Phase 1/2 Dose Expansion of a Trial Investigating Bendamustine and Pomalidomide with Dexamethasone in Patients with RRMM
Bendamustine, an alkylating agent, has demonstrated single-agent activity in approximately 30% of patients with relapsed/refractory multiple myeloma (RRMM). Previous studies have shown that the combination of bendamustine, pomalidomide, and dexamethasone (BPd) shows promising activity in heavily pretreated patients with RRMM. In this phase 1/2, open-label, dose-finding study, the maximum tolerated dose was determined to be 120 mg/m2 of bendamustine, 3 mg of pomalidomide, and 40 mg of dexamethasone (phase 1). The following data report the findings from the phase 2 expansion cohort portion of the phase 1/2 trial of BPd in patients with RRMM.
For study inclusion, all patients were required to be refractory to prior lenalidomide as well as pomalidomide-naïve. Patients were also required to have relapsed or been refractory to their most recent therapy. In this study, patients received oral pomalidomide once daily on days 1 to 21, intravenous bendamustine 120 mg/m2 given over 30 minutes on day 1, and dexamethasone 40 mg on days 1, 8, 15, and 22 of a 28-day treatment cycle.
A total of 38 patients were enrolled in this study. Patients enrolled in the study had a median age of 67 years, median of 5 prior regimens, median of 3.6 years from time of initial diagnosis, and median follow-up of 17.5 months. A total of 82% of patients had a prior stem-cell transplant, 100% had received prior bortezomib therapy, 32% had received prior carfilzomib therapy, and all patients were refractory to lenalidomide.
In the 34 evaluable patients, 3 reported stringent complete responses, 3 reported very good partial responses, and 17 reported partial responses to the therapy combination, resulting in an overall response rate (ORR) of 72%. The median progression-free survival and overall survival were 9.6 months and 21.3 months, respectively, for the entire cohort. The most common grade 3/4 treatment-related adverse events were neutropenia (50%), anemia (29%), and thrombocytopenia (24%).
This study reveals that the BPd combination is relatively tolerable and achieves a promising ORR in a heavily pretreated, lenalidomide-refractory population.
Sivaraj D, et al. ASCO Abstract 8008.