Talquetamab in Multiple Myeloma: Efficacy, Safety, and Future Directions

Abstract

Relapsed and refractory multiple myeloma (RRMM) remains a challenging condition despite advances in immunotherapies. Novel bispecific antibodies (BsAbs), including talquetamab, have shown promising efficacy in heavily pretreated patients, even those with triple- and penta-refractory disease. Talquetamab, recently approved by the FDA and EMA, is indicated for patients who have progressed after at least three or four prior lines of therapy (LOTs). Administered following a step-up dosing phase to manage cytokine release syndrome (CRS), talquetamab demonstrated a high overall response rate (ORR) of approximately 70%, including in patients previously treated with T-cell redirecting therapies. Its safety profile is consistent with other BsAbs, with hematologic adverse events such as anemia and neutropenia commonly reported, alongside unique on-target off-tumor toxicities like dysgeusia and skin-related events. Infections were less frequent compared to other BsAbs. The optimal sequencing of talquetamab and other therapies, including CAR-T cell treatments, remains an area of active research, as resistance to anti-BCMA therapies presents ongoing clinical challenges. Current trials are exploring the use of talquetamab in combination therapies, as well as therapeutic strategies post-treating progression. The real-world data further support talquetamab's efficacy, making it a valuable addition to the RRMM treatment landscape.

Keywords: BsAbs; MM; talquetamab; therapy.

FIGURE 1

Talquetamab, an off‐the‐shelf, full‐sized, humanized BsAb redirects to MM cells by simultaneously binding CD3 on T‐cells and GPRC5D on plasma cells, thereby forming a highly efficient immune synapse between T‐cells and MM cells, which enhances T‐cell‐mediated cytotoxicity. Upon activation, T‐cells release granules containing granzymes and perforins, leading to malignant cell death.