Targeting GPRC5D With CAR-T Cells in Relapse/Refractory Multiple Myeloma: Case Report and Literature Review.

Multiple myeloma (MM) is the second most common hematologic malignancy, and patients with relapsed/refractory MM (RRMM) face limited treatment options and a poor prognosis. Recently, CAR-T cell therapy targeting G-protein-coupled receptor, class C group 5 member D (GPRC5D) has shown promising efficacy and safety in preclinical studies, offering new hope for patients with RRMM. We report the successful treatment of a 48-year-old female patient with relapsed/refractory nonsecretory MM. The patient had high-risk factors, including 1q21 amplification and TP53 deletion, and had relapsed after seven lines of therapy, including autologous hematopoietic stem cell transplantation, proteasome inhibitors, immunomodulatory agents, PD-1 inhibitors, and CD38 monoclonal antibodies. She also developed extramedullary disease. Eventually, she received CAR-T cell therapy targeting GPRC5D, which led to the complete disappearance of extramedullary lesions and a sustained complete remission lasting up to 17 months. In conclusion, CAR-T cell therapy targeting GPRC5D is highly effective and well-tolerated in patients with RRMM, especially those with high-risk factors. Further studies with larger cohorts and longer follow-up periods are needed to validate the clinical application of GPRC5D-targeted CAR-T cell therapy in RRMM, particularly for patients who have failed BCMA-targeted therapies.