Incidence of ocular toxicities in patients with relapsed/refractory multiple myeloma treated with belantamab mafodotin: A systematic review and meta-analysis of phase 3 randomized controlled trials.

Abstract

12040 Background: Belantamab mafodotin is a novel antibody-drug conjugate approved by the FDA in August 2020 to treat relapsed/refractory multiple myeloma (RRMM). However, it was withdrawn from the market in March 2023 following the DREAMM-3 randomized controlled trial (RCT) failure to show superior progression-free survival (PFS). Later in 2024, further RCTs published (DREAMM-7 & 8) have shown PFS benefit which opens the door to a possible FDA reapproval in the future. Several concerns about ocular adverse events (AEs) have emerged from those trials. This meta-analysis aims to evaluate the incidence of those events in patients with RRMM receiving belantamab. Methods: A systematic literature search was performed across MEDLINE and EMBASE databases up to December 31, 2024. Phase 3 RCTs investigating belantamab regimens in RRMM were included. Pooled risk ratios (RR) with 95% confidence intervals (CI) were calculated using the Mantel-Haenszel method. Heterogeneity was assessed using Cochran’s Q-statistic. Fixed effects model was employed. Results: A total of 1,102 patients from three phase 3 RCTs (DREAMM-3, DREAMM-7, DREAMM-8) were analyzed. The following ocular AEs were noted more frequently in the belantamab group compared to the control group: any-grade (AG) ocular AEs 76.85% vs 24.95% (RR 3.30; 95% CI: 2.80–3.89; P < 0.00001), high-grade (HG) ocular AEs 34.65% vs 2.03% (RR 17.61; 95% CI: 9.40–33.00; P < 0.00001), AG dry eyes (DE) 45.16% vs 6.69% (RR 7.47; 95% CI: 5.29–10.54; P < 0.00001), HG DE 6.24% vs 0% (RR 21.40; 95% CI: 4.40–104.07; P = 0.0001), AG blurred vision (BV) 59.77% vs 10.14% (RR 6.54; 95% CI: 4.97–8.60; P < 0.00001), HG BV 14.78% vs 0.41% (RR 27.39; 95% CI: 8.86–84.68; P < 0.00001), AG photophobia 36.95% vs 2.64% (RR 15.55; 95% CI: 8.97–26.96; P < 0.00001), HG photophobia 1.81% vs 0% (RR 7.08; 95% CI: 1.40–35.70; P = 0.02), AG eye irritation (EI) 37.27% vs 5.48% (RR 7.60; 95% CI: 5.17–11.19; P < 0.00001), HG EI 3.28% vs 0% (RR 12.23; 95% CI: 2.52–59.33; P = 0.002), AG eye pain (EP) 26.27% vs 3.04% (RR 9.40; 95% CI: 5.61–15.76; P < 0.00001), AG foreign body eye sensation (FBES) 41.71% vs 4.26% (RR 10.68; 95% CI: 6.94–16.45; P < 0.00001), AG cataract 16.58% vs 9.13% (RR 2.06; 95% CI: 1.49–2.85; P < 0.0001), and HG cataract 4.76% vs 2.64% (RR 2.08; 95% CI: 1.10–3.94; P = 0.02). No statistically significant difference was noted between the two treatment arms in terms of HG EP or FBES. Conclusions: This study revealed a significantly increased risk of ocular AEs in patients with RRMM treated with belantamab compared to the other traditional myeloma treatments. Close monitoring and early intervention are crucial for prompt identification and providing the appropriate management for those events in order to optimize the patients’ quality of life and compliance.