Belantamab mafodotin plus pembrolizumab resulted in a more favorable overall response rate (ORR) compared with single-agent belantamab mafodotin in heavily pre-treated relapsed/refractory multiple myeloma (MM), according to the DREAMM-4 study. The results were presented at the 2022 ASCO Annual Meeting.
Belantamab mafodotin is a B-cell maturation antigen (BCMA) targeted antibody drug conjugate approved for adult patients with relapsed/refractory MM.
The phase I/II, single-arm, open-label DREAMM-4 study assessed the safety and clinical activity of belantamab mafodotin plus pembrolizumab in adults with relapsed/refractory MM who had received three or more prior lines of therapy, including an anti-CD38 monoclonal antibody, proteasome inhibitor, and immunomodulator. Part 1 of the study established the recommended part 2 treatment dose: belantamab mafodotin 2.5 mg/kg and pembrolizumab 200 mg, both administered intravenously every three weeks for up to 35 cycles.
As of October 18, 2021, 34 patients were treated: six in part 1 and 28 in part 2. Patients had received a median of five prior lines of therapy (range, 3-13 lines of therapy). Ten patients (29%) had high-risk cytogenetics, and nine (26%) had extramedullary disease.
After a median follow-up of 14.7 months, the ORR (primary endpoint) for this treatment combination was 47% (n=10). See TABLE 1 for all response outcomes. The median duration of response was eight months (95% CI, 2.1-not reached). Median progression-free survival was 3.4 months (95% CI, 1.4-5.6).
Most patients experienced at least one adverse event (97% any-grade adverse events), including 74% who experienced grade ≥3 adverse events. The most common (≥35%) any-grade and grade 3 adverse events were keratopathy (76% and 38%), blurred vision (38% and 0%), and thrombocytopenia (35% and 29%). Nine patients had serious adverse events, and four patients had one or more treatment-related serious adverse events. Two patients had grade 1 immune-related reactions (gout and autoimmune hypothyroidism). Treatment-related dose delays (65%) and reductions (32%) occurred, but no patients discontinued treatment due to adverse events.
Preliminary pharmacokinetic and soluble BCMA data were consistent with single-agent belantamab mafodotin therapy. The authors noted that future studies will pursue other treatment combinations with belantamab mafodotin.
The study was funded by GSK in collaboration with Merck Sharpe & Dohme LLC, a subsidiary of Merck & Co., Inc.
Suvannasankha A, Bahlis NJ, Trudel S, et al. Safety and clinical activity of belantamab mafodotin with pembrolizumab in patients with relapsed/refractory multiple myeloma (RRMM): DREAMM-4 Study. Abstract #8018. Presented at the 2022 American Society of Clinical Oncology Annual Meeting, June 3-7, 2022.