In a Chinese single-center phase II trial reported in the Journal of Clinical Oncology, Xia et al found that anti–G protein–coupled receptor, class C group 5 member D (GPRC5D) chimeric antigen receptor (CAR) T cells showed activity in patients with relapsed or refractory multiple myeloma.
In the study, 33 patients enrolled between September 2021 and March 2022 at the Affiliated Hospital of Xuzhou Medical University received infusions of 2 x 106/kg anti-GPRC5D CAR T cells after lymphodepletion. The primary endpoint was the proportion of patients who achieved partial response or better.
Median follow-up was 5.2 months (range = 3.2–8.9 months). Response was achieved in 30 of 33 patients (91%, 95% confidence interval [CI] = 76%–98%), including a stringent complete response in 11 (33%), a complete response in 10 (30%), a very good partial response in 4 (12%), and a partial response in 5 (15%). Median time to first responses was 0.5 month (range = 0.5–3.0 months), and median time to best response was 1.8 months (range = 0.5–6.0 months).
At the time of analysis, disease progression was observed in 3 patients with response, including 1 of 21 with a stringent complete response or a complete response. Partial response or better was observed in all nine patients who had received prior anti–B-cell maturation antigen (BCMA) CAR T-cell therapy, including a complete response in four. These patients included two with repeated anti-BCMA CAR T-cell infusions with no response to the last infusion.
Grade ≥ 3 hematologic toxicities included neutropenia in 100% of patients, anemia in 52%, and thrombocytopenia in 45%. Cytokine-release syndrome occurred in 25 patients (76%), all grade 1 or 2. Neurotoxicity occurred in three patients (9%), consisting of grades 2 and 3 immune effector cell–associated neurotoxicity syndrome in two and grade 3 headache in one.
The investigators concluded: “Anti-GPRC5D CAR T-cell therapy showed an encouraging clinical efficacy and manageable safety profile in patients with [relapsed or refractory multiple myeloma]. For patients with [multiple myeloma] that progressed after anti-BCMA CAR T-cell therapy or that is refractory to anti-BCMA CAR T-cell therapy, anti-GPRC5D CAR T-cell therapy might be a potential alternative option.”
Kailin Xu, MD, of the Department of Hematology, Affiliated Hospital of Xuzhou Medical University, Xuzhou, is the corresponding author of the Journal of Clinical Oncology article.
Disclosure: The study was supported by the National Natural Science Foundation of China. For full disclosures of the study authors, visit ascopubs.org.
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