摘要
G蛋白偶联受体,C类5组成员D(G-protein-coupled receptor family C group 5 member D,GPRC5D)被认为是多发性骨髓瘤(multiple myeloma,MM)免疫治疗的潜在靶标。2021年9月1日—2022年3月23日,本Ⅱ期单臂临床试验共纳入33例复发/难治(relapsed or refractory,R/R)MM患者(18~70岁),在接受淋巴细胞清除化疗后输注2×106/kg抗GPRC5D嵌合抗原受体(chimeric antigen receptor,CAR)-T细胞,随后进行有效性和安全性的评估。在中位随访5.2(3.2~8.9)个月时,患者总体反应率为91%(95%CI 76%~98%,30/33例),包括11例(33%)严格意义上的完全缓解,10例(30%)完全缓解,4例(12%)非常好的部分缓解和5例(15%)部分缓解。9例既往接受过抗B细胞成熟抗原(B-cell maturation antigen,BCMA)CAR-T细胞治疗的患者疗效均达部分缓解或以上,其中包括2例接受过2次或以上抗BCMA CAR-T细胞输注的患者。3级或更高的血液学毒性为中性粒细胞减少[33例(100%)]、贫血[17例(52%)]和血小板减少症[15例(45%)]。33例患者中25例(76%)发生细胞因子释放综合征(均为1级或2级),3例患者发生神经毒性(1例2级和1例3级免疫效应细胞相关神经毒性综合征,1例3级头痛)。综上所述,抗GPRC5D CAR-T细胞疗法在R/R MM患者中表现出令人鼓舞的临床疗效和可控的安全性。对于抗BCMA CAR-T细胞治疗后进展或无效的MM患者,抗GPRC5D CAR-T细胞治疗可能是一种潜在的替代选择。
G protein-coupled receptor,class C group 5 member D(GPRC5D)is considered to be a promising surface target for multiple myeloma(MM)immunotherapy.From Sep 1,2021,to Mar 23,2022,33 patients(18-70 years)with relapsed or refractory(R/R)MM were enrolled in this phaseⅡsingle-arm clinical trial.Lymphodepletion was performed before patients received 2×10~6/kg anti-GPRC5D chimeric antigen receptor(CAR)-T cells.Efficacy was evaluated in eligible patients.At a median follow-up of 5.2(3.2-8.9)months,the overall response rate was 91%(95%CI 76%-98%,30 of 33 patients),including 11 cases(33%)with stringent complete responses,10 cases(30%)with complete responses,4 cases(12%)with very good partial responses,and 5 cases(15%)with partial responses(PR).PR or better were observed in 9 cases(100%)with previous anti-B-cell maturation antigen(BCMA)CAR-T cell therapy,including 2 patients who had received repeated anti-BCMA CAR-T cell infusions with no responses at the last time.Grade 3 or higher hematological toxicities were neutropenia(33 cases[100%]),anemia(17 cases[52%]),and thrombocytopenia(15 cases[45%]).Cytokine release syndrome occurred in 25(76%)of 33 patients(all were grade 1 or 2),and neurotoxicities occurred in 3 patients(one grade 2 and one grade 3 ICANS,one grade 3 headache).In conclusion,anti-GPRC5D CAR-T cell therapy showed an encouraging clinical efficacy and manageable safety profile in patients with R/R MM.For patients with MM progressed after anti-BCMA CAR-T cell therapy or refractory to anti-BCMA CAR-T cell,anti-GPRC5D CAR-T cell therapy might be a potential alternative option.
作者
夏洁云
徐开林
XIA Jieyun;XU Kailin(Department of Hematology,the Affiliated Hospital of Xuzhou Medical University,Xuzhou,221002,China;Blood Diseases Institute,Xuzhou Medical University;Jiangsu Key Laboratory of Bone Marrow Stem Cells)
出处
《临床血液学杂志》
2023年第7期477-481,共5页
Journal of Clinical Hematology
基金
国家自然科学基金重点项目(No:81930005)
国家自然科学基金面上项目(No:82270232)。
