Talquetamab in patients with relapsed/refractory multiple myeloma: 3-year follow-up of the phase 1/2 MonumenTAL-1 study.

Talquetamab is the first and only approved bispecific antibody targeting G protein-coupled receptor class C group 5 member D (GPRC5D) for treatment of relapsed/refractory multiple myeloma based on results from the phase 1/2 MonumenTAL-1 study. Here, we report efficacy and ongoing safety from MonumenTAL-1 with 3 years of follow-up. Patients naïve to T-cell redirection therapy (TCR) received talquetamab 0.4 mg/kg weekly (n=143) or 0.8 mg/kg every other week (n=154); a separate cohort received prior TCR (n=78, either talquetamab dose). Median follow-up was 38, 31, and 30 months in the 3 cohorts, respectively, as of September 2024. Overall response rate was 67-74% and complete response or better rate was 33-42%. Median progression-free survival was 7.5, 11.2, and 7.7 months, and median overall survival (OS) was 34.0 months, not reached, and 28.3 months (36-month OS rates 49.3%, 60.8%, and 44.6%), in the 3 cohorts, respectively. The most common adverse events (AEs) were cytokine release syndrome (73-79%; grade 3/4, 0.6-2.1%), taste changes (72-76%), and infections (61-78%; grade 3/4, 21-26%). Ataxia/balance disorders occurred in 5.3% of patients (no grade 4/5 events). Dose reduction and discontinuation rates due to AEs remained low; no patients died due to talquetamab-related AEs. With 3 years of follow-up, talquetamab continued to demonstrate high rates of deep and durable responses. The long-term safety profile was comparable to previous results and continued to show lower risk of high-grade infections relative to approved BCMA-targeting bispecific antibodies. NCT03399799 (phase 1) and NCT04634552 (phase 2).