Clinical Management of Patients With Relapsed/Refractory Multiple Myeloma Treated With Talquetamab

Background Talquetamab is a bispecific antibody targeting the multiple myeloma-associated antigen G protein–coupled receptor family C group 5 member D (GPRC5D). In the phase 1/2 MonumenTAL-1 trial (NCT03399799/NCT04634552), overall responses rates were >71% in patients with triple-class exposed relapsed/refractory multiple myeloma (RRMM). Due to the distribution of the target antigen, a unique pattern of GPRC5D-associated adverse events (AEs) was observed, together with T-cell redirection–associated AEs. Management strategies for talquetamab-associated AEs are described. Discussion GPRC5D-associated AEs included dermatologic (rash, non-rash, and nail toxicities) and oral AEs (dysgeusia, dysphagia, and dry mouth). The incidence of cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) were consistent with other T-cell redirection therapies. The incidence of high-grade infections was lower than observed with B-cell maturation antigen-targeting bispecific antibodies, with less frequent use of intravenous immunoglobulin required. GPRC5D-associated AEs were mostly low grade and led to few discontinuations. Skin toxicities were managed with emollients, topical corticosteroids, and oral corticosteroids (for high-grade, persistent, or AEs that progress). Nail toxicities were commonly managed with emollients. Based on investigator experience, dose modification may be effective for controlling oral events. Observation for potential weight changes is required. Infections were managed per standard of care. CRS and ICANS were effectively managed, consistent with other trials of T-cell redirection therapies. Conclusion Although talquetamab had a distinct safety profile, AEs were considered clinically manageable and mostly low grade. With appropriate education and support, health care practitioners can ensure patients with RRMM maintain quality of life and treatment adherence. Microabstract Talquetamab had a unique pattern of T-cell– and GPRC5D–associated AEs in MonumenTAL-1. Dermatologic toxicities were managed with corticosteroids and emollients, oral AEs with dose modification, and infections per standard of care. Cytokine release syndrome/immune effector cell-associated neurotoxicity syndrome were managed consistent with other T-cell redirection therapies. GPRC5D-associated adverse events may improve or resolve over time. Overall, the safety profile was manageable with minimal discontinuations due to AEs.