肿瘤细胞治疗研究
英文原题：Salvage outcomes with teclistamab after BCMA-directed therapy failure in relapsed/refractory multiple myeloma: a systematic review and meta-analysis.
Teclistamab在BCMA治疗失败后显示出有意义的活性，可能代表一种挽救选择。然而，鉴于证据确定性为低至极低，疗效估计必须谨慎解读。需要前瞻性生物标志物分层试验，以优化BCMA靶向序列并识别最可能获益的患者。
尽管治疗取得了进展，多发性骨髓瘤仍然是一种治疗上具有挑战性的疾病。虽然 BCMA 靶向治疗改善了结局，但复发后尚无标准方案。Teclistamab 是一种 BCMA × CD3 双特异性抗体，可将 T 细胞重定向以裂解骨髓瘤细胞，并可能克服对既往 BCMA 靶向治疗的耐药性。
我们按照PRISMA指南进行了系统综述和meta分析，检索了主要数据库自建库至2025年11月的文献。纳入既往接受过BCMA靶向治疗（BDT）后接受teclistamab治疗的复发/难治性多发性骨髓瘤（RRMM）成人患者。主要结局为总缓解率（ORR）、完全缓解（CR）率、非常好的部分缓解（VGPR）和部分缓解（PR）。次要结局为无进展生存期（PFS）、总生存期（OS）和1年总生存率（1-year OS）。采用随机效应模型合并缓解比例，使用GRADE评估证据质量，重建Kaplan-Meier曲线以比较BDT暴露与BDT初治队列之间的生存差异。
纳入9项观察性研究，共718例BDT暴露患者。Teclistamab达到汇总ORR为56%（95% CI：50-63；I²=73%），CR率为22%（95% CI：17%-27%；I²=0%）。VGPR率为20%（95% CI：15%-27%）。在既往接受过CAR-T治疗的患者中（n=371），ORR为58%（95% CI：47%-69%；CR 29%），而既往接受过ADC治疗的患者（n=114）ORR为64%（95% CI：50%-76%；CR 19%）。BDT暴露患者的中位PFS为101天，而BDT未暴露患者为220天（BDT未暴露 vs. 暴露的HR=0.47，95% CI：0.39-0.56；p<0.01），而两组的中位OS相当（每组均为437天；HR=1.00；p=0.997）。感染发生于44.6%的患者，任何级别CRS发生于57.9%（≥3级，1.3%），中性粒细胞减少发生于32.3%。由于高偏倚风险、异质性和间接性，大多数结局的总体GRADE证据确定性为低至极低。
BACKGROUND: Despite advances in treatments multiple myeloma remains a therapeutically challenging disease. Although BCMA-directed therapies have improved outcomes, no standard exists after relapse. Teclistamab, a BCMA × CD3 bispecific antibody, redirects T cells to lyse myeloma cells and may overcome resistance to prior BCMA-targeting therapies. METHODS: We conducted a systematic review and meta-analysis according to PRISMA guidelines, searching major databases from inception through November 2025. Adults with relapsed/refractory multiple myeloma (RRMM) who received teclistamab after prior BCMA-directed therapy (BDT) were included. Primary outcomes were overall response rate (ORR), complete response (CR) rate, very good partial response (VGPR), and partial response (PR). Secondary outcomes were progression-free survival (PFS), overall survival (OS), and one-year overall survival (1-year OS). Response proportions were pooled using random-effects models, evidence was assessed using the GRADE, Kaplan-Meier curves were reconstructed to compare the survival between BDT-exposed and BDT-naive cohorts. RESULTS: Nine observational studies including 718 BDT-exposed patients were included., Teclistamab achieved a pooled ORR of 56% (95% CI: 50-63; I²=73%), with a CR rate of 22% (95% CI: 17%-27%; I² = 0%). VGPR rate was 20% (95% CI: 15%-27%). Among prior CAR-T recipients (n = 371), ORR was 58% (95% CI: 47%-69%; CR 29%), while prior ADC recipients (n = 114) had an ORR of 64% (95% CI: 50%-76%; CR 19%). BDT-exposed patients had a median PFS of 101 days compared with 220 days in BDT-naive patients (HR for BDT-naive vs. exposed = 0.47, 95% CI: 0.39-0.56; p < 0.01), whereas median OS was comparable between groups (437 days in each group; HR = 1.00; p = 0.997). Infections occurred in 44.6% of patients, any-grade CRS in 57.9% (grade ≥3, 1.3%), neutropenia in 32.3%. The overall GRADE certainty of evidence was low to very low across most outcomes due to high risk of bias, heterogeneity, and indirectness. CONCLUSION: Teclistamab shows meaningful activity after BCMA therapy failure and may represent a salvage option. However, efficacy estimates must be interpreted with caution given the low to very low certainity of evidence. Prospective biomarker-stratified trials are needed to optimize BCMA-targeting sequences and identify patients most likely to benefit.
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