肿瘤细胞治疗研究
英文原题：Efficacy and safety of frail patients treated with ciltacabtagene autoleucel in the real world: A Center for International Blood and Marrow Transplant Research analysis.
Cilta-cel 在 frail RRMM 中仍然有效，但 frailty 与生存期缩短和毒性增加相关，支持制定个体化的 CAR-T 策略。
西达基奥仑赛（cilta-cel）是一种靶向B细胞成熟抗原（BCMA）的CAR-T 细胞疗法，已获批用于复发/难治性多发性骨髓瘤（RRMM）。
利用国际血液和骨髓移植研究中心登记处，本研究评估了2022年3月至2023年12月期间接受商业cilta-cel治疗的虚弱患者的结果。虚弱通过一个结合年龄、体能状态和合并症的适应性简化评分来定义。
在541例有衰弱状态数据的患者中，183例（33.8%）为衰弱，358例（66.2%）为非衰弱。总体缓解率相当（衰弱组82.8% vs. 非衰弱组88.5%）。然而，衰弱患者的无进展生存期（PFS）较差（12个月PFS，62.7% [95% CI，53.6%-71.3%] vs. 75.9% [95% CI，70.4%-81.1%]；p < .01）和总生存期（OS）较差（12个月OS 72.8% [95% CI，64.9%-80.0%] vs. 90.4% [95% CI，86.6%-93.7%]；p < .01）。衰弱患者12个月治疗相关死亡率为6.8%（95% CI，3.4%-11.2%），而非衰弱患者为3.6%（95% CI，1.8%-6.1%），p = .12。细胞因子释放综合征（≥2级）在衰弱患者中发生率为22.4%，非衰弱患者为17.9%（p = .05），任何级别的免疫效应细胞相关神经毒性（ICANS）报告率分别为32.2% vs. 17.6%（p < .01）。颅神经麻痹和帕金森综合征的发生率相当。持续性血细胞减少（>第30天）在衰弱患者中更常见（30.6% vs. 21.2%；p < .01）。在多变量分析中，衰弱独立预测较差的PFS（风险比[HR]，1.67；95% CI，1.16-2.40）、OS（HR，2.46；95% CI，1.57-3.87）以及任何级别ICANS的更高几率（比值比，2.01；95% CI，1.32-3.08）（均p < .01）。
BACKGROUND: Ciltacabtagene autoleucel (cilta-cel), an anti-B-cell maturation antigen (BCMA) chimeric antigen receptor T-cell (CAR-T) therapy, is approved for relapsed/refractory multiple myeloma (RRMM). METHODS: Using the Center for International Blood and Marrow Transplant Research registry, this study evaluated outcomes of frail patients receiving commercial cilta-cel from March 2022 to December 2023. Frailty was defined by an adapted simplified score incorporating age, performance status, and comorbidities. RESULTS: Among 541 patients with available frailty status, 183 (33.8%) were frail and 358 (66.2%) were nonfrail. Overall response rates were comparable (frail 82.8% vs. nonfrail 88.5%). However, frail patients had inferior progression-free survival (PFS) (12-month PFS, 62.7% [95% confidence interval (CI), 53.6%-71.3%] vs. 75.9% [95% CI, 70.4%-81.1%]; p < .01) and overall survival (OS) (12-month OS 72.8% [95% CI, 64.9%-80.0%] vs. 90.4% [95% CI, 86.6%-93.7%]; p < .01). Twelve-month treatment-related mortality in frail patients was 6.8% (95% CI, 3.4%-11.2%) versus 3.6% (95% CI, 1.8%-6.1%), p = .12. Cytokine release syndrome (grade ≥2) occurred in 22.4% of frail versus 17.9% of nonfrail patients (p = .05), and immune effector cell-associated neurotoxicity (ICANS) of any grade was reported in 32.2% versus 17.6% (p < .01). Rates of cranial nerve palsies and Parkinsonism were comparable. Prolonged cytopenia (>day 30) was more common in frail patients (30.6% vs. 21.2%; p < .01). On multivariable analysis, frailty independently predicted worse PFS (hazard ratio [HR], 1.67; 95% CI, 1.16-2.40), OS (HR, 2.46; 95% CI, 1.57-3.87), and higher odds of any-grade ICANS (odds ratio, 2.01; 95% CI, 1.32-3.08) (all p < .01). CONCLUSIONS: Cilta-cel remains effective in frail RRMM, but frailty is associated with reduced survival and increased toxicity, supporting tailored CAR-T strategies.
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