Carfilzomib is an irreversible and selective proteasome inhibitor with antiproliferative and proapoptotic activities.
Kyprolis is available as a 50ml vial containing 60mg carfilzomib powder for solution for infusion (2mg/ml after reconstitution). It is administered as a 10-minute intravenous infusion on two consecutive days each week for three weeks (days 1, 2, 8, 9, 15 and 16), followed by a 12-day rest period (days 17-28). Each 28-day period comprises one treatment cycle. From cycle 13, the day 8 and 9 doses of Kyprolis are omitted. The starting dose is 20mg/m2 on days 1 and 2 of cycle 1, increasing to 27mg/m2 (max 60mg) on day 8 of cycle 1 if tolerated.
The randomised, open-label ASPIRE study compared carfilzomib plus lenalidomide and dexamethasone with lenalidomine and dexamethasone alone (control group) in 792 patients with relapsed multiple myeloma.
Carfilzomib treatment was administered for a maximum of 18 cycles unless discontinued early for disease progression or unacceptable toxicity.
Progression-free survival (PFS, primary endpoint) was significantly greater in patients treated with carfilzomib with a median PFS of 26.3 months vs 17.6 months in the control group (hazard ratio for progression or death 0.69 [95% CI 0.57–0.83; p<0.0001]).