Because multiple myeloma is a progressive disease and requires continued successive therapies, and there are few treatment options for patients who are refractory to anti-CD38 monoclonal antibodies, new therapies are needed.
The DREAMM-2 study evaluated one such therapy: the investigational agent belantamab mafodotin (belamaf, GSK2857916; B-cell maturation antigen–targeting immunoconjugate). In a heavily pretreated patient population that was refractory to an immunomodulatory drug and a proteasome inhibitor and refractory or intolerant to an anti-CD38 antibody, treatment with belantamab mafodotin resulted in an overall response rate (ORR) of 31% with no new safety signals. Based on data from the DREAMM-2 analysis, safety, tolerability, and clinical activity of belantamab mafodotin were assessed for subgroups of patients with differing numbers of prior therapies.
For the DREAMM-2 study, the primary end point was ORR; other important end points included duration of response (DOR), progression-free survival (PFS), overall survival, and safety. For this analysis, 97 patients were separated into 2 subgroups: those who had 3 to 6 prior therapies (47 patients, 48%) and those with ≥7 prior therapies (50 patients, 52%).
For both groups, ORR rates were similar: 32% (97.5% confidence interval [CI], 17.6-49.2) for patients with 3 to 6 prior therapies and 30% (97.5% CI, 16.5-46.6) for patients with ≥7 prior therapies. For the subgroup with 3 to 6 prior therapies, 8 patients had very good partial response or better (53% of responders) compared with 10 patients in the subgroup with ≥7 prior therapies (67% of responders). The DOR was not reached for either subgroup, and median PFS rates were 2.9 months (95% CI, 1.5-8.3) and 2.2 months (95% CI, 1.2-3.6) for the groups with 3 to 6 and ≥7 prior therapies, respectively. The probability rates of DOR ≥6 months were 68% (95% CI, 34-87) and 72% (95% CI, 41-88) for the groups with 3 to 6 and ≥7 therapies, respectively. At 6 months, the PFS probability rates were 38% (95% CI, 23-52) and 30% (95% CI, 18-44) for the groups with 3 to 6 and ≥7 therapies, respectively.
In >10% of the patient population, grade 3/4 adverse events occurring were keratopathy (3-6 group, 33%; ≥7 group, 27%), thrombocytopenia (3-6 group, 15%; ≥7 group, 20%), anemia (3-6 group, 9%; ≥7 group, 31%), and decreased lymphocyte count (3-6 group, 11%; ≥7 group, 14%). Adverse events occurred in 96% and 100% of patients in the 3 to 6 and ≥7 groups, respectively; however, most adverse events were managed with dose delays (59% and 49% of the groups with 3-6 and ≥7 therapies, respectively) and dose reductions (35% and 33% of the groups with 3-6 and ≥7 therapies, respectively). Patients typically did not discontinue therapy due to treatment-related adverse events (7% and 8% of the groups with 3-6 and ≥7 therapies, respectively).
The authors concluded that belantamab mafodotin is an effective and well-tolerated treatment for patients with relapsed/refractory multiple myeloma (RRMM) regardless of patients’ prior treatment subgroup. Both groups had comparable ORR and similar safety profiles. DOR rates will be updated at a later time.
Reference
Abstract and Poster EP937. EHA 2020. June 12, 2020. DREAMM-2: single-agent belantamab mafodotin in patients with relapsed/refractory multiple myeloma (RRMM) – outcomes by prior therapies.