Susan Bal, MD, associate professor, University of Alabama at Birmingham, discusses the promising advancements in GPRC5D-directed therapies for patients with multiple myeloma, particularly those who are quad-class exposed and have exhausted multiple lines of treatment. Highlighting data from the MONUMENT series and the phase 1 trial of locabtogene autoleucel, a GPRC5D-directed chimeric antigen receptor (CAR) T-cell therapy, Dr. Bal emphasizes the high efficacy of this novel treatment, which has shown response rates exceeding 90% at the recommended phase 2 dose. Notably, these responses are durable, with a median progression-free survival of 18 months and a 12-month overall survival rate of 90%.
She explains how GPRC5D—a target distinct from BCMA—is expressed on malignant plasma cells but minimally present in healthy tissues, making it a valuable therapeutic focus. However, she also addresses on-target, off-tumor toxicities, such as taste disturbances, rash, nail changes, and rare neurologic events, which remain a key consideration in clinical development.
As the only GPRC5D-directed CAR T-cell therapy currently in advanced clinical development, locabtogene autoleucel is being evaluated in the QUINTESSENTIAL Phase 2 trial for registration approval. Dr. Bal notes its unique safety and efficacy profile compared to other CAR T therapies, including those targeting BCMA.
What sets this program apart, according to Dr. Bal, is its strong survival benefit and low incidence of high-grade infections and non-relapse mortality, even in heavily pretreated populations. These findings support the therapy’s potential not only to extend survival but also to enable patients to access additional treatment options after CAR T-cell therapy.
Dr. Bal’s commentary underscores a major step forward in addressing the unmet needs of this complex patient group.
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