Talquetamab, a bispecific antibody targeting GPRC5D, demonstrated over 71% overall response rates in the MonumenTAL-1 trial for patients with triple-class exposed relapsed/refractory multiple myeloma. Due to the distribution of the GPRC5D antigen, unique adverse events (AEs) such as dermatologic (rash, nail toxicities) and oral (dysgeusia, dysphagia, dry mouth) issues were observed, alongside T-cell redirection–associated AEs like cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS). Importantly, infections were less severe compared to B-cell maturation antigen-targeting therapies, with reduced intravenous immunoglobulin use. These AEs were generally low grade, manageable, and led to few treatment discontinuations.

Management strategies for talquetamab-associated AEs included emollients and corticosteroids for dermatologic issues, dose modifications for oral symptoms, and standard care for infections. CRS and ICANS management aligned with protocols used in other T-cell redirection therapies. With appropriate education and support, healthcare providers can help patients maintain quality of life and treatment adherence, highlighting the clinical viability of talquetamab despite its distinct safety profile.

Reference: Chari A, Krishnan A, Rasche L, et al. Clinical Management of Patients With Relapsed/Refractory Multiple Myeloma Treated With Talquetamab. Clin Lymphoma Myeloma Leuk. 2024;24(10):665-693.e14. doi: 10.1016/j.clml.2024.05.003.