Emerging GPRC5D-Targeted therapies for multiple myeloma: a comprehensive review.

Area of Science:

• Oncology
• Immunotherapy
• Pharmacology

Background:

• G protein-coupled receptor class C group 5 member D (GPRC5D) is a key antigen in multiple myeloma.
• Several GPRC5D-targeted therapies, including CAR T cells and antibody-drug conjugates, are in development.
• These agents represent a potential paradigm shift in multiple myeloma treatment.

Purpose of the Study:

• To review the biology of GPRC5D.
• To discuss the current and emerging applications of talquetamab in relapsed/refractory multiple myeloma.
• To examine the landscape of investigational GPRC5D-targeted drugs and their future clinical integration.

Main Methods:

• Review of current literature on GPRC5D biology and targeted therapies.
• Analysis of talquetamab's role in multiple myeloma treatment.
• Exploration of emerging GPRC5D-targeted drug development and clinical trial strategies.

Main Results:

• Talquetamab is the sole approved GPRC5D-targeted therapy, primarily for BCMA-refractory myeloma.
• Innovative strategies for GPRC5D targeting are crucial for maximizing therapeutic potential.
• Investigational trials are exploring combination immunotherapies to overcome resistance.

Conclusions:

• GPRC5D-targeted therapies offer significant efficacy but carry risks like oral, skin, nail, and cerebellar toxicity.
• Future research should prioritize optimizing dosing, identifying toxicity biomarkers, and managing adverse events.
• Balancing efficacy and toxicity is essential for the successful clinical implementation of GPRC5D-targeted treatments.