Talquetamab in heavily pretreated patients with multiple myeloma, including BCMA-refractory

• Talquetamab showed similar responses and adverse event profile in this real-world cohort, including in patients ineligible for MonumenTAL-1. • Bispecific T-cell engager exposure and BDT immediately before and <6 months before talquetamab had poor outcomes. Talquetamab is a G protein–coupled receptor class C group 5 member D–targeting bispecific T-cell engager approved for patients with relapsed multiple myeloma based on the MonumenTAL-1 trial. In this retrospective study of 68 patients, we evaluated safety and efficacy of talquetamab in a real-world population across 7 US academic centers. We found that 40% of patients would have been ineligible for MonumenTAL-1 trial. Infections (29%) were far less common than in MonumenTAL-1 and with the B-cell maturation antigen (BCMA)–directed therapies (BDTs). Cytopenias and unique toxicities of talquetamab such as dysgeusia (78%) were more frequent than in MonumenTAL-1, whereas other side effects were comparable. The best overall response rate (ORR) was 71%, with 51% very good partial response or better and 25% complete response or better. At a median follow-up of 4.6 months (95% confidence interval [CI], 0.5-17.5), estimated 6-month overall survival (OS) was 74% (95% CI, 59-85). On multivariate analysis, prior bispecific antibody exposure (hazard ratio [HR], 3.87; P = .01) and extramedullary disease (HR, 2.81; P < .01) were associated with worse progression-free survival (PFS). In the BCMA-exposed group (n = 63), BDT immediately preceding talquetamab was associated with lower ORR (48% vs 81%; P ≤ .01) and shorter PFS (HR, 2.10; P = .04). Similarly, BDT within 6 months of talquetamab negatively affected ORR (57% vs 85%; P = .02), PFS (HR, 2.3; P = .03) and OS (HR, 4.8; P = .04). Overall, the safety and efficacy profile of talquetamab in this real-world data set are similar to that of the MonumenTAL-1 trial.