肿瘤细胞治疗研究
英文原题：The fully human anti-GPRC5D CAR T-cell therapy RD118 induces durable remissions in relapsed/refractory multiple myeloma.
The fully human anti-GPRC5D CAR T-cell therapy RD118 induces durable remissions in relapsed/refractory multiple myeloma.
这些结果支持 RD118 是重度经治 R/R MM 患者一种高效且安全的治疗选择。
GPRC5D已成为复发/难治性多发性骨髓瘤（R/R MM）一种有前景的治疗靶点，尤其适用于既往接受靶向B细胞成熟抗原（BCMA）的嵌合抗原受体（CAR）T细胞治疗后疾病进展的患者。RD118是一种新型CAR-T疗法，采用全人源单域抗体片段靶向GPRC5D。在这项I期研究中，18例复发/难治性患者（17例MM患者及1例既往患原发性浆细胞白血病者）接受单次RD118输注，剂量为每千克体重1.0×10^6、2.0×10^6或3.0×10^6个CAR阳性T细胞。中位随访17.0个月时，总缓解率（ORR）为94.4%，其中72.2%达到完全缓解或严格完全缓解。在7例既往接受过BCMA靶向CAR-T治疗的患者中，ORR为85.7%。无进展生存期（PFS）中位数为18.2个月（95%置信区间14.4个月至无法估算），12个月PFS率和总生存率分别为82.1%和93.3%。88.9%的患者发生细胞因子释放综合征，主要为1至2级。1例患者发生3级免疫效应细胞相关神经毒性，并在72小时内缓解。未报告小脑毒性或治疗相关死亡。这些结果支持RD118是既往接受多线治疗的R/R MM患者一种高效且安全的治疗选择。本试验在ClinicalTrials.gov注册，编号为NCT05759793和NCT05219721。
GPRC5D has emerged as a promising therapeutic target in relapsed/refractory multiple myeloma (R/R MM), particularly following progression after B-cell maturation antigen (BCMA)-directed chimeric antigen receptor (CAR) T-cell (CAR-T) therapies. RD118 is a novel CAR-T therapy incorporating a fully human single-domain antibody fragment targeting GPRC5D. In this phase 1 study, 18 R/R patients (17 with MM and 1 with a history of primary plasma cell leukemia) received a single infusion of RD118 at 1.0 106, 2.0 106, or 3.0 106 CAR+ T cells per kg. At a median follow-up of 17.0 months, the overall response rate (ORR) was 94.4%, including 72.2% complete or stringent complete responses. Among the 7 patients previously exposed to BCMA-directed CAR-T therapy, ORR reached 85.7%. Median progression-free survival (PFS) was 18.2 months (95% confidence interval, 14.4 to not estimable), with 12-month PFS and overall survival rates of 82.1% and 93.3%, respectively. Cytokine release syndrome occurred in 88.9% of the patients, primarily grade 1 to 2. One patient developed grade 3 immune effector cell-associated neurotoxicity, which resolved within 72 hours. No cerebellar toxicities or treatment-related deaths were reported. These findings support that RD118 is a highly effective and safe therapeutic option for heavily pretreated R/R MM. This trial was registered at www.clinicaltrials.gov as #NCT05759793 and #NCT05219721.
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