Belantamab Mafodotin in Patients with Relapsed/Refractory Multiple Myeloma: Results of the Compassionate Use or the Expanded Access Program in Spain

Abstract

Belantamab-mafodotin (belamaf) is a novel antibody-drug conjugate targeting B-cell maturation antigen that showed anti-myeloma activity in patients with relapsed and refractory multiple myeloma (RRMM). We performed an observational, retrospective, and multicenter study aimed to assess the efficacy and safety of single-agent belamaf in 156 Spanish patients with RRMM. The median number of prior therapy lines was 5 (range, 1–10), and 88% of patients were triple-class refractory. Median follow-up was 10.9 months (range, 1–28.6). The overall response rate was 41.8% (≥CR 13.5%, VGPR 9%, PR 17.3%, MR 2%). The median progression-free survival was 3.61 months (95% CI, 2.1–5.1) and 14.47 months (95% CI, 7.91–21.04) in patients achieving at least MR (p < 0.001). Median overall survival in the entire cohort and in patients with MR or better was 11.05 months (95% CI, 8.7–13.3) and 23.35 (NA-NA) months, respectively (p < 0.001). Corneal events (87.9%; grade ≥ 3, 33.7%) were the most commonly adverse events, while thrombocytopenia and infections occurred in 15.4% and 15% of patients, respectively. Two (1.3%) patients discontinued treatment permanently due to ocular toxicity. Belamaf showed a noticeably anti-myeloma activity in this real-life series of patients, particularly among those achieving MR or better. The safety profile was manageable and consistent with prior studies.

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].…”

Treatment with low‐dose, single‐agent belantamab mafodotin is safe and provides long‐term responses in heavily pretreated multiple myeloma patients

“…13 According to our analysis, most patients responded and improved their responses over the first few months of therapy, reaching VGPR/ CR. These results, which are superior to those reported in most prospective and retrospective real-world studies, 1,4,5,7,8,14,15 might reflect the decreased ocular toxicity achieved with our low-dose belantamab strategy, enabling continues treatment and deepening of response. These deep responses were translated into prolonged PFS.…”

“…In the largest real-world series published to date, including 156 patients, ORR was 41.8% (4), translated into median progressionfree survival (PFS) and overall survival (OS) of 3.6 and 11.5 months, respectively. 4 Corneal event was common (87.9%; Grade ≥3, 33.7%) but their effect on treatment schedule was not reported. 4 In another real-world series of 106 patients, 5 ORR (45.5%), PFS, and OS (4.7 and 14.5 months, respectively) were similar, and most (55%) patients experienced dose delays.…”

“…4 Corneal event was common (87.9%; Grade ≥3, 33.7%) but their effect on treatment schedule was not reported. 4 In another real-world series of 106 patients, 5 ORR (45.5%), PFS, and OS (4.7 and 14.5 months, respectively) were similar, and most (55%) patients experienced dose delays. Ocular toxicity was the main reason for treatment delays (71%).…”

Michael Acceptors as Anti-Cancer Compounds: Coincidence or Causality?

“…These include auristatins F, M and W, as well as monomethyl auristatin F (MMAF), PF-06380101, Duostatin 5 and keto-auristatin PE (KAPE). For example, MMAF was used in Belantamab mafodotin ADC for the treatment of relapsed or refractory myeloma [ 342 ]. Another Mafodotin-based ADC, Depatuxizumab mafodotin, targets EGFR in glioblastoma and EGFR-overexpressed tumors [ 343 ].…”