Oncology Advances: Adverse Event Management Strategies for Patients With MM Receiving Talquetamab Advances

G protein-coupled receptor family C group 5 member D (GPRC5D) is an orphan receptor expressed in malignant plasma cells. The bispecific antibody, talquetamab, targets GPRC5D to redirect T cells to facilitate GPRC5D-expressing myeloma cell death. Talquetamab is the only GPRC5D-targeting bispecific antibody approved in the United States for the treatment of multiple myeloma (MM).

In relapsed/refractory MM, talquetamab demonstrated overall response rates >71% with weekly and every other week dosing in the open-label, single-arm, phase 1/2 MonumenTAL-1 study. Common adverse events (AEs) associated with talquetamab include cytokine release syndrome (CRS), skin-related AEs, nail-related AEs, and dysgeusia. Immune effector cell-associated neurotoxicity syndrome (ICANS) and infections were also reported. Strategies for monitoring and managing AEs are important to consider when administering talquetamab. 

A recent study by Donna Catamero, Mount Sinai School of Medicine, New York, New York, et al, provides guidance on practical management of patients with relapsed/refractory MM receiving talquetamab, based on experience from the MonumenTAL-1 trial. This study used step-up dosing to mitigate risk of high-grade CRS and ICANS.

For CRS/ICANS, researchers noted that close monitoring during step-up dosing in the first full dose of talquetamab is recommended and should be managed per guidelines for other bispecific antibodies. For infections, researchers noted that most grade 3/4 infections occurred during the first 100 days of treatment. The incidence of grade 3/4 infections associated with talquetamab were lower than that seen with B-cell maturation antigen (BCMA)-directed bispecific antibodies. Infections can be prevented using strategies similar to that of other non-BCMA-directed therapies for MM.

For skin, nail, and oral AEs, researchers note that dermatologists, dentists, and nutritionists can be consulted to provide additional guidance on properly managing these AEs and confirming that they are treatment-associated. Oral AEs can be managed with nutritional support and dose modifications in some patients. Oral AEs led to few treatment discontinuations and may partially or fully resolve in some patients. Skin-related AEs can be managed with emollients and topical corticosteroids, with oral corticosteroids used for more severe cases. However, researchers explain that most skin-related AEs are benign and treatable.

Sources:

1. Chari A, Minnema MC, Berdeja JG, et al. Talquetamab, a T-Cell-Redirecting GPRC5D Bispecific Antibody for Multiple Myeloma. N Engl J Med. 2022 Dec 15;387(24):2232-2244. doi:10.1056/NEJMoa2204591.
2. Catamero D, Purcell K, Ray C, et al. Practical Management of Patients With Relapsed/Refractory Multiple Myeloma Receiving Talquetamab, a GPRC5D.CD3 Bispecific Antibody: Experience in MonumenTAL-1. Presented at International Myeloma Society Annual Meeting; September 27-30, 2023; Athens, Greece. NSP-03.