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.