Background: A combination therapy of carfilzomib, bendamustine and dexamethasone (KBd) was evaluated in this multicenter phase 1/2 trial conducted within the European Myeloma Network (EMN09 trial).
Methods: Sixty-three relapsed/refractory multiple myeloma (RRMM) patients with ≥2 lines of prior therapy were included. The phase 1 portion of the study determined the maximum tolerated dose (MTD) of carfilzomib with bendamustine set at 70 mg/m2 at days 1 and 8. After 8 cycles responding patients received maintenance therapy with carfilzomib and dexamethasone until progression.
Results: Based on the phase 1 results, the recommended phase 2 dose for carfilzomib was 27 mg/m2 twice weekly weeks 1 to 3. 52% of patients achieved ≥PR with 30% reaching ≥VGPR. The clinical benefit rate was 93%. After a median follow-up of 21.9 months, the median PFS was 11.6 months and the median OS 30.4 months. Grade ≥3 hematological adverse events (AEs) were lymphopenia (29%), neutropenia (25%) and thrombocytopenia (22%). Main non-hematological AEs grade ≥3 were pneumonia, thromboembolic events (10%), cardiac AEs (6%) and hypertension in (2%).
Conclusion: In heavily pre-treated RRMM patients the KBd combination is an effective, treatment option, administered in the outpatient setting. Infection prophylaxis and attention to patients with cardiovascular predisposition are required. Clinicaltrials.gov identifier: NCT02056756