Seeking the Right Dose of Immunoconjugate Combination in Resistant Myeloma
Posted: Friday, January 29, 2021
Work continues in finding the recommended phase II dose of belantamab mafodotin to be used in combination with pomalidomide and dexamethasone in patients with relapsed or refractory multiple myeloma. The first results of the dose-escalating/dose-finding phase I study, involving data regarding 29 evaluable patients at a median follow-up of 6 months, were presented during the 2020 American Society of Hematology (ASH) Annual Meeting and Exposition (Abstract 725) by Suzanne Trudel, MD, MSc, FRCPC, of the University of Toronto’s Princess Margaret Cancer Centre, and colleagues.
Belantamab mafodotin is a first-in-class immunoconjugate targeting B-cell maturation antigen; it previously showed activity and a manageable safety profile in patients with multiple myeloma. Pomalidomide—with which the immunoconjugate should work well, the investigators believe—augments T-cell– and natural killer cell–mediated immunity. The participants in this trial (median age, 64 years) all had received two or more prior lines of treatment, had been exposed to lenalidomide and a proteasome inhibitor, and were refractory to their last line of therapy.
So far, the combination has shown “promising efficacy,” noted Dr. Trudel and colleagues, with treatment-emergent adverse events consistent with the known safety profiles of both drugs. Across all cohorts, the overall response rate was 86.2%, including 6 partial responses, 15 very good partial responses, and 4 stringent complete responses. In addition, median progression-free survival has not been reached in any of the treatment groups.
The 35 patients originally enrolled were divided into various belantamab mafodotin dose levels and schedules. Ultimately, the maximum tolerated dose of belantamab mafodotin was determined to be 2.5 mg/kg “single” (given in full on day 1 of the cycle) or 2.5 mg/kg “split” (divided and given equally on days 1 and 8 of the cycle).
“However, the high rate of dose holds at the 2.5-mg/kg dose has prompted exploration of alternative dosing schedules,” concluded the researchers. Therefore, “the recommended phase II dose selection is pending completion of the current cohorts.”
Disclosure: The study authors’ disclosure information can be found ash.confex.com.
