帕博利珠单抗致严重免疫性肝损伤再挑战1例分析

A case of severe immune liver injury caused by pembrolizumab and rechallenge

1例老年女性黑色素瘤患者,接受帕博利珠单抗和阿昔替尼治疗后出现严重肝损伤,给予糖皮质激素治疗好转。通过用药分析及不良反应量表评估,考虑严重肝损伤与免疫检查点抑制剂帕博利珠单抗的使用关系更大。综合分析肝损伤与免疫治疗的关系以及患者免疫治疗获益与风险,在停用帕博利珠单抗40 d后再挑战免疫治疗。帕博利珠单抗致免疫相关肝毒性后重启治疗存在肝毒性复发风险,结合文献发现免疫再挑战致严重肝毒性的发生率不高,安全性整体可控。帕博利珠单抗为患者带来治疗获益,截至5周期用药后未再发生严重肝损伤。本病例可为发生免疫相关肝毒性后再挑战免疫治疗提供参考。

An elderly female melanoma patient who experienced severe liver injury after treatment with pembrolizumab and axitinib,which improved with glucocorticoid therapy.Through medication analysis and adverse reaction scale evaluated,it was considered that severe liver injury was more closely related to the immune checkpoint inhibitor,pembrolizumab.After a comprehensive analysis of the relationship between liver injury and immunotherapy,as well as the benefits and risks of immunotherapy for patients,immunotherapy was rechallenged 40 days after discontinuation of pembrolizumab.Restarting treatment with pembrolizumab after immune-mediated hepatitis poses a risk of recurrence of hepatotoxicity.After reviewing related literature,it had been found that the incidence of severe hepatotoxicity caused by rechallenging treatment was low,and the overall safety was controllable.Pembrolizumab had brought therapeutic benefits to patients,with no further immune-mediated liver injury of 5 cycles medication.This case can provide a reference for rechallenging immunotherapy after immune-mediated hepatitis.