Carfilzomib, cyclophosphamide, and dexamethasone in patients with newly diagnosed multiple myeloma: a multicenter, phase 2 study.

This multicenter, open-label phase 2 trial determined the safety and efficacy of carfilzomib, a novel and irreversible proteasome inhibitor, in combination with cyclophosphamide and dexamethasone (CCyd) in patients with newly diagnosed multiple myeloma (NDMM) aged ≥65 years or who were ineligible for autologous stem cell transplantation. Patients (N=58) received CCyd for up to nine 28-day cycles, followed by maintenance with carfilzomib until progression or intolerance. After a median of 9 CCyd induction cycles (range 1-9), 95% of patients achieved at least a partial response, 71% achieved at least a very good partial response, 49% achieved at least a near complete response, and 20% achieved stringent complete response. After a median follow-up of 18 months, the 2-year PFS and OS rates were 76% and 87%, respectively. The most frequent grade 3-5 toxicities were neutropenia (20%), anemia (11%), and cardiopulmonary adverse events (7%). Peripheral neuropathy was limited to grade 1-2 (9%). Fourteen percent of patients discontinued treatment owing to adverse events, and 21% of patients required carfilzomib dose reductions. This is the first study of carfilzomib in combination with an alkylating agent in elderly patients with NDMM; results showed high complete response rates and a good safety profile. This study was registered at clinicaltrials.gov, identifier: NCT01346787.