肿瘤细胞治疗研究
英文原题：Efficacy and Safety of CAR-T Cell Therapy and Bispecific Antibodies in Relapsed/Refractory Multiple Myeloma with Renal Impairment: A Propensity Score-Matched Analysis.
在这项回顾性分析中，肾功能不全与RRMM患者接受CAR-T治疗或BsAb治疗后的生存结局较差无关，提示仅存在RI不应成为排除使用这些药物的理由。然而，RI与血液学毒性增加和AKI风险升高相关，需要加强支持治疗和监测。这些发现支持在适当监测下扩大RI患者接受T细胞重定向免疫治疗的可及性，但仍需前瞻性验证。
T细胞重定向免疫疗法，包括CAR-T 细胞疗法和双特异性抗体（BsAbs），已改变了复发/难治性多发性骨髓瘤（RRMM）的治疗格局。然而，关键注册试验通常排除了伴有显著肾功能损害（RI）的患者，在诊断时肾脏疾病影响20-50%患者的这一人群中造成了关键性证据空白。目前缺乏对两种治疗方式在不同估算肾小球滤过率（eGFR）范围内结局的直接比较。
我们使用TriNetX全球协作网络（一个联邦电子健康记录研究平台）进行了一项回顾性队列研究。接受CAR-T疗法（idecabtagene vicleucel或ciltacabtagene autoleucel）或BsAbs（teclistamab、elranatamab或talquetamab）治疗的RRMM成人患者按基线肾功能分层：重度RI（eGFR <30 mL/min/1.73 m²）、中度RI（eGFR 30-60 mL/min/1.73 m²）和肾功能保留（eGFR >60 mL/min/1.73 m²）。对每种治疗类型内的每项比较，均进行了倾向评分匹配（PSM）（1:1），并针对关键临床和人口学协变量进行了调整。在1年、2年和3年时评估长期结局（全因死亡率和至下一次治疗时间[TTNT]）。此外，使用Kaplan-Meier分析评估总生存期（OS）。在1个月、3个月和6个月时评估短期安全性结局。
共识别出2716例CAR-T受者和3376例BsAb受者。匹配后，在CAR-T队列中分析了281对（重度RI vs. 保留）和878对（中度RI vs. 保留）；在BsAb队列中分别分析了645对和1158对。无论是CAR-T还是BsAb治疗，重度或中度RI均与死亡率增加或TTNT缩短无显著相关性。然而，在两种治疗方式中，RI患者的贫血、血小板减少和急性肾损伤（AKI）发生率均显著更高。细胞因子释放综合征（CRS）、免疫效应细胞相关神经毒性综合征（ICANS）和中性粒细胞减少发生率在各肾功能分层间相当。在BsAb队列中，重度RI组感染在1个月时短暂升高（RR 1.29；95% CI 1.06-1.58；p = 0.011），但到3个月时趋于均衡。
BACKGROUND/OBJECTIVES: T-cell-redirecting immunotherapies, including chimeric antigen receptor T-cell (CAR-T) therapy and bispecific antibodies (BsAbs), have transformed the treatment of relapsed/refractory multiple myeloma (RRMM). However, pivotal registration trials routinely excluded patients with significant renal impairment (RI), creating a critical evidence gap in a population where kidney disease affects 20-50% of patients at diagnosis. Direct comparisons of outcomes across the estimated glomerular filtration rate (eGFR) spectrum for both modalities are lacking. METHODS: We conducted a retrospective cohort study using the TriNetX Global Collaborative Network, a federated electronic health record research platform. Adult patients with RRMM treated with CAR-T therapy (idecabtagene vicleucel or ciltacabtagene autoleucel) or BsAbs (teclistamab, elranatamab, or talquetamab) were stratified by baseline renal function: severe RI (eGFR <30 mL/min/1.73 m 2 ), moderate RI (eGFR 30-60 mL/min/1.73 m 2 ), and preserved renal function (eGFR >60 mL/min/1.73 m 2 ). Propensity score matching (PSM) (1:1), adjusted for key clinical and demographic covariates, was performed for each comparison within each therapy type. Long-term outcomes (all-cause mortality and time to next treatment [TTNT]) were assessed at 1, 2, and 3 years. Overall survival (OS) was additionally evaluated using Kaplan-Meier analysis. Short-term safety outcomes were assessed at 1, 3, and 6 months. RESULTS: A total of 2716 CAR-T and 3376 BsAb recipients were identified. After matching, 281 pairs (severe RI vs. preserved) and 878 pairs (moderate RI vs. preserved) were analyzed in the CAR-T cohort; 645 and 1158 pairs, respectively, were analyzed in the BsAb cohort. Neither severe nor moderate RI was significantly associated with increased mortality or shorter TTNT after either CAR-T or BsAb therapy. However, patients with RI experienced significantly higher rates of anemia, thrombocytopenia, and acute kidney injury (AKI) across both modalities. Cytokine release syndrome (CRS), immune effector cell-associated neurotoxicity syndrome (ICANS), and neutropenia rates were comparable across renal strata. In the BsAb cohort, infections were transiently elevated at 1 month in the severe RI group (RR 1.29; 95% CI 1.06-1.58; p = 0.011) but equilibrated by 3 months. CONCLUSIONS: In this retrospective analysis, renal impairment was not associated with inferior survival outcomes following CAR-T therapy or BsAb treatment in RRMM, suggesting that RI alone should not preclude the use of these agents. However, RI conferred increased hematologic toxicity and AKI risk, warranting enhanced supportive care and monitoring. These findings support broadening access to T-cell-redirecting immunotherapies for patients with RI with appropriate surveillance, though prospective validation is needed.
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