Real-world study of the efficacy and safety of belantamab mafodotin (GSK2857916) in relapsed or refractory multiple myeloma based on data from the nominative ATU in France: the IFM 2020-04 study

Abstract

Belantamab mafodotin (BM) is an anti-BCMA antibody-drug conjugate (GSK2857916) that represents an alternative option in multiple myeloma. We sought to assess the efficacy and safety in real-world of BM in patients who benefited from an early access program. We conducted an observational, retrospective, multicenter study. Eligibility criteria were treatment of relapsed or refractory multiple myeloma (RRMM) in monotherapy in adult patients who have received at least 3 lines of therapy previously, including at least one immunomodulatory agent (IMiD), a proteasome inhibitor (PI) and an anti-CD38 monoclonal antibody, and whose disease progressed during the last treatment period. The primary endpoint of the study is to assess the overall survival (OS). The trial was sponsored by the French group IFM and supported by GSK. Between November 2019 and December 2020, 106 patients were treated with BM; 97 were eligible for the efficacy evaluation and 104 for safety. The median age was 66 (range: 37–82) years. High risk cytogenetics were identified in 40.9% of patients. Fifty-five (56.7%) patients were triple-class refractory and 11 (11.3%) were penta-class refractory. The median number of prior lines of treatment was 5 (range: 3–12). The median number of BM cycles administered was 3 (range: 1–22). The overall response rate at best response was 38.1% (37/97). The median OS was 9.3 months (95%CI: 5.9; 15.3), and median progression-free survival was 3.5 months (95%CI: 1.9; 4.7). The median duration of response was 9 months (range 4.65-10.4). Treatment was delayed for 55 (52.9%) patients including 36.5% for treatment-related toxicity. Ophthalmic adverse events, mainly grade ≤2, were the most common toxicity (48%). The occurrence of keratopathy was 37.5%. Overall, our data are concordant with the results from DREAMM-2 in terms of efficacy and safety on a non-biased population.

Real-World Effectiveness and Safety of Belantamab Mafodotin Monotherapy in Triple-Class Refractory Multiple Myeloma

“…The survival outcomes were more favorable for the responders, most of whom had sustained disease control and long-term remission. Accumulating evidence from real-world studies is in accordance with our results (Table 2) [14][15][16][17][18][19]. A multicenter Italian study had a comparable cohort size (n = 28) to our study and reported an ORR of 40% and comparable survival outcomes [15].…”

“…A multicenter Italian study had a comparable cohort size (n = 28) to our study and reported an ORR of 40% and comparable survival outcomes [15]. In France, the IFM reported the outcomes of the compassionate use program of belantamab mafodotin including 97 patients with a median of five prior lines of therapies [17]. However, only 56% of the patients were triple-class refractory in this cohort.…”

“…Approximately one third of our patients experienced keratopathy due to belantamab mafodotin administration. Reported rates of keratopathy vary slightly among real-world studies and the DREAMM-2 clinical trial range is from 32% to 72% [5,6,[14][15][16][17][18]. This may be attributed to differences in the clinical practice and ophthalmological expertise in different clinical settings, as well as the robustness of adverse event reporting between clinical trials and real-world studies [9].…”

“…Ocular adverse events are the hallmark of belantamab mafodotin-related toxicities. Keratopathy and decrease in best corrected visual acuity (BCVA) may lead to treatment delays or even discontinuation in up to one fifth of the patients [14][15][16][17][18][19]. It seems that the rate of treatment discontinuation due to keratopathy is greater in real-world clinical practice than the DREAMM-2 study, in which only three patients discontinued due to corneal events [6,24].…”

The Gaining Momentum of BCMA-Directed Therapies for Relapsed/Refractory Multiple Myeloma

“…The antitumor activity of belantamab mafodotin was corroborated in an observational, retrospective, multicenter study in 106 adult patients with heavily pretreated RRMM. 39 Approximately half of the patients were tripleclass refractory and 11.3% were penta-class refractory. Approximately 38.0% of patients had an overall response, with a median DoR of 9 months.…”