肿瘤细胞治疗研究
英文原题：CAR T-cells vs. bispecific antibodies as third- or later-line treatment for relapsed/refractory follicular lymphoma: a literature review and meta-analysis.
我们的荟萃分析提示，在 R/R FL 中，CAR-T 细胞疗法相比双特异性抗体（BsAb）呈现出疗效结局改善的趋势，缓解率更高、PFS 更长。
背景：复发/难治性滤泡性淋巴瘤（R/R FL）仍是肿瘤学重大挑战，尤其对于已用尽标准治疗选择的患者。CAR-T细胞疗法和双特异性抗体（BsAb）均已成为该情境下有前景的治疗方式，提供新作用机制及改善结局的可能性。然而，两者疗效和安全性的比较数据有限。本研究旨在评估CAR-T与BsAb作为R/R FL三线及以后治疗的临床结局和安全性。方法：开展系统综述与荟萃分析，比较R/R FL患者CAR-T和BsAb治疗的疗效与安全性。依据预设纳入标准筛选研究，提取相关数据，评估总缓解率（ORR）、完全缓解（CR）率、无进展生存期（PFS）及不良事件发生率，包括细胞因子释放综合征（CRS）和神经毒性。采用随机效应模型进行统计分析，以考虑研究间差异。结果：分析纳入12项研究，共1,200例患者。与BsAb相比，CAR-T疗效更高：ORR为92% vs 77%（95% CI 0.77–0.90，P=.01），CR率为82% vs 65%（95% CI 0.65–0.80，P<.001）。CAR-T治疗PFS中位数为15个月，显著长于BsAb的9个月。CAR-T组不良事件更多，尤其是神经毒性（7%；95% CI 0.02–0.13）。但总体安全性可管理，多数不良事件为1–2级。BsAb严重不良事件发生率较低，但疗效相对较差。结论：荟萃分析提示，与双特异性抗体相比，CAR-T治疗R/R FL的疗效可能更佳，表现为更高缓解率和更长PFS。但由于各研究在基线肿瘤负荷、既往治疗线次、既往治疗耐药情况及桥接治疗方案方面可能不均衡，需谨慎解读这一优势。CAR-T治疗的严重不良事件发生率较高，尤其是神经毒性。结果表明CAR-T是一种有前景的治疗策略，但其比较获益仍需在风险匹配、方案标准化的研究中验证。未来研究应优先探索风险适配的治疗选择及高危人群毒性缓解策略。系统综述注册：PROSPERO CRD420251107275。
BACKGROUND: Relapsed/refractory follicular lymphoma (R/R FL) remains a significant challenge in oncology, particularly for patients who have exhausted standard treatment options. Both chimeric antigen receptor (CAR) T-cell therapy and bispecific antibodies(BsAb) have emerged as promising therapeutic modalities in this setting, offering novel mechanisms of action and the potential for improved outcomes. However, comparative data on the efficacy and safety of these treatments remain limited. This study aims to evaluate the clinical outcomes and safety profiles of CAR T-cell therapy versus BsAb as third- or later-line treatments for R/R FL. METHODS: A systematic review and meta-analysis were conducted to compare the efficacy and safety of CAR T-cell therapy and BsAb in patients with R/R FL. Studies were selected based on predefined inclusion criteria, and relevant data were extracted to assess overall response rates (ORR), complete remission (CR) rates, progression-free survival (PFS), and the incidence of adverse events, including cytokine release syndrome (CRS) and neurotoxicity. Statistical analyses were performed using random-effects models to account for variability across studies. RESULTS: The analysis included 12 studies, with a total of 1,200 patients. CAR T-cell therapy demonstrated superior efficacy compared to BsAb, with a higher ORR (92% vs. 77%)[95% confidence interval (CI) 0.77-0.90] (p= 0.01)and CR rate (82% vs. 65%) [95% CI 0.65-0.80] (p< 0.001). The median PFS was significantly longer for CAR T-cell therapy (15 months) compared to BsAb (9 months). Adverse events were more common in the CAR T-cell group, particularly neurotoxicity (7%[95% CI 0.02-0.13]). However, the overall safety profile was manageable, with most adverse events being grade 1-2 in severity. BsAb were associated with a lower incidence of severe adverse events but showed less favorable efficacy outcomes. CONCLUSIONS: Our meta-analysis suggests that CAR T-cell therapy demonstrates a trend toward improved efficacy outcomes compared to bispecific antibodies (BsAb) in R/R FL, with higher response rates and longer PFS. However, this observed advantage must be interpreted cautiously due to potential confounders, including imbalances in baseline tumor burden, prior treatment lines, refractoriness to prior therapy, and variations in bridging therapy protocols across studies. Notably, CAR T-cell therapy was associated with a higher incidence of severe adverse events, particularly neurotoxicity. These findings indicate that while CAR T-cell therapy represents a promising therapeutic strategy, its comparative benefits require validation in studies with matched risk populations and standardized protocols. Future research should prioritize risk-adapted treatment selection and toxicity mitigation strategies for high-risk cohorts. SYSTEMATIC REVIEW REGISTRATION: https://www.crd.york.ac.uk/PROSPERO/view/CRD420251107275, Identifier CRD420251107275.
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