A Multicenter, Open-Label, Phase 1b Study of Carfilzomib, Cyclophosphamide, and Dexamethasone in Newly Diagnosed Multiple Myeloma Patients (CHAMPION-2).

INTRODUCTION: This phase 1b study evaluated the safety and efficacy of 3 dose levels of carfilzomib when provided with fixed dose oral cyclophosphamide and dexamethasone (KCyd) in patients with newly diagnosed multiple myeloma (MM).

PATIENTS AND METHODS: CHAMPION-2 was a multicenter single-arm study. Patients with newly diagnosed secretory MM were enrolled and received KCyd treatment for up to 8 cycles. A 3 + 3 dose escalation scheme was used to evaluate twice-weekly carfilzomib at 36, 45, and 56 mg/m2 dose levels, followed by a dose expansion.

RESULTS: No dose-limiting toxicities were observed in any of the dose evaluation cohorts. The KCyd regimen that included the maximum planned carfilzomib dose of 56 mg/m2 twice weekly was brought forward into dose expansion. A total of 16 patients were treated at this dose level. At 56 mg/m2 the overall response rate was 87.5% (95% confidence interval, 61.7-98.4), and the median time to response of 14 patients whose disease responded to therapy was 1 month. At this dose level, common adverse events of grade 3 or higher were anemia (25.0%), neutropenia (18.8%), acute kidney injury (12.5%), and decreased white blood cell count (12.5%). Ten of 16 patients who received carfilzomib at 56 mg/m2 completed all 8 cycles, 5 patients discontinued study therapy before cycle 8 as a result of adverse events, and 1 patient discontinued therapy as a result of progressive disease.

CONCLUSION: Carfilzomib in combination with cyclophosphamide and dexamethasone is effective and has manageable toxicity for patients with newly diagnosed MM.