双特异性抗体(BsAbs)疗法代表了一种有希望的免疫治疗方法,在治疗复发性或难治性多发性骨髓瘤(RRMM)患者中具有可控制的毒性和显著的初步功效。本系统评价和荟萃分析的目的是比较B细胞成熟抗原(BCMA)靶向BsAb和非BCMA靶向BsAb在RRMM患者治疗中的疗效和安全性。
■PubMed/MEDLINE,WebofScience,EMBASE,从成立到8月16日,搜索了Cochrane图书馆和会议图书馆,2023年。疗效评价包括完全客观缓解率(ORR),完全反应(CR)率,严格的CR(sCR)率,部分响应(PR)率,和非常好的PR(VGPR)率。疗效评价包括任何等级不良事件(AE)和≥3级AE。
■纳入14项研究,共1473例RRMM患者。整个队列的合并ORR为61%。非BCMA靶向BsAbs组的ORR高于BCMA靶向BsAbs组(74%vs.54%,P<0.01)。就血液学不良事件而言,BCMA靶向BsAb治疗表现出更高的中性粒细胞减少症风险(任何级别:48%vs.18%,P<0.01;≥3级:43%vs.15%,P<0.01)和淋巴细胞减少(任何等级:37%vs.8%,P<0.01;≥3级:31%vs.8%,P=0.07)。关于非血液学不良事件,细胞因子释放综合征(CRS,任何等级:64%vs.66%,P=0.84;等级≥3:1%vs.1%,P=0.36)和感染(任何等级:47%vs.49%,P=0.86;≥3级:24%vs.20%,两组之间P=0.06)。然而,非BCMA靶向BsAb治疗与免疫效应细胞相关神经毒性综合征的高风险相关(ICANS,任何等级:11%vs.2%,P<0.01)和更低的疲劳风险(任何等级:14%vs.30%,P<0.01)和发热(任何等级:14%vs.29%,P<0.01)。
■该分析表明,非BCMA靶向BsAb治疗可能会提供更有利的治疗反应和耐受性,而BCMA靶向BsAb治疗可能与减少的神经毒性作用有关。
■https://www.crd.约克。AC.英国/PROSPERO/,标识符CRD42018090768。
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.
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.
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% vs. 54%, P < 0.01). In terms of hematological AEs, BCMA-targeted BsAbs therapy exhibited higher risks of neutropenia (any grade: 48% vs. 18%, P < 0.01; grade ≥ 3: 43% vs. 15%, P < 0.01) and lymphopenia (any grade: 37% vs. 8%, P < 0.01; grade ≥ 3: 31% vs. 8%, P = 0.07). Regarding non-hematological AEs, there were no significant differences in the risks of cytokine release syndrome (CRS, any grade: 64% vs. 66%, P = 0.84; grade ≥ 3: 1% vs. 1%, P = 0.36) and infections (any grade: 47% vs. 49%, P = 0.86; grade ≥ 3: 24% vs. 20%, P = 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% vs. 2%, P < 0.01) and lower risks of fatigue (any grade: 14% vs. 30%, P < 0.01) and pyrexia (any grade: 14% vs. 29%, P < 0.01).
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.
https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42018090768.