The randomized phase 3 ENDEAVOR study demonstrated that the carfilzomib plus dexamethasone (Kd) regimen significantly prolonged progression-free survival (PFS) compared with the bortezomib plus dexamethasone (Vd) combination, with a near doubling of median PFS (18.7 months vs 9.4 months) and a nearly 50% reduction in risk of progression in relapsed multiple myeloma (RMM).1,2 Moreau and colleagues presented a subgroup analysis of the impact of prior treatment (ie, after first relapse, ?2 prior lines of therapy), and prior exposure to bortezomib or lenalidomide, on efficacy and safety of Kd and Vd treatment.3 In the ENDEAVOR trial, 929 patients were randomized to Kd–carfilzomib (30-minute intravenous infusion) plus dexamethasone 20 mg (n = 464), or Vd–bortezomib 1.3 mg/m2 (intravenously or subcutaneously) plus dexamethasone 20 mg (n = 465). Patients with RMM who received Kd therapy showed significant PFS improvements regardless of the number of prior lines of therapy compared with Vd therapy (1 prior line: 22.2 months vs 10.1 months; ?2 prior lines: 14.9 months vs 8.4 months); patients who received 1 prior line of therapy derived the most PFS benefit. In addition, PFS benefit with Kd versus Vd was achieved regardless of prior exposure to bortezomib (prior bortezomib exposure: 15.6 months vs 8.1 months; no prior bortezomib exposure: not estimated vs 11.2 months) or lenalidomide (prior lenalidomide exposure: 12.9 months vs 7.3 months; no prior lenalidomide exposure: 22.2 months vs 10.2 months). Similarly, patients treated with Kd showed higher overall response rates than those treated with Vd irrespective of previous lines of therapy or exposure to bortezomib or lenalidomide. The rates of grade 3/4 adverse events were slightly higher with Kd therapy in both prior treatment subgroups compared with the Vd group, but rates of grade ?2 peripheral neuropathy were lower. Grade ?3 hypertension, dyspnea, and cardiac failure occurred more frequently with Kd therapy. The authors concluded that Kd therapy had a favorable benefit–risk profile in RMM, irrespective of the number of prior therapy lines and prior exposure to bortezomib or lenalidomide.
