嵌合抗原受体 T 细胞与双特异性抗体作为多发性骨髓瘤三线或后线治疗的比较：一项荟萃分析。
Comparison of CAR T-cell and bispecific antibody as third-line or later-line treatments for multiple myeloma: a meta-analysis.
机构信息
Department of Hematology, Beijing Tongren Hospital, Capital Medical University, Beijing, China.
Capital Medical University, Beijing, China.
出版信息
J Immunother Cancer. 2024 Nov 17;12(11):e010064. doi: 10.1136/jitc-2024-010064.
BACKGROUND
CAR-T-cell therapy and bispecific antibody have revolutionized the treatment landscape for multiple myeloma. However, there is currently a lack of studies comparing the efficacy and safety of these two approaches. This meta-analysis assesses the efficacy and safety of B-cell maturation antigen (BCMA)-directed CAR-T-cell therapies and BCMA×CD3 bispecific antibodies as third-line or later interventions for relapsed/refractory multiple myeloma (RRMM).
METHODS
We searched PubMed, Embase, Web of Science, and Cochrane databases up to May 31, 2024, identifying 11 eligible studies encompassing 1269 participants. Random-effects models evaluated the primary (complete response (CR) rate) and secondary (overall response rate (ORR)) outcomes, while meta-regression analyses adjusted for relevant covariates.
RESULTS
CAR-T-cell therapy achieved significantly higher pooled CR rate (0.54 (95% CI 0.42-0.69) vs bispecific antibodies 0.35 (0.30-0.41), p<0.01) and pooled ORR (0.83 (0.76-0.90) vs 0.65 (0.59-0.71), p<0.01). However, CAR-T therapy had a higher incidence of adverse events, particularly cytokine release syndrome (CRS 0.83 (0.70-0.97) vs bispecific antibodies 0.59 (0.43-0.74), p<0.05). Severe CRS (grade ≥3) occurred at a rate of 0.07 (0.03-0.14) in the CAR-T cell group, contrasting with a negligible rate of 0.01 (0.00-0.02) in the bispecific antibody group (p<0.01). Hematologic adverse events, including neutropenia (grade ≥3; 0.88 (0.81-0.95) vs 0.48 (0.30-0.67), p<0.01) and anemia (grade≥3; 0.55 (0.47-0.62) vs 0.34 (0.28 to 0.40), p<0.01), were also more frequent in the CAR-T-cell group. Furthermore, differences in efficacy were observed among various CAR-T products, with ciltacabtagene autoleucel showing greater efficacy in CR rate (0.77 (0.71-0.84) vs 0.37 (0.32-0.41), p<0.01) and ORR (0.91 (0.83-0.99) vs 0.73 (0.68-0.77), p<0.01) compared with idecabtagene vicleucel.
CONCLUSION
CAR-T-cell therapy demonstrated superior CR rates compared with bispecific antibodies, although with an increase in severe adverse events.
背景
嵌合抗原受体 T 细胞疗法和双特异性抗体已经彻底改变了多发性骨髓瘤的治疗格局。然而，目前缺乏比较这两种方法疗效和安全性的研究。本荟萃分析评估了 B 细胞成熟抗原（BCMA）导向的嵌合抗原受体 T 细胞疗法和 BCMA×CD3 双特异性抗体作为三线或三线以上治疗复发/难治性多发性骨髓瘤（RRMM）的疗效和安全性。
方法
我们检索了 PubMed、Embase、Web of Science 和 Cochrane 数据库，截至 2024 年 5 月 31 日，共纳入了 11 项符合条件的研究，涵盖了 1269 名参与者。随机效应模型评估了主要（完全缓解率（CR 率））和次要（总体缓解率（ORR））结局，同时进行了元回归分析以调整相关协变量。
结果
嵌合抗原受体 T 细胞疗法的总体 CR 率（0.54（95%CI 0.42-0.69）vs 双特异性抗体 0.35（0.30-0.41），p<0.01）和总体 ORR（0.83（0.76-0.90）vs 0.65（0.59-0.71），p<0.01）均显著更高。然而，嵌合抗原受体 T 细胞疗法的不良反应发生率更高，特别是细胞因子释放综合征（CRS）（0.83（0.70-0.97）vs 双特异性抗体 0.59（0.43-0.74），p<0.05）。CAR-T 细胞组的严重 CRS（等级≥3）发生率为 0.07（0.03-0.14），而双特异性抗体组的发生率可忽略不计，为 0.01（0.00-0.02）（p<0.01）。血液学不良反应，包括中性粒细胞减少症（等级≥3；0.88（0.81-0.95）vs 0.48（0.30-0.67），p<0.01）和贫血症（等级≥3；0.55（0.47-0.62）vs 0.34（0.28 至 0.40），p<0.01）在 CAR-T 细胞组也更为常见。此外，不同的 CAR-T 产品在疗效方面存在差异，cilta-cabtagene autoleucel 在 CR 率（0.77（0.71-0.84）vs 0.37（0.32-0.41），p<0.01）和 ORR（0.91（0.83-0.99）vs 0.73（0.68-0.77），p<0.01）方面表现出更大的疗效，与 idecabtagene vicleucel 相比。
结论
与双特异性抗体相比，嵌合抗原受体 T 细胞疗法显示出更高的 CR 率，但严重不良反应发生率增加。
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