肿瘤细胞治疗研究
英文原题：Cytokine Release Syndrome and Immune Effector Cell-Associated Neurotoxicity Syndrome Following Axicabtagene Ciloleucel or Brexucabtagene Autoleucel Chimeric Antigen Receptor T-Cell Therapy: Center for International Blood and Marrow Transplant Research Data.
纳入了87个美国中心的927名患者（axi-cel， n = 707 [76.3%]； brexu-cel， n = 220 [23.7%]）。
靶向CD19的CAR-T 细胞疗法已在复发/难治性B细胞恶性肿瘤的治疗中显示出有效性。美国已批准多种CAR-T疗法，包括axicabtagene ciloleucel（axi-cel）用于复发/难治性弥漫大B细胞淋巴瘤（DLBCL），以及brexucabtagene autoleucel（brexu-cel）用于B细胞前体急性淋巴细胞白血病和套细胞淋巴瘤（MCL）。然而，CAR-T疗法的使用可能导致潜在严重的不良反应，如细胞因子释放综合征（CRS）和免疫效应细胞相关神经毒性综合征（ICANS）。本项真实世界数据分析评估了B细胞恶性肿瘤患者接受axi-cel或brexu-cel治疗后CRS和ICANS的发生率及管理情况。这项回顾性观察性队列研究分析了国际血液和骨髓移植研究中心（CIBMTR）的数据。纳入标准为2020年10月至2021年12月期间在美国接受axi-cel或brexu-cel治疗任何适应症的成年患者，且至少有1次随访。主要关注结局为CAR-T治疗后CRS和ICANS的发生率，按照美国移植与细胞治疗学会（ASTCT）指南进行分级。同时研究了CRS和ICANS的预防性治疗管理以及CRS和ICANS发生后所给予的治疗。总体而言，共纳入来自87个美国中心的927例患者（axi-cel，n = 707 [76.3%]；brexu-cel，n = 220 [23.7%]）。中位（范围）年龄为63（19至89）岁，65.3%（605/927）为男性。大多数患者（83.3% [n = 589]）因DLBCL或转化型滤泡性淋巴瘤接受axi-cel治疗。所有接受brexu-cel的患者均患有MCL。总体而言，766例（82.6%）患者发生了CRS（2级，47.0%；766例中360例）。在有可用数据的患者中，12.4%（715例中89例）接受了CRS预防治疗，最常见的是单用tocilizumab（79.8%；89例中71例）。在发生CRS的患者中，76.6%（766例中587例）接受了CRS治疗，包括1级患者中的63.5%（406例中258例）和2级患者中的91.4%（360例中329例）。最常见的治疗是tocilizumab（97.3%；587例中571例），单用或联合使用。在有可用数据的患者中，49.8%（715例中356例）接受了ICANS预防，大多数为单用抗癫痫药（93.3%；356例中332例）。在876例可评估患者中，424例（48.4%）发生了ICANS（2级，71.5%；424例中303例）。其中，85.6%（424例中363例）接受了ICANS治疗，最常见的是皮质类固醇（92.3%；363例中335例）。CRS（82.6%）和ICANS（48.4%）的发生率与根据axi-cel和brexu-cel处方信息预期的发生率一致，突显了CAR-T治疗的潜在负担。这些结果还强调了在CAR-T治疗期间持续进行患者监测和管理的重要性，并展示了不断演变的治疗格局，包括对CRS更积极的管理以及对CRS和ICANS预防性治疗的关注。
Chimeric antigen receptor T-cell (CAR-T) therapies targeting CD19 have demonstrated effectiveness in the treatment of relapsed/refractory B-cell malignancies. Several CAR-T therapies have been approved in the United States, including axicabtagene ciloleucel (axi-cel), for relapsed/refractory diffuse large B-cell lymphoma (DLBCL), and brexucabtagene autoleucel (brexu-cel), for B-cell precursor acute lymphoblastic leukemia and mantle cell lymphoma (MCL). However, use of CAR-T therapies can result in potentially severe adverse effects such as cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS). This analysis of real-world data evaluated the incidence and management of CRS and ICANS in patients with B-cell malignancies following treatment with axi-cel or brexu-cel therapy. This retrospective observational cohort study analyzed data from the Center for International Blood and Marrow Transplant Research (CIBMTR). Adult patients in the United States who received axi-cel or brexu-cel for any indication from October 2020 to December 2021 with 1 follow-up visit were included. The main outcome of interest was incidence of CRS and ICANS following CAR-T therapy, graded according to the American Society for Transplantation and Cellular Therapy (ASTCT) guidelines. Management of CRS and ICANS with preventive therapies and treatments administered following development of CRS and ICANS was also investigated. Overall, 927 patients across 87 US centers were included (axi-cel, n = 707 [76.3%]; brexu-cel, n = 220 [23.7%]). Median (range) age was 63 (19 to 89) years, and 65.3% (605/927) were male. Most patients (83.3% [n = 589]) received axi-cel for DLBCL or transformed follicular lymphoma. All patients who received brexu-cel had MCL. Overall, 766 (82.6%) patients developed CRS (grade 2, 47.0%; 360 of 766). Of patients with available data, 12.4% (89 of 715) received CRS preventive therapy, most commonly with tocilizumab alone (79.8%; 71 of 89). Of patients who developed CRS, 76.6% (587 of 766) received CRS treatment, including 63.5% (258 of 406) of patients with grade 1 and 91.4% (329 of 360) with grade 2. The most common treatment was tocilizumab (97.3%; 571 of 587), alone or in combination. Of patients with available data, 49.8% (356 of 715) received ICANS prevention, mostly anti-epileptics alone (93.3%; 332 of 356). Of 876 evaluable patients, 424 (48.4%) developed ICANS (grade 2, 71.5%; 303 of 424). Of these, 85.6% (363 of 424) received treatment for ICANS, most commonly corticosteroids (92.3%; 335 of 363). Rates of CRS (82.6%) and ICANS (48.4%) were consistent with incidences expected based on prescribing information for axi-cel and brexu-cel, highlighting potential burdens of CAR-T therapy. These results also stress the importance of continuous patient monitoring and management during CAR-T therapy and demonstrate an evolving treatment landscape, including more aggressive management of CRS and interest in preventive therapies for CRS and ICANS.
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