GPRC5D-targeted therapy is gaining traction as a promising strategy in treating multiple myeloma, offering a range of options for patients, particularly those who have not yet undergone or are being bridged to B-cell maturation antigen (BCMA) therapies. This approach, highlighted in a recent Training Academy, underscores the importance of GPRC5D due to its higher expression in malignant plasma cells compared to normal cells.
Clinical Efficacy and Trial Data
Talquetamab-tgvs (Talvey), the most common and only approved GPRC5D-targeted therapy, has been evaluated in the phase 1/2 MonumenTAL-1 trial (NCT03399799; NCT04634552) and the phase 1/2 MonumenTAL-3 trial (NCT05455320). These trials suggest that combination therapies involving talquetamab may yield higher efficacy rates than monotherapy approaches. The exploration of GPRC5D as a target is driven by the need for diverse treatment options in multiple myeloma, especially for patients who may benefit from therapies used prior to BCMA-targeted interventions or as a bridge to CAR-T cell therapy.
Safety Profile and Toxicity Management
One of the notable advantages of GPRC5D-targeted therapies like talquetamab is their manageable toxicity profile. The most common adverse events include oral and skin-related issues, which are generally less severe compared to those associated with bispecific antibodies. Dose de-escalation strategies and monthly treatment regimens have proven effective in mitigating these toxicities, particularly dysgeusia. Importantly, talquetamab has not been associated with adverse effects related to cardiac, pulmonary, renal, or neuropathy-related complications. Furthermore, GPRC5D-targeted therapies exhibit a lower risk of infectious toxicity, reducing the need for intravenous immunoglobulin supplementation.
Clinical Implications
The emergence of GPRC5D as a therapeutic target represents a significant advancement in the treatment of multiple myeloma. Its unique expression pattern and manageable safety profile make it an attractive option for patients at various stages of the disease. As research continues, combination therapies and optimized dosing strategies are expected to further enhance the efficacy and tolerability of GPRC5D-targeted treatments, offering new hope for improved outcomes in multiple myeloma patients.
