Real-world vs. clinical trial data of belantamab mafodotin's ocular toxicities: A comparative analysis

Abstract Introduction: Belantamab mafodotin is an antibody-drug conjugate (ADC) that is used for treatment of relapsed/refractory Multiple Myeloma (RRMM). While it has demonstrated potential for Myeloma patients, this ADC presents with serious ocular toxicities, such as keratopathy and blurred vision (Nooka et al., 2023), which can impact patients' quality of life and overall adherence to Belantamab mafodotin. Objective: This study examines the incidence of ocular toxicities in real-world RRMM patients who are using Belantamab mafodotin, compared to rates reported in a key clinical trial. Methods: Trinetx, a real-world data platform, was used to assess outcomes in RRMM patients treated with Belantamab mafodotin. Using information from Trinetx's US Collaborative Network, which includes up to 72 health care organizations, we evaluated patients' demographics (age, race, sex), treatment-related adverse events, and patients' mean follow-up duration. Patients experiencing the outcome of interest prior to treatment were excluded from each outcome analysis. Findings from Trinetx were then compared to published literature from the DREAMM-2 clinical trial, which led to Belantamab mafodotin's FDA approval in 2020 (U.S. Food and Drug Administration, 2024). Results: On Trinetx, the initial cohort yielded 345 patients with RRMM treated with Belantamb mafodotin. The mean follow-up duration for these real-world patients was 615.6 days. Trinetx data also showed a mean age of 72 years old, with a patient population that was 50.1% male patients, 47.5% female, 2.9% of unknown sex, 69.9% White, and 15.4% Black. In comparison to the DREAMM-2 clinical trial, the initial cohort of patients had a median age of 65 years old, with a patient population that was 52.6% male, 47.4% female, 74.2% White, and 16.5% Black (Lonial et al., 2020). In the real-world Trinetx data, 71/330 (21.5%) of patients experienced the keratopathy outcome and 33/307 (10.7%) of patients experienced the blurred vision outcome. In relation, in the DREAMM-2 study, keratopathy was the most common ocular toxicity with 67/95 (70.5%) of patients complaining of this adverse effect. In addition, 22.1% (17/95) of patients reported blurred vision in the clinical trial (Lonial et al., 2020). When comparing real-world patients to clinical trial patients, we observed an odds ratio of 0.11 (CI: 0.07 to 0.19) for keratopathy and an odds ratio of 0.55 (CI: 0.29 to 1.04) for blurred vision. Conclusions: When comparing the Trinetx data to the DREAMM-2 clinical trial, there is a significant difference in the reported risk of keratopathy for patients. Upon consideration, we hypothesize this discrepancy could be caused by a lack of regular follow-up in the real world and underreporting by real-world patients. We also believe that there is better monitoring of ocular toxicities in a clinical trial, which would lead to prompt drug therapy interruption and swift dose adjustment. Due to the ocular toxicities that are present in both real-world patients and clinical trial patients, this medication should continue to be clinically evaluated to ensure safety in RRMM patients.