Yang Xu, Wang Feiqing, Yuan Xiaoshuang, Yang Bo, Chen Juan, Cheng Jinyang, Liu Guangyang, Tang Dongxin, Xu Xiao, Wang Sanbin, He Zhixu, Liu Yang, Li Yanju
Clinical Medical Research Center, The First Affiliated Hospital of Guizhou University of Traditional Chinese Medicine, Guiyang, Guizhou, China.
Academy of Medical Engineering and Translational Medicine, Tianjin University, Tianjin, China.
Front Immunol. 2024 Dec 23;15:1466443. doi: 10.3389/fimmu.2024.1466443. eCollection 2024.
Clinical studies have demonstrated the high efficacy of using chimeric antigen receptor (CAR)-T cells targeting B-cell maturation antigen (BCMA) and orphan G protein-coupled receptor, class C group 5 member D (GPRC5D) to treat relapsed or refractory multiple myeloma (RRMM). In this study, we compared the efficacy and safety of BCMA CAR-T-cell therapy (BCMA CAR-T) and GPRC5D CAR T-cell therapy (GPRC5D CAR-T) in patients with RRMM.
We retrieved and included eligible clinical trials of BCMA or GPRC5D CAR-T for RRMM patients. The primary outcomes for efficacy were overall response rate (ORR), complete response rate (CRR), minimal residual disease (MRD) negativity, and relapse rate. The primary outcomes for safety were cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS).
We incorporated 18 early-phase, single-arm clinical trials, which included 503 and 133 patients receiving BCMA CAR-T and GPRC5D CAR-T, respectively. For the GPRC5D CAR-T cohort, the estimated ORR, CRR, MRD negativity rate, and relapse rate were found to be 89.8% [95% confidence interval (CI), 82.8%-96.9%], 50.5% (95% CI, 38.0%-62.9%), 78.8% (95% CI, 53.0%-100%), and 26.0% (95% CI, 7.4%-44.6%), respectively. In the BCMA CAR-T group, the ORR was 76.3% (95% CI, 67.9%-84.7%), the CRR was 34.3% (95% CI, 25.9%-42.7%), the MRD negativity rate was 76.5% (95% CI, 63.1%-90.0%), and the recurrence rate was 57.3% (95% CI, 47.7%-66.9%). These values were significantly lower than those observed in the GPRC5D CAR-T cohort. Both BCMA and GPRC5D CAR-T demonstrated acceptable safety. The estimated incidence of BCMA CAR-T resulting in grade 3-5 CRS and ICANS was only 5.4% (95% CI, 2.0%-10.4%) and 3.3% (95% CI, 0.6%-8.0%), respectively. The estimated incidence of GPRC5D CAR-T resulting in grade 3-5 CRS and ICANS was only 1.6% (95% CI, 0.0%-6.5%) and 2.7% (95% CI, 0.7%-6.2%), respectively.
GPRC5D CAR-T potentially demonstrates enhanced effectiveness relative to BCMA CAR-T in treating patients with RRMM. Therefore, GPRC5D CAR-T can be regarded as the preferred therapeutic option for RRMM, particularly among patients who have undergone relapse subsequent to BCMA CAR-T treatment.
临床研究已证明，使用靶向B细胞成熟抗原（BCMA）和孤儿G蛋白偶联受体C类第5组成员D（GPRC5D）的嵌合抗原受体（CAR）-T细胞治疗复发或难治性多发性骨髓瘤（RRMM）具有高效性。在本研究中，我们比较了BCMA CAR-T细胞疗法（BCMA CAR-T）和GPRC5D CAR-T细胞疗法（GPRC5D CAR-T）在RRMM患者中的疗效和安全性。
我们检索并纳入了RRMM患者接受BCMA或GPRC5D CAR-T的符合条件的临床试验。疗效的主要结局指标为总缓解率（ORR）、完全缓解率（CRR）、微小残留病（MRD）阴性率和复发率。安全性的主要结局指标为细胞因子释放综合征（CRS）和免疫效应细胞相关神经毒性综合征（ICANS）。
我们纳入了18项早期单臂临床试验，其中分别有503例和133例患者接受了BCMA CAR-T和GPRC5D CAR-T治疗。对于GPRC5D CAR-T队列，估计的ORR、CRR、MRD阴性率和复发率分别为89.8%[95%置信区间（CI），82.8%-96.9%]、50.5%（95%CI，38.0%-62.9%）、78.8%（95%CI，53.0%-100%）和26.0%（95%CI，7.4%-44.6%）。在BCMA CAR-T组中，ORR为76.3%（95%CI，67.9%-84.7%），CRR为34.3%（95%CI，25.9%-42.7%），MRD阴性率为76.5%（95%CI，63.1%-90.0%），复发率为57.3%（95%CI，47.7%-66.9%）。这些数值显著低于GPRC5D CAR-T队列中的观察值。BCMA CAR-T和GPRC5D CAR-T均显示出可接受的安全性。BCMA CAR-T导致3-5级CRS和ICANS的估计发生率分别仅为5.4%（95%CI，2.0%-10.4%）和3.3%（95%CI，0.6%-8.0%）。GPRC5D CAR-T导致3-5级CRS和ICANS的估计发生率分别仅为1.6%（95%CI，0.0%-6.5%）和2.7%（95%CI，0.7%-6.2%）。
相对于BCMA CAR-T，GPRC5D CAR-T在治疗RRMM患者方面可能显示出更强的有效性。因此，GPRC5D CAR-T可被视为RRMM的首选治疗方案，尤其是在接受BCMA CAR-T治疗后复发的患者中。
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