Comparative Real-World Outcomes of Belantamab Mafodotin Versus Pomalidomide-Based Regimens in Relapsed/Refractory Multiple Myeloma: A Propensity-Matched Cohort Analysis
Introduction/Background/Significance: The therapeutic landscape for relapsed/refractory multiple myeloma (RRMM) continues to evolve with the introduction of novel agents such as belantamab mafodotin. However, comparative real-world data regarding the efficacy and safety profiles, especially outside of clinical trial settings, remain limited. Given belantamab's mechanism as an anti-BCMA antibody-drug conjugate and the continued reliance on pomalidomide-based regimens in advanced myeloma, it is essential to clarify how these treatments compare in everyday clinical practice.
Materials and Methods/Case Presentation/Objective: We performed a retrospective, real-world comparative outcomes analysis using the TriNetX Network. Adult patients (≥18 years) with RRMM who received either belantamab mafodotin (n=207 after matching) or a pomalidomide-based regimen (n=207 after matching) were identified. Patients with prior exposure to CAR-T, bispecific antibodies, or overlapping therapies were excluded. Propensity score matching was performed for demographics, comorbidities (including CKD, diabetes, heart failure, COPD), prior stem cell transplantation, and exposure to key myeloma agents (lenalidomide, bortezomib, cyclophosphamide, carfilzomib, thalidomide, daratumumab) to minimize confounding. Outcomes were assessed over a one-year follow-up window, starting one day after therapy initiation. Kaplan-Meier analysis was used for time-to-event outcomes, with hazard ratios (HRs) and log-rank p-values reported.
Results/Description/Main Outcome Measures: The mean age was 67 years, with similar distributions by sex and race.
Over a median follow-up of 326 days (belantamab) and 365 days (pomalidomide), all-cause mortality was significantly higher in the belantamab group (47.9% vs. 59.3% 1-year survival; HR 1.51, 95% CI 1.12–2.03, log-rank p=0.006), indicating a 51% increased risk of death compared to pomalidomide-based regimens. Hospitalization rates and emergency room visits were comparable between groups, with no significant differences observed (hospitalization HR 0.87, p=0.813; ER visits HR 0.79, p=0.62).
In terms of hematologic and immune-related toxicities, the risk of thrombocytopenia was notably higher with belantamab (HR 2.48, 95% CI 1.48–4.14, p< 0.001), corresponding to more than twice the hazard compared to pomalidomide. Neurotoxicity was numerically more common in the belantamab group but did not reach statistical significance (HR 1.66, p=0.105). Neutropenia and anemia occurred at similar rates across both cohorts (neutropenia HR 0.71, p=0.403; anemia HR 1.24, p=0.486).
Infectious complications, including septic shock (HR 0.58, p=0.177), pneumonia (HR 0.84, p=0.579), CMV infection (HR 1.16, p=0.882), candidemia (HR 1.05, p=0.975), and aspergillosis (HR 0.52, p=0.590), were infrequent and did not differ significantly between groups. Hypogammaglobulinemia (HR 1.03, p=0.927), IVIG requirement (HR 0.64, p=0.255), and rates of MDS (HR 0.88, p=0.846) or AML (HR 1.69, p=0.206) did not significantly differ. Fatigue and progression to end-stage renal disease requiring hemodialysis occurred at similar rates between the two regimens.
Conclusions: In this large, propensity-matched real-world analysis of patients with relapsed/refractory multiple myeloma, belantamab mafodotin was associated with a significantly higher risk of all-cause mortality and thrombocytopenia compared to pomalidomide-based regimens, while rates of hospitalization, infection, and other hematologic or immune toxicities were largely similar. These findings highlight the importance of close hematologic monitoring and individualized risk assessment when considering belantamab in the RRMM setting. Further studies are needed to clarify patient selection and optimize outcomes with this novel therapy.
