CAR-T(CAR-T)细胞疗法在非肿瘤性疾病中的应用
Chimeric antigen receptor T (CAR-T) cell therapy in non-oncological diseases.
CAR-T(CAR-T)细胞在血液系统恶性肿瘤中的应用推动了这种免疫治疗形式的显著进展。
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Features and outcomes of patients admitted to the ICU for chimeric antigen receptor T cell-related toxicity: a French multicentre cohort.
Features and outcomes of patients admitted to the ICU for chimeric antigen receptor T cell-related toxicity: a French multicentre cohort.
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CAR-T 治疗后入住 ICU 很常见,通常是为了处理特定的毒性反应。我们的经验令人鼓舞,尽管 3-4 级毒性反应发生率高,但 ICU 死亡率低,且半数患者在一年时仍存活并处于完全缓解状态。
CAR-T 细胞治疗越来越多地用于难治性血液系统恶性肿瘤患者,但可诱发严重不良事件。我们旨在描述CAR-T 治疗后入住重症监护室(ICU)患者的临床特征和结局。
这项回顾性观察性队列研究纳入了2018-2022年间在CAR-T 治疗后的3个月内入住两家法国ICU中任意一家的连续成人患者。
在238例接受CAR-T 治疗的患者中,84例(35.3%)需要入住ICU并被纳入研究,入住时间为CAR-T 输注后中位5 [0-7]天。中位SOFA和SAPSII评分分别为3 [2-6]和39 [30-48]。80/84例(95.2%)患者符合细胞因子释放综合征标准,其中18/80例(22.5%)为3-4级毒性。免疫效应细胞相关神经毒性综合征(ICANS)发生于46/84例(54.8%)患者,其中29/46例(63%)为3-4级毒性。15/84例(17.9%)患者诊断为噬血细胞性淋巴组织细胞增生症。73/84例(86.9%)患者使用了托珠单抗,中位剂量为2 [1-4]次。55/84例(65.5%)患者接受了类固醇治疗,其中21/55例(38.2%)接受了大剂量冲击治疗。总体而言,23/84例(27.4%)患者发生细菌感染,3/84例(3.6%)发生真菌感染(1例侵袭性肺曲霉病和2例毛霉目感染),2例(2.4%)发生巨细胞病毒感染。23/84例(27.4%)需要使用血管升压药,12/84例(14.3%)需要有创机械通气,4/84例(4.8%)需要透析。4例患者在ICU死亡(包括2例ICU再入院后死亡,即总死亡率为患者的4.8%)。CAR-T 治疗后一年,41/84例(48.9%)患者存活并处于完全缓解,14/84例(16.7%)存活但复发,29/84例(34.5%)已死亡。这些结局与从未入住ICU的患者相似。
Chimeric antigen receptor T-cell (CAR-T) therapy is increasingly used in patients with refractory haematological malignancies but can induce severe adverse events. We aimed to describe the clinical features and outcomes of patients admitted to the intensive care unit (ICU) after CAR-T therapy.
This retrospective observational cohort study included consecutive adults admitted to either of two French ICUs in 2018-2022 within 3 months after CAR-T therapy.
Among 238 patients given CAR-T therapy, 84 (35.3%) required ICU admission and were included in the study, a median of 5 [0-7] days after CAR-T infusion. Median SOFA and SAPSII scores were 3 [2-6] and 39 [30-48], respectively. Criteria for cytokine release syndrome were met in 80/84 (95.2%) patients, including 18/80 (22.5%) with grade 3-4 toxicity. Immune effector cell-associated neurotoxicity syndrome (ICANS) occurred in 46/84 (54.8%) patients, including 29/46 (63%) with grade 3-4 toxicity. Haemophagocytic lymphohistiocytosis was diagnosed in 15/84 (17.9%) patients. Tocilizumab was used in 73/84 (86.9%) patients, with a median of 2 [1-4] doses. Steroids were given to 55/84 (65.5%) patients, including 21/55 (38.2%) given high-dose pulse therapy. Overall, 23/84 (27.4%) patients had bacterial infections, 3/84 (3.6%) had fungal infections (1 invasive pulmonary aspergillosis and 2 Mucorales), and 2 (2.4%) had cytomegalovirus infection. Vasopressors were required in 23/84 (27.4%), invasive mechanical ventilation in 12/84 (14.3%), and dialysis in 4/84 (4.8%) patients. Four patients died in the ICU (including 2 after ICU readmission, i.e., overall mortality was 4.8% of patients). One year after CAR-T therapy, 41/84 (48.9%) patients were alive and in complete remission, 14/84 (16.7%) were alive and in relapse, and 29/84 (34.5%) had died. These outcomes were similar to those of patients never admitted to the ICU.
ICU admission is common after CAR-T therapy and is usually performed to manage specific toxicities. Our experience is encouraging, with low ICU mortality despite a high rate of grade 3-4 toxicities, and half of patients being alive and in complete remission at one year.
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