Clinical Strategies for Managing GPRC5D-Related Adverse Events

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GPRC5D expression in hair follicles, nail beds, and specific tongue structures results in distinctive on-target, off-tumor toxicities that require proactive management strategies. Dermatologic manifestations include frequent rash responsive to topical corticosteroids, severe dry or scaly skin managed with moisturizers and exfoliants, and challenging nail toxicities ranging from brittleness to complete nail loss. Patient education regarding nail care, including keeping nails closely trimmed and using nail hardeners, helps prevent traumatic nail injuries and associated complications.

Dysgeusia represents the most challenging and impactful adverse effect, causing profound taste alterations that can significantly affect nutritional intake and quality of life. Early nutritionist involvement is crucial for developing strategies to maintain adequate caloric intake despite taste changes. While dysgeusia typically improves over 6 or moremonths with continued treatment, dose modifications and extended dosing intervals can accelerate recovery. Patients achieving rapid, deep responses may benefit from transitioning to every-4-week dosing schedules to minimize taste-related toxicities.

Additional oral complications include dry mouth (managed with biotin supplementation) and dysphagia requiring swallowing assessments and dietary modifications. Unlike B-cell maturation antigen-directed therapies, GPRC5D-targeted agents cause less profound hypogammaglobulinemia, making intravenous immunoglobulin prophylaxis an individualized decision rather than a universal requirement. Standard cytokine release syndrome and neurotoxicity management protocols apply, with pneumocystis jirovecii pneumonia prophylaxis recommended for all patients receiving GPRC5D-directed bispecific therapy.