Safety Updates and Concluding Thoughts From Extended Follow-Up of MonumenTAL-1
Panelists discuss how talquetamab shows a more favorable safety profile with significantly lower high-grade infection rates compared with B-cell maturation antigen (BCMA)–directed bispecifics, although a new cerebellar toxicity signal requires monitoring.
EP: 1.Later R/R MM Treatment Landscape and Unmet Needs
EP: 2.ASCO 2025: MonumenTAL-1 Extended Follow-Up for Talquetamab in R/R MM
EP: 3.Insights From MonumenTAL-1: Impressions of Updated Efficacy Outcomes
EP: 4.MonumenTAL-1: Implications of Talquetamab, Prior TCR, and Sequencing for R/R MM
EP: 5.Safety Updates and Concluding Thoughts From Extended Follow-Up of MonumenTAL-1
EP: 6.Talquetamab in R/R MM: Managing GPRC5D-direced AEs, Prophylaxis, and New Safety Signals
The safety profile of talquetamab demonstrates significant advantages over BCMA-directed bispecific antibodies, particularly regarding infection risk management. Although cytokine release syndrome remains common with T-cell redirecting therapies, talquetamab’s unique targeting of GPRC5D results in substantially lower rates of severe infections compared with BCMA-directed alternatives. Infection rates with talquetamab were 61% to 71% overall, with grade 3/4 infections occurring in 20% to 25% of patients, compared with over 50% grade 3/4 infection rates seen with BCMA-directed bispecifics.
The mechanistic basis for reduced infection risk lies in GPRC5D’s expression pattern, which primarily targets myeloma cells and other plasma cells while sparing healthy B-lymphocytes. This selective targeting preserves immune function more effectively than BCMA-directed therapies, which affect earlier B-cell populations and require more intensive immunoglobulin replacement therapy. Clinical experience shows that immunoglobulin levels typically recover within several months of talquetamab initiation, often allowing discontinuation of supplemental intravenous immunoglobulin therapy.
A novel safety signal identified with talquetamab involves ataxia or cerebellar toxicity, though this occurs in less than 1% of patients. Although the incidence is low, the potentially debilitating nature of this adverse effect requires patient education and clinical monitoring. Health care providers are implementing strategies including patient counseling about balance problems, routine cerebellar function testing during clinic visits, and early intervention protocols. The overall safety profile remains favorable with no treatment-related deaths and very low discontinuation rates due to adverse events, making talquetamab a viable option for many patients, including those with significant comorbidities.
