Carfilzomib–lenalidomide–dexamethasone vs lenalidomide–dexamethasone in relapsed multiple myeloma by previous treatment

Carfilzomib, a proteasome inhibitor, is approved as monotherapy and in combination with dexamethasone or lenalidomide–dexamethasone (Rd) for relapsed or refractory multiple myeloma. The approval of carfilzomib–lenalidomide–dexamethasone (KRd) was based on results from the randomized, phase 3 study ASPIRE (NCT01080391), which showed KRd significantly improved progression-free survival (PFS) vs Rd (median 26.3 vs 17.6 months; hazard ratio (HR)=0.690; P =0.0001). This subgroup analysis of ASPIRE evaluated KRd vs Rd by number of previous lines of therapy and previous exposure to bortezomib, thalidomide or lenalidomide. Treatment with KRd led to a 12-month improvement in median PFS vs Rd after first relapse (HR 0.713) and a 9-month improvement after ⩾2 previous lines of therapy (HR 0.720). Treatment with KRd led to an approximate 8-month improvement vs Rd in median PFS in bortezomib-exposed patients (HR 0.699), a 15-month improvement in thalidomide-exposed patients (HR 0.587) and a 5-month improvement in lenalidomide-exposed patients (HR 0.796). Objective response and complete response or better rates were higher with KRd vs Rd, irrespective of previous treatment. KRd had a favorable benefit–risk profile and should be considered an appropriate treatment option for patients with 1 or ⩾2 previous lines of therapy and those previously exposed to bortezomib, thalidomide or lenalidomide.