双特异性抗体治疗复发或难治性多发性骨髓瘤的疗效和安全性：前瞻性临床试验的系统评价和荟萃分析。

Efficacy and safety of bispecific antibodies therapy for relapsed or refractory multiple myeloma: a systematic review and meta-analysis of prospective clinical trials.

机构信息

Department of Hematology, West China Hospital, Sichuan University, Chengdu, China.

出版信息

Front Immunol. 2024 Feb 28;15:1348955. doi: 10.3389/fimmu.2024.1348955. eCollection 2024.

DOI:10.3389/fimmu.2024.1348955

PMID:38482019

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10933024/

Abstract

OBJECTIVE

Bispecific antibody (BsAbs) therapy represents a promising immunotherapeutic approach with manageable toxicity and noteworthy preliminary efficacy in treating patients with relapsed or refractory multiple myeloma (RRMM). The objective of this systematic review and meta-analysis was to compare the efficacy and safety of B-cell maturation antigen (BCMA)-targeted BsAbs and non-BCMA-targeted BsAbs in the treatment of RRMM patients.

METHODS

PubMed/MEDLINE, Web of Science, EMBASE, Cochrane Library and meeting libraries were searched from inception to August 16th, 2023. The efficacy evaluation included the complete objective response rate (ORR), complete response (CR) rate, stringent CR (sCR) rate, partial response (PR) rate, and very good PR (VGPR) rate. The efficacy evaluation included any grade adverse events (AEs) and grade ≥ 3 AEs.

RESULTS

Fourteen studies with a total of 1473 RRMM patients were included. The pooled ORR of the entire cohort was 61%. The non-BCMA-targeted BsAbs group displayed a higher ORR than the BCMA-targeted BsAbs group (74% . 54%, < 0.01). In terms of hematological AEs, BCMA-targeted BsAbs therapy exhibited higher risks of neutropenia (any grade: 48% . 18%, < 0.01; grade ≥ 3: 43% . 15%, < 0.01) and lymphopenia (any grade: 37% . 8%, < 0.01; grade ≥ 3: 31% . 8%, = 0.07). Regarding non-hematological AEs, there were no significant differences in the risks of cytokine release syndrome (CRS, any grade: 64% . 66%, = 0.84; grade ≥ 3: 1% . 1%, = 0.36) and infections (any grade: 47% . 49%, = 0.86; grade ≥ 3: 24% . 20%, = 0.06) between the two groups. However, non-BCMA-targeted BsAbs therapy was associated with a higher risk of immune effector cell-associated neurotoxicity syndrome (ICANS, any grade: 11% . 2%, < 0.01) and lower risks of fatigue (any grade: 14% . 30%, < 0.01) and pyrexia (any grade: 14% . 29%, < 0.01).

CONCLUSION

This analysis suggest that non-BCMA-targeted BsAbs therapy may offer a more favorable treatment response and tolerability, while BCMA-targeted BsAbs therapy may be associated with diminished neurotoxic effects.

SYSTEMATIC REVIEW REGISTRATION

https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42018090768.

摘要

目的

双特异性抗体（BsAb）疗法代表了一种有前途的免疫治疗方法，具有可管理的毒性和在治疗复发/难治性多发性骨髓瘤（RRMM）患者中显著的初步疗效。本系统评价和荟萃分析的目的是比较针对 B 细胞成熟抗原（BCMA）的 BsAb 与非 BCMA 靶向的 BsAb 在 RRMM 患者治疗中的疗效和安全性。

方法

从成立到 2023 年 8 月 16 日，检索了 PubMed/MEDLINE、Web of Science、EMBASE、Cochrane 图书馆和会议文库。疗效评估包括完全客观缓解率（ORR）、完全缓解（CR）率、严格 CR（sCR）率、部分缓解（PR）率和非常好的 PR（VGPR）率。疗效评估包括任何级别不良事件（AE）和≥3 级 AE。

结果

共纳入了 14 项研究，共计 1473 例 RRMM 患者。整个队列的汇总 ORR 为 61%。非 BCMA 靶向的 BsAb 组的 ORR 高于 BCMA 靶向的 BsAb 组（74% vs 54%，<0.01）。在血液学 AE 方面，BCMA 靶向的 BsAb 治疗组中性粒细胞减少症（任何级别：48% vs 18%，<0.01；≥3 级：43% vs 15%，<0.01）和淋巴细胞减少症（任何级别：37% vs 8%，<0.01；≥3 级：31% vs 8%，=0.07）的风险更高。关于非血液学 AE，细胞因子释放综合征（CRS，任何级别：64% vs 66%，=0.84；≥3 级：1% vs 1%，=0.36）和感染（任何级别：47% vs 49%，=0.86；≥3 级：24% vs 20%，=0.06）的风险在两组之间无显著差异。然而，非 BCMA 靶向的 BsAb 治疗与免疫效应细胞相关神经毒性综合征（ICANS，任何级别：11% vs 2%，<0.01）的风险较高以及疲劳（任何级别：14% vs 30%，<0.01）和发热（任何级别：14% vs 29%，<0.01）的风险较低相关。