托法替布治疗癌症免疫治疗相关免疫不良事件的多中心观察性研究。
Tofacitinib for the treatment of immune-related adverse events in cancer immunotherapy: a multi-center observational study.
机构信息
Department of Medical Oncology, Zhongshan Hospital, Fudan University, 180 Fenglin Road, Shanghai, 200032, China.
Cancer Center, Zhongshan Hospital, 180 Fenglin Road, Shanghai, 200032, China.
出版信息
J Transl Med. 2024 Aug 29;22(1):803. doi: 10.1186/s12967-024-05617-6.
BACKGROUND
Treatment strategy against immune-related adverse events (irAEs) induced by immune checkpoint inhibitors (ICIs) frequently requires other immunosuppressive agents. Tofacitinib is a rapidly acting JAK-STAT inhibitor with proven efficacy in multiple autoimmune diseases. We aimed to evaluate the efficacy and safety of tofacitinib in the management of irAEs in cancer patients.
METHODS
Cancer patients who received ICIs and were treated with tofacitinib for the management of irAEs at 6 institutions were retrospectively included in this study. Demographic and clinical characteristics were obtained from electronic medical records. Longitudinal assessment of cardiac troponin T (cTnT) with clinical assessment was utilized to evaluate the benefit of tofacitinib treatment in patients with ICI myocarditis. Overall survival (OS) was also assessed.
RESULTS
Fifty-three patients were included in this study. The median time from irAE onset to tofacitinib therapy was 17 (range, 2-186) days and the median duration of tofacitinib treatment was 52.5 (range, 3-277) days. Enrolled patients were subdivided into 3 groups based on clinical severity and steroid responsiveness including 11 life-threatening cases, 30 steroid-resistant cases, and 12 cases with steroid taper failure. Clinical remission rate in each group was 54.5%, 96.7%, and 100%, respectively (P < 0.01). Tofacitinib was well-tolerated with 4 patients (7.5%) developing infectious events. From the ICI initiation, the overall median OS was 16.1 (95% CI 7.8-26.9) months.
CONCLUSION
Tofacitinib showed promising clinical efficacy in patients experiencing irAEs, particularly in patients who failed to respond to steroids or experienced relapse during steroid tapering. Moreover, and most importantly, tofacitinib exhibited a favorable safety profile in cancer patients developing irAEs in terms of both toxicity and anti-tumor activity. Future prospective studies are warranted.
背景
针对免疫检查点抑制剂（ICI）引起的免疫相关不良反应（irAE）的治疗策略通常需要其他免疫抑制剂。托法替布是一种快速作用的 JAK-STAT 抑制剂，已在多种自身免疫性疾病中证明有效。我们旨在评估托法替布在癌症患者 irAE 管理中的疗效和安全性。
方法
本研究回顾性纳入了在 6 家机构接受 ICI 治疗并接受托法替布治疗 irAE 的癌症患者。从电子病历中获取人口统计学和临床特征。通过临床评估对心肌肌钙蛋白 T（cTnT）进行纵向评估，以评估托法替布治疗 ICI 心肌炎患者的获益。还评估了总生存期（OS）。
结果
本研究纳入了 53 例患者。irAE 发病至托法替布治疗的中位时间为 17（范围，2-186）天，托法替布治疗的中位时间为 52.5（范围，3-277）天。根据临床严重程度和类固醇反应性将入组患者分为 3 组，包括 11 例危及生命的病例、30 例类固醇耐药的病例和 12 例类固醇减量失败的病例。每组的临床缓解率分别为 54.5%、96.7%和 100%（P<0.01）。托法替布耐受性良好，有 4 例（7.5%）发生感染事件。从 ICI 开始，总体中位 OS 为 16.1（95%CI 7.8-26.9）个月。
结论
托法替布在 irAE 患者中显示出有希望的临床疗效，特别是在对类固醇无反应或在类固醇减量期间复发的患者中。此外，最重要的是，托法替布在发生 irAE 的癌症患者中具有良好的安全性，无论在毒性还是抗肿瘤活性方面。需要进行前瞻性研究。
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