A post-hoc analysis of a pivotal clinical trial presented at ASH 2020 showed that the recently approved belantamab mafodotin-blmf (Blenrep), a first-in-class antibody targeting BCMA (B-cell maturation antigen), induced deep and durable responses in heavily pretreated patients with relapsed or refractory multiple myeloma. This analysis of the ongoing, open-label DREAMM-2 study focused on 1-year outcomes based on the number of previous therapies. The results were presented by Sagar Lonial, MD, FACP, Chief Medical Officer, Winship Cancer Institute, Emory University School of Medicine, Atlanta, GA.
The main results of the DREAMM-2 study, which were presented previously, showed that belantamab monotherapy had deep and durable activity and a manageable safety profile at follow-up of 13 months in heavily pretreated patients with relapsed or refractory multiple myeloma. Based on these results, in August 2020, the FDA approved belantamab for the treatment of patients with relapsed or refractory multiple myeloma who have received at least 4 previous therapies.
Updated Results
The post-hoc analysis presented at the ASH meeting “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,” he added.
“Blenrep therefore represents a useful treatment option for relapsed or refractory multiple myeloma, including patients with a high burden of prior treatment, for whom prognosis is otherwise poor,” Dr Lonial emphasized.
The DREAMM-2 study evaluated belantamab, 2.5 mg/kg or 3.4 mg/kg, administered intravenously every 3 weeks, in patients whose disease was refractory to ≥3 previous lines of therapy, including an immunomodulatory drug and a proteasome inhibitor, and/or refractory to or intolerant of an anti-CD38 monoclonal antibody.
A total of 97 patients received treatment with the recommended 2.5-mg/kg dosage, including 47 patients who had received 3 to 6 previous therapies and 50 patients who had received ≥7 previous lines.
“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,” Dr Lonial said.
The objective response rate—the primary end point—was 34% in patients who had received 3 to 6 previous therapies and 30% in those with ≥7 previous therapies. In the 3 to 6 previous therapies group, 17% of patients had at least a very good partial response and in the more heavily pretreated group, 20% had a very good partial response or better.
The responses were durable in both groups, and the duration of response was 11.0 months in the 3 to 6 previous therapies group and 13.1 months in patients who had received ≥7 previous therapies.
The overall survival was 13.7 months in the 3 to 6 previous lines of therapy group and 13.4 months in the ≥7 previous lines of therapy group. The rates of progression-free survival were 2.9 months and 2.2 months, respectively.
Safety Profile
The safety profile of belantamab was similar in both groups.
The most common adverse events were similar across the 2 subgroups, including ocular events. The rate of anemia was higher in the more heavily pretreated subgroup than in those who received 3 to 6 previous lines of therapy (31% vs 17%).
The most common grade 3 or 4 adverse events in the 3 to 6 and ≥7 previous lines of therapy groups, respectively, were keratopathy (33% vs 27%), thrombocytopenia (17% vs 20%), anemia (11% vs 31%), and decreased lymphocyte count (11% vs 14%).
Across both subgroups, adverse events were managed with dose delays in 59% of patients who received 3 to 6 lines of therapy and 49% in those who received ≥7 lines of treatment. Treatment discontinuation because of treatment-related adverse events was uncommon (7% and 8%, respectively).