Combining bendamustine, pomalidomide, and dexamethasone achieved a promising overall response rate in patients with heavily pretreated lenalidomide refractory multiple myeloma, according to the results of a phase I/II trial.
Combining bendamustine, pomalidomide, and dexamethasone achieved a promising overall response rate in patients with heavily pretreated lenalidomide-refractory multiple myeloma, according to the results of a phase I/II trial (abstract 8008) presented at the 2017 American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago.
“The overall response rate was 68%, including 18% of patients achieving a very good partial response or better and 9% of patients achieving stringent remission,” said Cristina Gasparetto, MD, of the division of cellular therapy at Duke University Medical Center in Durham, North Carolina.
According to Gasparetto, bendamustine has demonstrated single-agent activity in about 30% of patients with relapsed or refractory disease, and pomalidomide in combination with dexamethasone has activity in about 20% to 30% of patients with lenalidomide-refractory disease.
With this trial, the Gasparetto and colleagues hypothesized that combining bendamustine and pomalidomide with dexamethasone would be highly active in this patient population. The phase I portion of the trial identified a maximum tolerated dose of 120 mg/m2 bendamustine, 3 mg pomalidomide, and 40 mg dexamethasone. This dose was used in a phase II expansion cohort.
The phase II trial included 38 myeloma patients who were refractory to prior lenalidomide and who were pomalidomide-naive. Patients received oral pomalidomide on days 1–21, intravenous bendamustine given over 30 minutes on day 1, and dexamethasone on days 1, 8, 15, and 22 of 28-day cycles. Thirty-four patients were included in the safety analysis and 32 in the efficacy analysis.
The overall response rate was 68%. Three patients achieved stringent complete remission, three achieved very good partial response, 17 (50%) had partial response, one patient had minimal response, and six had stable disease. The clinical benefit rate was 71%.
With a median follow-up of 17.5 months and a median of 8 cycles of therapy, the median progression-free survival was 9.6 months and the median overall survival was 21.3 months.
The researchers also looked at outcomes according to patient genetic risk stratification. There was no significant difference in progression-free or overall survival between those patients with intermediate- or high-risk disease and those with standard-risk disease.
The most commonly occurring hematologic adverse events were anemia (79%), thrombocytopenia (62%), and neutropenia (82%). Common non-hematologic events included fatigue and dyspnea. Five patients had grade 3 pneumonia.