Perspectives on Talquetamab and its Utility in the Treatment of Multiple Myeloma: Safety, Efficacy and Place in Therapy

Kevin C Miller,1 Issam Hamadeh,2 Carlyn Rose Tan1 1Myeloma Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA; 2Department of Pharmacy, Memorial Sloan Kettering Cancer Center, New York, NY, USACorrespondence: Carlyn Rose Tan, Myeloma Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, 530 E 74th Street, New York, NY, 10021, USA, Tel +1646-608-3778, Email [email protected]: Despite recent advancements, most patients with multiple myeloma eventually develop resistance to available treatments, highlighting the need for new therapeutic strategies. G protein-coupled receptor class C group 5 member D (GPRC5D) has emerged as a viable novel therapeutic target on myeloma cells, leading to the clinical development of talquetamab, the first GPRC5D-directed bispecific T-cell engager (TCE). Talquetamab was granted accelerated approval in August 2023 by the Food and Drug Administration. Besides expected short-term toxicities including cytokine release syndrome, neurotoxicity and cytopenias, talquetamab commonly causes adverse events involving the oral cavity, nails, and skin, which can negatively impact quality of life and in some cases lead to treatment discontinuation. Despite these pitfalls, talquetamab yields responses in most treated patients, which in a subset are durable. There are now several clinical trials investigating talquetamab in different clinical contexts in multiple myeloma, as well as in combination with other anti-myeloma agents. Beyond results from these prospective trials, better biologic understanding of resistance mechanisms to talquetamab and improved strategies to mitigate common toxicities are key questions as talquetamab finds its place in the treatment of multiple myeloma.Keywords: multiple myeloma, talquetamab, GPRC5D, toxicity management