Peaytt Rachel, Parsons Laura Beth, Siler Darby, Matthews Rachel, Li Belinda, Bell David, Bachier Carlos, Pantin Jeremy, Berdeja Jesus, Flinn Ian, Donnellan William, Battiwalla Minoo
23769TriStar Centennial Medical Center, Nashville, TN, USA.
14360Emory Healthcare, Atlanta, GA, USA.
J Oncol Pharm Pract. 2023 Jan;29(1):45-51. doi: 10.1177/10781552211052635. Epub 2021 Nov 24.
Cytokine release syndrome is a life-threatening hyper-inflammatory state induced by immune effector cell therapy. Anti-interleukin 6-(IL-6) therapy, such as tocilizumab, is the standard treatment for cytokine release syndrome since it reverses symptoms without compromising immune effector cell therapy efficacy. Glucocorticoids are reserved for refractory or severe cytokine release syndrome due to concern for attenuating antitumor activity. Optimizing the timing of tocilizumab could avoid glucocorticoid use and improve outcomes. This study assesses tocilizumab timing on patient outcomes and healthcare resource utilization.
This is a retrospective single-institution analysis of 28 patients who received tocilizumab for cytokine release syndrome secondary to immune effector cell therapy. Patients were categorized into two groups: Early Tocilizumab (within 24 h) or Late Tocilizumab groups (more than 24 h) from fever onset. The composite primary endpoint was glucocorticoid use, intensive care unit admission, or inpatient mortality. Secondary outcomes include comparing the various presentations of cytokine release syndrome, need for vasopressors, length of stay, rates of neurotoxicity, and C-reactive protein and ferritin trends.
The Early Tocilizumab group presented with more rapid fever onset (35 vs.113 h, = 0.017) and higher maximum cytokine release syndrome grade (Median, Grade 2 vs. Grade 1, = 0.025). Additionally, the Early Tocilizumab group required more doses of tocilizumab (Median, 2 vs. 1, = 0.037). Despite the difference in cytokine release syndrome presentation, the primary composite endpoint was not statistically different between groups.
Earlier onset of fever appears to be associated with more severe, progressive cytokine release syndrome requiring multiple doses of anti-interleukin-6 therapy. Prompt and aggressive tocilizumab treatment could be protective against the negative consequences of cytokine release syndrome.
细胞因子释放综合征是一种由免疫效应细胞疗法诱导的危及生命的高炎症状态。抗白细胞介素6（IL-6）疗法，如托珠单抗，是细胞因子释放综合征的标准治疗方法，因为它能逆转症状而不影响免疫效应细胞疗法的疗效。由于担心糖皮质激素会减弱抗肿瘤活性，因此仅用于难治性或严重的细胞因子释放综合征。优化托珠单抗的使用时机可以避免使用糖皮质激素并改善治疗结果。本研究评估了托珠单抗使用时机对患者治疗结果和医疗资源利用的影响。
这是一项对28例因免疫效应细胞疗法继发细胞因子释放综合征而接受托珠单抗治疗的患者进行的回顾性单机构分析。从发热开始，将患者分为两组：早期托珠单抗组（24小时内）或晚期托珠单抗组（超过24小时）。复合主要终点是糖皮质激素的使用、重症监护病房入院或住院死亡率。次要结果包括比较细胞因子释放综合征的各种表现、血管升压药的需求、住院时间、神经毒性发生率以及C反应蛋白和铁蛋白的变化趋势。
早期托珠单抗组发热开始更快（35小时对113小时，P = 0.017），细胞因子释放综合征最高分级更高（中位数，2级对1级，P = 0.025）。此外，早期托珠单抗组需要更多剂量的托珠单抗（中位数，2剂对1剂，P = 0.037）。尽管细胞因子释放综合征的表现存在差异，但两组的主要复合终点在统计学上没有差异。
发热较早出现似乎与更严重、进展性的细胞因子释放综合征相关，需要多剂量的抗白细胞介素-6治疗。及时且积极的托珠单抗治疗可能对细胞因子释放综合征的不良后果具有保护作用。
