Effect of carfilzomib, lenalidomide, and dexamethasone (KRd) vs lenalidomide and dexamethasone (Rd) in patients with relapsed multiple myeloma (RMM) by line of therapy: Secondary analysis from an interim analysis of the phase III study ASPIRE (NCT01080391).

Background: Previously reported results from ASPIRE (N = 792 patients) showed that KRd significantly improved progression-free survival (PFS) vs Rd in RMM with a favorable benefit-risk profile (Stewart et al. N Engl J Med2015;372:142–52). A secondary analysis of efficacy and safety results from patients treated with KRd or Rd after first relapse (1 prior line of therapy) vs ≥ 2 prior lines of therapy are presented. Methods: Adults with RMM who received 1–3 prior lines were eligible. Patients were randomized (1:1) to KRd or Rd. All patients received lenalidomide (25 mg) on days 1–21 and dexamethasone (40 mg) on days 1, 8, 15, and 22 of a 28-day cycle. Patients in the KRd arm received carfilzomib as a 10-min infusion on days 1, 2, 8, 9, 15, and 16 during cycles 1–12 (20 mg/m² [days 1 and 2 of cycle 1]; 27 mg/m²thereafter). Carfilzomib was omitted on days 8 and 9 during cycles 13–18 and was not administered beyond 18 cycles. Results: Median PFS for patients receiving 1 prior line (n = 341) was 29.6 months (95% confidence interval [CI]: 23.2–33.5) for KRd vs 17.6 months (95% CI: 15.0–22.2) for Rd (hazard ratio [HR]: 0.694; P= .0083). Median PFS for patients receiving ≥ 2 prior lines (n = 451) was 25.8 months (95% CI: 22.2–31.0) for KRd vs 16.7 months (95% CI: 13.9–22.0) for Rd (HR: 0.688; P= .0017). No grade ≥ 3 adverse events (AEs) occurred ≥ 5.0% more frequently with KRd vs Rd in patients who received 1 prior line of therapy; hypokalemia was the only grade ≥ 3 AE that occurred ≥ 5.0% more frequently with KRd (11.0%) vs Rd (3.4%) in patients who received ≥ 2 prior lines. For patients on KRd, neutropenia was the only grade ≥ 3 AE that occurred ≥ 5.0% more frequently after ≥ 2 prior lines (32.4%) vs 1 prior line of therapy (26.4%). Conclusions: The use ofKRd after first relapse led to a 1-year improvement in median PFS vs Rd compared with a 9-month improvement in median PFS vs Rd in pts with ≥ 2 prior lines of therapy, with similar HRs. KRd had a favorable benefit–risk profile after 1 and ≥ 2 prior lines of therapy in patients with RMM. Clinical trial information:NCT01080391

www.asco.org