A multicenter, open-label phase II trial found that the selective proteasome inhibitor carfilzomib (Kyprolis), in combination with cyclophosphamide and dexamethasone produced high complete response rates and was associated with low toxicity in patients with newly diagnosed multiple myeloma. “Responses were rapid and deep, and showed improvement over time,” according to the results, published in Blood.
The 58 patients in the trial were all aged ≥ 65 years or were ineligible for autologous stem cell transplantation and enrolled from 10 centers in Italy. Study participants received cyclophosphamide/dexamethasone/carfilzomib for up to nine 28-day cycles, followed by maintenance with carfilzomib until progression or intolerance. A total of 55 patients were evaluable for response, and 56 for safety. The median age of the patients was 71 years.
Major Outcomes
“After a median of 9 [cyclophosphamide/dexamethasone] 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,” according to the investigators.
The median time to achieve a partial response was 1 month, and 94% of patients who achieved a complete response did so during induction. At a median follow-up of 18 months, 2-year progression-free survival was 76% and 2- year overall survival was 87%.
“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%),” the researchers stated. Adverse events led 14% of patients to discontinue treatment and 21% to have the carfilzomib dose reduced. Seven patients died while on the study.
The authors noted that this is the first study of carfilzomib in combination with an alkylating agent in elderly patients with newly diagnosed multiple myeloma. ■
Bringhen S, et al: Blood. May 22, 2014 (early release online).
In the Literature is compiled and written for The ASCO Post by Charlotte Bath.
