Carfilzomib in combination with lenalidomide and dexamethasone (KRd) did not improve progression-free survival compared with bortezomib, lenalidomide, and dexamethasone (VRd) in patients with newly diagnosed multiple myeloma (MM), and had more toxicity, according to results from a phase 3 trial (Lancet Oncol. 2020;S1470-2045[20]30452-6. doi:10.1016/S1470-2045[20]30452-6).
“[VRd] is a standard therapy for newly diagnosed [MM]. [KRd] has shown promising efficacy in phase 2 trials and might improve outcomes compared with VRd,” explained Shaji Kumar, MD, Mayo Clinic, Rochester, Minnesota and colleagues.
The multicenter, open-label, phase 3 ENDURANCE trial aimed to assess whether KRd is superior to VRd for patients with MM ineligible for immediate autologous stem-cell transplantation (ASCT). Patients were randomized 1:1 to either VRd or KRd for 36 weeks. Patients who completed induction therapy were randomized (1:1) a second time to either indefinite maintenance or 2 years of maintenance with lenalidomide.
The coprimary end points of the trial were progression-free survival (PFS) in the induction phase, and overall survival (OS) in the maintenance phase.
A total of 1087 patients were enrolled in the trial and randomized to VRd (n = 542) or KRd (n = 545). At a median follow-up of 9 months, at a second planned interim analysis, median PFS was 34.6 months in the KRd group compared with 34.4 months in the VRd group (hazard ratio [HR] 1·04, 95% CI 0·83–1·31; P = .74). Median OS was not reached in either group.
The most common grade 3-4 treatment-related non-hematological adverse events were fatigue (34 [6%] of 527 patients in the VRd group versus 29 [6%] of 526 in the KRd group), hyperglycemia (23 [4%] versus 34 [6%]), diarrhea (23 [5%] versus 16 [3%]), peripheral neuropathy (44 [8%] versus 4 [<1%], respectively), dyspnea (9[2%] versus 38 [7%]), and thromboembolic events (11 [2%] versus 26 [5%]).
There were 2 treatment-related deaths reported in the VRd group and 11 in the KRd group.
“The KRd regimen did not improve [PFS] compared with the VRd regimen in patients with newly diagnosed [MM] and had more toxicity,” wrote Dr Kumar and colleagues.
“The VRd triplet regimen remains the standard of care for induction therapy for patients with standard-risk and intermediate-risk newly diagnosed [MM], and is a suitable treatment backbone for the development of combinations of 4 drugs,” they concluded.—Lisa Kuhns
