A post-hoc analysis of a pivotal clinical trial showed that belantamab mafodotin-blmf (Blenrep), a first-in-class antibody–drug conjugate targeting B-cell maturation antigen, induced deep and durable responses in heavily pretreated patients with relapsed or refractory multiple myeloma.
The new analysis of the ongoing, open-label DREAMM-2 trial, focusing on 1-year outcomes according to the number of previous therapies, was presented by Sagar Lonial, MD, FACP, Chief Medical Officer, Winship Cancer Institute, Emory University School of Medicine, Atlanta, GA, at the virtual 2020 ASH Annual Meeting.
Results from DREAMM-2, presented previously, showed that single-agent belantamab mafodotin had deep and durable clinical activity and a manageable safety profile with follow-up to 13 months in heavily pretreated patients with relapsed or refractory multiple myeloma. Based on these results, in August 2020, the FDA approved belantamab mafodotin for the treatment of patients with relapsed or refractory multiple myeloma who have received at least 4 previous therapies.
The post-hoc analysis presented at ASH 2020 showed that “the efficacy and safety was not affected by the number of prior therapies,” said Dr Lonial. “Blenrep achieved deep and durable responses, with no notable alterations in its safety profile, even when patients had received 7 or more prior lines of therapy.”
“Blenrep therefore represents a useful treatment option for relapsed/refractory multiple myeloma, including patients with a high burden of prior treatment, for whom prognosis is otherwise poor,” he added.
Investigators in the DREAMM-2 trial evaluated belantamab mafodotin (2.5 mg/kg or 3.4 mg/kg administered intravenously every 3 weeks) in patients who were refractory to at least 3 previous lines of therapy including an immunomodulatory drug and a proteasome inhibitor and/or were intolerant to an anti-CD38 monoclonal antibody.
The cohort treated with the recommended 2.5-mg/kg dose consisted of 97 patients; 47 of these patients had received 3 to 6 previous therapies and 50 had received ≥7 previous therapies.
“All patients across both groups were triple-refractory, that is, refractory to at least 1 therapy from each of the immunomodulatory, proteasome inhibitor, and monoclonal antibody drug classes of therapy,” said Dr Lonial.
The objective response rate, the primary end point, was 34% in patients with 3 to 6 previous therapies and 30% in those with ≥7 previous therapies. In the group with 3 to 6 previous therapies, 17% had at least a very good partial response (VGPR) and in the more heavily pretreated group, 20% had VGPR or better. Responses were durable in both groups, with durations of response of 11.0 months in the group with 3 to 6 previous lines and 13.1 months in those with ≥7 previous therapies.
Overall survival was 13.7 months in patients with 3 to 6 previous lines of therapy and 13.4 months in patients with ≥7 previous lines of therapy. Progression-free survival rates were 2.9 months and 2.2 months, respectively.
The safety profile of belantamab mafodotin was similar in both groups, with comparable rates of adverse events, serious adverse events, dose modifications, and low rates of treatment discontinuation. The most common adverse events were largely similar across the 2 subgroups, including ocular events. The rate of anemia was higher in the more heavily treated patients than in those treated with 3 to 6 previous lines of therapy (31% vs 17%).
The most common grade 3/4 adverse events in the subgroups treated with 3 to 6 and ≥7 previous lines, respectively, were keratopathy (33% vs 27%), thrombocytopenia (17% vs 20%), anemia (11% vs 31%), and decreased lymphocyte count (11% vs 14%).
Adverse events were managed with dose delays and reductions; discontinuations related to treatment-related adverse events were uncommon.