严重免疫相关性肝炎后使用免疫检查点抑制剂进行再治疗：一项前瞻性多中心研究的结果
Retreatment With Immune Checkpoint Inhibitors After a Severe Immune-Related Hepatitis: Results From a Prospective Multicenter Study.
作者信息
Riveiro-Barciela Mar, Barreira-Díaz Ana, Callejo-Pérez Ana, Muñoz-Couselo Eva, Díaz-Mejía Nely, Díaz-González Álvaro, Londoño María-Carlota, Salcedo Maria-Teresa, Buti María
机构信息
Liver Unit, Internal Medicine Department, Hospital Universitari Vall d'Hebron, Vall d'Hebron Barcelona Hospital Campus, Barcelona, Spain; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas, Instituto de Salud Carlos III, Madrid, Spain; Department of Medicine, Universitat Autònoma de Barcelona, Department of Medicine, Barcelona, Spain.
Liver Unit, Internal Medicine Department, Hospital Universitari Vall d'Hebron, Vall d'Hebron Barcelona Hospital Campus, Barcelona, Spain; Department of Medicine, Universitat Autònoma de Barcelona, Department of Medicine, Barcelona, Spain.
出版信息
Clin Gastroenterol Hepatol. 2023 Mar;21(3):732-740. doi: 10.1016/j.cgh.2022.03.050. Epub 2022 Apr 26.
BACKGROUND & AIMS: Liver injury related to immunotherapy is a relatively frequent immune-related adverse event that requires permanent discontinuation of immune checkpoint inhibitors (ICIs) in severe cases. We present the outcome of a cohort of patients who were retreated with immunotherapy after resolution of severe immune-related hepatitis.
METHODS
We performed a prospective, multicenter, noninterventional study that included all consecutive patients with cancer and previous grade 3 or 4 immune-related hepatitis who were retreated with ICIs in 3 academic hospitals.
RESULTS
Twenty-three patients who developed severe immune-related hepatitis were included: 20 of 23 (87.0%) received a single ICI and 3 of 23 (13.0%) received anti-programmed cell death protein-1 plus an anti-cytotoxic T-lymphocyte-associated antigen. The most frequent cancers were lung cell and urinary tract (7 and 6 cases, respectively). Immunotherapy was discontinued in all cases. Nineteen patients (82.6%) also received corticoids. Patients mainly were retreated with the same ICI (18 of 23; 78.3%) after a median time of 10 weeks (range, 1-54 wk) from the severe immune-related hepatitis. Fifteen patients (65.2%) did not have recurrence of the immune-related hepatitis after retreatment. Among the 8 (34.8%) subjects with recurrence, 5 of 8 were grade 3 and 3 of 8 were grade 4. Six (75%) had either an underlying autoimmune disease or antinuclear antibodies ≥1/80 (75% vs 26.7%; P = .037). None of the patients with previously grade 4 hepatitis had a recurrence, and those patients who had a recurrence tended to present with a better oncological prognosis. Overall, 19 (82.6%) subjects required permanent discontinuation of ICIs, with cancer progression the main reason for discontinuation (9 of 19; 47.8%).
CONCLUSIONS
Retreatment with ICIs is a feasible option after a severe immune-related hepatitis, even with the same ICIs, without recurrence of the liver injury retreatment in up to 65% of patients.
背景与目的
免疫治疗相关肝损伤是一种相对常见的免疫相关不良事件，严重时需永久停用免疫检查点抑制剂（ICI）。我们报告了一组在严重免疫相关肝炎缓解后接受免疫治疗再挑战患者的结局。
方法
我们进行了一项前瞻性、多中心、非干预性研究，纳入了3家学术医院中所有连续的曾患3级或4级免疫相关肝炎且接受ICI再挑战的癌症患者。
结果
纳入23例发生严重免疫相关肝炎的患者：23例中的20例（87.0%）接受了单一ICI，23例中的3例（13.0%）接受了抗程序性细胞死亡蛋白1加抗细胞毒性T淋巴细胞相关抗原治疗。最常见的癌症是肺癌和泌尿系统癌症（分别为7例和6例）。所有病例均停用了免疫治疗。19例患者（82.6%）还接受了皮质类固醇治疗。患者主要在距严重免疫相关肝炎中位时间10周（范围1 - 54周）后接受相同ICI再挑战（23例中的18例；78.3%）。15例患者（65.2%）再治疗后未出现免疫相关肝炎复发。在8例（34.8%）复发患者中，8例中的5例为3级，8例中的3例为4级。6例（75%）有潜在自身免疫性疾病或抗核抗体≥1/80（75%对26.7%；P = 0.037）。既往为4级肝炎的患者均无复发，且复发患者的肿瘤学预后往往较好。总体而言，19例（82.6%）患者需要永久停用ICI，癌症进展是停药的主要原因（19例中的9例；47.8%）。
结论
严重免疫相关肝炎后用ICI再治疗是一种可行的选择，即使使用相同的ICI，高达65%的患者再治疗时肝损伤未复发。
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