR. Median follow-up, progression-free survival (PFS), and overall survival (OS) were 63.2, 50, and 101.7 months, respectively. The 5-year PFS and OS were 43.1 and 79%. High-risk cytogenetics was associated with worse outcomes. This study illustrates that VRD induction, Mel200-conditioned auto-HCT, and lenalidomide maintenance are associated with good outcomes in MM.