Phase I/II dose expansion of a trial investigating bendamustine and pomalidomide with dexamethasone (BPd) in patients with relapsed/refractory multiple myeloma.
Sivaraj, D; Green, MM; Kang, Y; Rizzieri, D; Diehl, LF; Beaven, AW; Li, Z; Garrett, A; McIntyre, J; Long, GD; Chao, NJA; Gasparetto, C
Published in: Journal of Clinical Oncology
8008 Background: The combination of bendamustine, pomalidomide, and dexamethasone (BPd) displays promising activity in heavily pretreated RRMM. In the Phase I portion, MTD was 120 mg/mbendamustine/3mg pomalidomide/40mg dexamethasone. We report our combined findings from the additional phase II expansion cohort for the first phase I/II trial of BPd in patients with RRMM (NCT01754402). Methods: All patients had to be refractory to prior lenalidomide as well as be pomalidomide naïve, and must have relapsed or have been refractory to their most recent therapy. Treatment consisted of oral pomalidomide PO QD on days 1-21, intravenous (IV) bendamustine given over 30 minutes on day 1, and dexamethasone 40mg on days 1, 8, 15, and 22 of a 28-day cycle. Bendamustine was administered at 120 mg/m for cycle 1, day 1. Results: A total study population of 38 patients was enrolled, with 34 evaluable for toxicity and 32 for efficacy, with 7 patients still receiving treatment. Data cut-off was January 18, 2017. The median age was 67 years, median number of prior regimens was 5, median time from diagnosis was 3.6 years, and median follow-up was 11.7 months. 82% of patients had a prior stem cell transplant, 100% had prior bortezomib, 32% had prior carfilzomib, and all were lenalidomide refractory. Cytogenetic abnormalities included 6 patients with del(17p), 4 with t(4;14), 7 with del(13), and 7 with t(11;14). Patients received a median of 4 cycles of therapy. Best response assessments in 32 evaluable patients showed 3 sCR, 3 VGPR, 17 PR, 7 SD, and 2 PD for an ORR of 72%. The median PFS and OS were 9.6 months and 21.3 months respectively for the entire cohort, with 16 of 32 still alive at follow-up. Grade ≥3 drug-related AEs included fatigue (8%), neutropenia (45%), anemia (26%), thrombocytopenia (24%), and diarrhea (8%). 71% of patients experienced grade ≥3 AEs including neutropenia, anemia, and diarrhea. Conclusions: The BPd regimen is relatively tolerable and achieves a promising overall response rate (ORR of 72%) and durable responses in a heavily pre-treated lenalidomide–refractory population with prior bortezomib exposure, and a median of 5 lines of prior therapy. Clinical trial information: NCT01754402.
