Real-World Evaluation of Talquetamab for the Treatment of Relapsed/Refractory Multiple Myeloma (RRMM): An International Myeloma Working Group Immunotherapy Registry Real-World Analysis

Talquetamab is a GPRC5D × CD3 bispecific antibody approved for relapsed/refractory multiple myeloma (RRMM). This is the first real-world study to comprehensively report muco-cutaneous toxicities, infections, and efficacy of talquetamab in 151 patients across five countries with the longest follow-up reported enabling better efficacy and toxicity estimates. The median age was 64 years; high-risk cytogenetics were present in 42%; ECOG ≥ 2 in 22%; 12% had creatinine clearance < 30; and 55% would not have met MonumenTAL-1 eligibility. Patients received a median of 6 prior lines of therapy, 53% were penta-refractory, and 75% received prior BCMA therapy. Talquetamab was associated with skin toxicity in 39.7%, nail toxicity in 75.5%, dysgeusia in 60.4%, and oral toxicities in 62.9%, with grade ≥ 3 events uncommon (≤ 4%) and dose interruptions infrequent (9.6% for skin toxicity, 6.9% for dysgeusia, and 4.0% for oral toxicities). These findings underscore the need for improved supportive care for muco-cutaneous toxicities. In multivariate analysis, only platelet count < 50 (HR 1.8, 95% CI 1.15–2.83) was associated with inferior PFS, while penta-refractory status, absolute lymphocyte count < 0.4, and prior BCMA-targeted therapy were not statistically significant. With a median follow-up of 12.7 months, the overall response rate was 67.6%, median progression-free survival was 7 months, and 12-month overall survival was 65%. This study shows that talquetamab efficacy is maintained in a heavily pretreated real-world population with high prior BCMA exposure and notable comorbidity burden.