FDA Approval Summary: Tocilizumab for Treatment of Chimeric Antigen Receptor T Cell-Induced Severe or Life-Threatening Cytokine Release Syndrome.
FDA Approval Summary: Tocilizumab for Treatment of Chimeric Antigen Receptor T Cell-Induced Severe or Life-Threatening Cytokine Release Syndrome.
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DOI：
10.1634/theoncologist.2018-0028
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发表时间：
2018-08
期刊：
影响因子：
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通讯作者：
Pazdur R
中科院分区：
文献类型：
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作者：
Le RQ;Li L;Yuan W;Shord SS;Nie L;Habtemariam BA;Przepiorka D;Farrell AT;Pazdur R
本文总结了支持tocilizumab获批用于治疗重度或危及生命的CAR T细胞诱导的细胞因子释放综合征的关键审查结果。2017年8月30日，美国食品和药物管理局批准Actemra（托珠单抗，Genentech，Inc.，South San弗朗西斯科，CA），用于治疗成人和2岁及以上儿童患者的重度或危及生命的嵌合抗原受体（CAR）T细胞诱导的细胞因子释放综合征（CRS）。该批准是基于对前瞻性临床试验中使用CTL 019和KTE-C19治疗后发生CRS的患者数据的回顾性分析。可评价的患者接受了静脉内托珠单抗8 mg/kg（<30 kg的患者为12 mg/kg）治疗重度或危及生命的CRS;仅CRS首次发作被纳入分析。CTL 019队列的疗效人群包括24例男性和21例女性患者（共45例患者），中位年龄12岁。从CRS开始至托珠单抗首次给药的中位时间为4天（范围，0-18天）。如果CRS在托珠单抗首次给药后14天内消退，如果需要的托珠单抗剂量不超过2次，如果未使用托珠单抗和皮质类固醇以外的药物进行治疗，则认为患者是应答者。31例患者（69%; 95%置信区间，53%-82%）达到了规定的缓解。在一个由15名KTE-C19诱导的CRS患者组成的独立队列中，53%的患者有反应。需要进一步的研究来确定托珠单抗的最佳剂量，并确认其用于治疗CAR T细胞诱导的CRS患者的安全性。严重或危及生命的嵌合抗原受体（CAR）T细胞诱导的细胞因子释放综合征（CRS）需要紧急治疗，以防止致命性结局。在两个独立的队列中，大多数重度或危及生命的CAR T细胞诱导的CRS患者除了高级支持治疗外，还对一剂或两剂托珠单抗治疗有反应。需要更多的研究来确定托珠单抗治疗CAR T细胞诱导的CRS的最佳剂量和时间表。
This article summarizes key review findings that supported the approval of tocilizumab for treatment of severe or life‐threatening CAR T cell‐induced cytokine release syndrome. On August 30, 2017, the U.S. Food and Drug Administration approved Actemra (tocilizumab, Genentech, Inc., South San Francisco, CA) for the treatment of severe or life‐threatening chimeric antigen receptor (CAR) T cell‐induced cytokine release syndrome (CRS) in adults and in pediatric patients 2 years of age and older. The approval was based on a retrospective analysis of data for patients who developed CRS after treatment with CTL019 and KTE‐C19 on prospective clinical trials. Evaluable patients had been treated with intravenous tocilizumab 8 mg/kg (12 mg/kg for patients <30 kg) for severe or life‐threatening CRS; only the first episode of CRS was included in the analysis. The efficacy population for the CTL019 cohort included 24 male and 21 female patients (total 45 patients) of median age 12 years. The median time from the start of CRS to the first dose of tocilizumab was 4 days (range, 0–18 days). Patients were considered responders if CRS resolved within 14 days of the first dose of tocilizumab, if no more than 2 doses of tocilizumab were needed, and if no drugs other than tocilizumab and corticosteroids were used for treatment. Thirty‐one patients (69%; 95% confidence interval, 53%–82%) achieved a response as defined. In an independent cohort of 15 patients with KTE‐C19‐induced CRS, 53% responded. Further study is needed to determine the optimal dose of tocilizumab and to confirm the safety of its use for treatment of patients with CAR T cell‐induced CRS. Severe or life‐threatening chimeric antigen receptor (CAR) T cell‐induced cytokine release syndrome (CRS) requires urgent treatment to prevent fatal outcomes. In two independent cohorts, the majority of patients with severe or life‐threatening CAR T cell‐induced CRS responded to treatment with one or two doses of tocilizumab in addition to advanced supportive care. More research is needed to determine the optimal dose and schedule of tocilizumab for treatment of CAR T cell‐induced CRS.