Talquetamab in Heavily Pretreated Multiple Myeloma Patients, 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, BCMA-directed therapy (BDT) immediately before and BDT <6 months before talquetamab had poor outcomes

Talquetamab is a G protein-coupled receptor class C group 5 member D (GPRC5D) targeting bispecific T-cell engager (TCE) 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 seven 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 BCMA-directed therapies (BDT). Cytopenias and unique toxicities of talquetamab such as dysgeusia (78%) were more frequent than in MonumenTAL-1, while other side effects were comparable. The best overall response rate (ORR) was 71%, with 51% ≥ very good partial response and 25% ≥ complete response. At a median follow-up of 4.6 months (95% CI, 0.5–17.5), estimated 6-month OS was 74% (95% CI 59-85). On multivariate analysis, prior bispecific antibody exposure (HR 3.87, p=0.01) and extramedullary disease (HR 2.81, p<0.01) 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=<0.01) and shorter PFS (HR 2.10, p=0.04). Similarly, BDT within 6 months of talquetamab negatively affected ORR (57% vs 85%, p=0.02), PFS (HR 2.3, p=0.03) and OS (HR 4.8, p=0.04). Overall, the safety and efficacy profile of talquetamab in this real-world dataset are similar to the MonumenTAL-1 trial.