药物类别 | | | | | 全身皮质类固醇 | | | | 除甲状腺功能减退症和其他内分泌irAEs 可用激素补充治疗外的大多数免疫治疗相关irAEs 的主要治疗 | | | | | | | 局部皮质类固醇 | | | | | | | | | | | | | | | | | | | | | | | | | | 抗TNF-α 药物g-i | | | | 48~72 小时内对类固醇无反应的严重irAE 患者,免疫相关性结肠炎和炎性关节炎方面特别有效,避免用于免疫相关性肝炎患者 | | | 25mg 每周2次(间隔72~96 小时) 或 50mg每周1次 | | | | α-4β-7整联蛋 白抑制剂 | | | | | IL-6 抑制剂 | | | | | 含霉酚酸酯的药物j | | | | | 丙种球蛋白 k | | | | 在初始大剂量糖皮质激素疗效有限或无效后作为神经性irAEs 的二线或合并治疗 |
【注释】
a 对于特定的irAEs,如甲状腺功能减退症和其他内分泌irAEs,可用激素补充治疗,而不需要皮质类固醇治疗。 b 在免疫治疗过程中,允许使用灭活疫苗或死疫苗。由于活疫苗的使用尚不明确,因此不推荐在ICIs治疗期间使用。 c 皮质类固醇是大多数高级别irAEs的主要和初始治疗,目前尚无证据显示使用皮质类固醇治疗irAEs可降低 ICIs 的抗肿瘤疗效。 d 考虑到在预防情况下可能会降低ICIs 治疗的有效性,在单独使用ICIs 或联合没有既往输注反应的化疗药物时,不推荐常规使用皮质类固醇预处理。 e 对于神经系统、心脏或3、4 级irAEs,应给予较高剂量的类固醇(如甲泼尼龙或泼尼松1~2mg/(kg·d)。 f 对于在 48~72 小时内对类固醇无响应的严重irAEs 患者,可以考虑在早期(72小时内) 开始抗 TNF-α治疗(如英夫利西单抗5mg/kg)。可能需要追加给予抗TNF-α 治疗,并应在初次给予英夫利西单抗及其生物类似药后2 周和 6 周给药。 g 抗TNF-α 药物(如英夫利西单抗及其生物类似药) 在治疗免疫相关性结肠炎和炎性关节炎方面特别有效。 h 英夫利西单抗有乙型/ 丙型肝炎病毒和结核病再激活的风险,在使用前应检测乙肝/ 丙肝病毒、潜伏 / 活动性结核病。 i 抗 TNF-α 药物应避免用于免疫相关性肝炎患者,可使用维多利珠单抗来治疗免疫相关性结肠炎和伴随的肝炎。 j 含霉酚酸酯的药物包括霉酚酸(MPA) 或霉酚酸酯(MMF,MPA 的前药),现有证据支持该类药物用于治疗糖皮质激素无响应的严重 irAEs患者,包括累及肝、肾、胰腺和眼的 irAEs。 k 血浆置换和IVIG 的指征通常是在初始大剂量糖皮质激素疗效有限或无效后作为神经性irAEs 的二线或合并治疗。 l 作为后线免疫抑制治疗,但较少使用的药物包括利妥昔单抗、他克莫司、托珠单抗、环孢菌素、环磷酰胺、甲氨蝶呤和抗风湿药(如柳氮磺胺吡啶、来氟米特)。 m 接受免疫抑制剂治疗患者的支持治疗:长期全身性糖皮质激素需考虑预防高血糖、胃炎、机会性细菌或真菌感染,以及骨质疏松症。对于高血糖,推荐血糖监测及对症处理;对于胃炎,在类固醇治疗期间可给予H2受体阻滞剂或质子泵抑制剂;对于机会感染,考虑预防性抗菌和抗真菌药物。在接受相当于泼尼松≥20mg/d、≥ 4 周的患者中,应考虑预防肺囊虫肺炎(PJP),对于接受相当于泼尼松≥ 20mg/d、≥6 周的患者,可以使用磺胺甲唑预防肺孢子虫肺炎。考虑预防带状疱疹再激活。对于骨质疏松,考虑补充维生素D 和钙剂。 n 糖皮质激素逐渐减量:可能需要更长时间(4周以上,有时 6~8 周或更长) 以预防 irAEs 复发,特别是肺炎和肝炎。建议根据受累器官的缓解情况及炎性标志物的变化逐渐调整剂量。
参考指南: 中国临床肿瘤学会指南工作委员会.中国临床肿瘤学会 (CSCO) 免疫检查点抑制剂相关的毒性管理指南2023.人民卫生出版社.北京 2023
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