Carfilzomib or Bortezomib for Triplet Combination Therapy for Multiple Myeloma?

Researchers compared the efficacy of lenalidomide and dexamethasone paired with carfilzomib or bortezomib for the treatment of patients with newly diagnosed multiple myeloma (MM) or those not eligible for autologous hematopoietic cell transplantation (AHCT). They observed no differences in survival between the two cohorts, noting that bortezomib, lenalidomide, and dexamethasone “remains the standard of care for induction therapy for patients with standard- and intermediate-risk newly diagnosed MM.” The results were published in The Lancet Oncology.

The multicenter, open-label, randomized, controlled, phase III ENDURANCE trial included adult patients with newly diagnosed MM who were ineligible for, or did not intend to have, immediate AHCT. Patients were recruited from 272 U.S. community oncology practices or academic medical centers.

Between December 6, 2013, and February 6, 2019, 1,087 patients were randomized 1:1 to receive induction therapy with bortezomib 1.3 mg/m² subcutaneously or intravenously, lenalidomide 25 mg orally, and dexamethasone 20 mg orally (n=542) or carfilzomib 36 mg/m² intravenously, lenalidomide 25 mg orally, and dexamethasone 40 mg orally (n=545) for 36 weeks. Patients who completed induction therapy were then randomized 1:1 again to either indefinite maintenance or two years of maintenance with lenalidomide.

At a median follow-up of nine months (range, 5-23 months), at a second planned interim analysis, the median progression-free survival (PFS; primary endpoint) was 34.6 months (95% confidence interval [CI], 28.8-37.8) in the carfilzomib combination group and 34.4 months (95% CI, 30.1 to not estimable) in the bortezomib combination group (hazard ratio, 1.04; 95% CI, 0.83-1.31; P=0.74). Thus, PFS was not improved with carfilzomib versus standard of care bortezomib, according to the authors. Median overall survival was not reached in either cohort.

The most common grade 3/4 treatment-related non-hematologic adverse events were fatigue (6% in the bortezomib group vs. 6% in the carfilzomib group), hyperglycemia (4% vs. 6%, respectively), diarrhea (5% vs. 3%), peripheral neuropathy (8% vs. <1%), dyspnea (2% vs. 7%), and thromboembolic events (2% vs. 5%).

Treatment-related deaths occurred in two patients (<1%) in the bortezomib group and 11 patients (2%) in the carfilzomib group.