As a progressive disease, multiple myeloma requires continued successive therapies. Because of this, and because patients refractory to anti-CD38 monoclonal antibodies have few treatment options, 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). Belantamab mafodotin treatment resulted in an overall response rate (ORR) of 31% with no new safety signals in a heavily pretreated patient population that was refractory to an immunomodulatory drug and a proteasome inhibitor and were refractory or intolerant to an anti-CD38 antibody. In this analysis of the DREAMM-2 data, 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, and 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%).
ORR was similar for both groups, 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 the median PFS was 2.9 months (95% CI, 1.5-8.3) for the group with 3 to 6 prior therapies and 2.2 months (95% CI, 1.2-3.6) for the group with ≥7 prior therapies. For the group with 3 to 6 therapies, the probability of DOR ≥6 months was 68% (95% CI, 34-87) compared with 72% (95% CI, 41-88) for the group with ≥7 therapies. The probability of PFS at 6 months for the group with 3 to 6 therapies was 38% (95% CI, 23-52) and was 30% (95% CI, 18-44) for the group with ≥7 therapies.
Grade 3/4 adverse events occurring in >10% of the patient population 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 in 96% of patients in the 3 to 6 group and 100% of patients in the ≥7 group; however, most adverse events were managed with dose delays (59% of the group with 3-6 therapies and 49% of the group with ≥7 therapies) and dose reductions (35% of the group with 3-6 therapies and 33% of the group with ≥7 therapies). It was not common for patients to discontinue due to treatment-related adverse events (7% for the 3-6 therapies group and 8% for the ≥7 therapies group).
The authors of this analysis concluded that belantamab mafodotin is an effective and well-tolerated treatment for patients with relapsed/refractory multiple myeloma regardless of their prior treatment subgroup. Both groups had comparable ORR and similar safety profiles. DOR 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.