Kothapalli Anita, Khattak Muhammad A
Department of Medical Oncology, Fiona Stanley Hospital.
School of Medicine and Pharmacology, University of Western Australia.
Melanoma Res. 2018 Apr;28(2):155-158. doi: 10.1097/CMR.0000000000000434.
Anti-PD-1 monoclonal antibodies have shown durable long-term survival benefit in patients with metastatic melanoma. Limited evidence exists on the safety and efficacy of PD-1 inhibitors in patients with hepatitis B virus (HBV) and hepatitis C virus (HCV) infections as these patients have traditionally been excluded from clinical trials because of a theoretical risk of immune reconstitution inflammatory syndrome. We aim to determine the safety and efficacy of treatment with PD-1 inhibitors in seven patients with HBV/HCV infection and concurrent metastatic melanoma or non-small-cell lung cancer (NSCLC). We describe seven patients treated with PD-1 inhibitors nivolumab and pembrolizumab for either metastatic melanoma or metastatic NSCLC in the setting of chronic or past HBV/HCV infection. The safety and efficacy of treatment were analysed retrospectively by examining response to treatment, alanine transaminase (ALT) trends and viral load trends. One patient showed an increase in ALT of Common Terminology Criteria for Adverse Events (CTCAE) grade 2 severity that returned to the normal range following treatment of his HCV infection with ledipasvir 90 mg/sofosbuvir 400 mg. An additional four patients showed an increase in ALT of CTCAE grade 1 severity. The remaining two patients experienced no hepatic toxicity, with stable disease continuing after more than 24 cycles of nivolumab. Efficacy was similar to the data of published trials. Our results indicate that patients with metastatic melanoma and NSCLC can be treated safely with PD-1 inhibitors in the context of HBV/HCV infection. However, we recommend that those with active viral hepatitis be monitored closely in consultation with a hepatologist and treated with antiviral therapy if indicated.
抗程序性死亡蛋白1（PD-1）单克隆抗体已在转移性黑色素瘤患者中显示出持久的长期生存获益。关于PD-1抑制剂在乙型肝炎病毒（HBV）和丙型肝炎病毒（HCV）感染患者中的安全性和疗效，现有证据有限，因为这些患者传统上因存在免疫重建炎症综合征的理论风险而被排除在临床试验之外。我们旨在确定PD-1抑制剂治疗7例HBV/HCV感染合并转移性黑色素瘤或非小细胞肺癌（NSCLC）患者的安全性和疗效。我们描述了7例在慢性或既往HBV/HCV感染背景下接受PD-1抑制剂纳武单抗和派姆单抗治疗转移性黑色素瘤或转移性NSCLC的患者。通过检查治疗反应、丙氨酸转氨酶（ALT）趋势和病毒载量趋势，对治疗的安全性和疗效进行回顾性分析。1例患者出现不良事件通用术语标准（CTCAE）2级严重程度的ALT升高，在用90毫克来迪派韦/400毫克索磷布韦治疗其HCV感染后恢复至正常范围。另外4例患者出现CTCAE 1级严重程度的ALT升高。其余2例患者未出现肝毒性，在接受超过24个周期的纳武单抗治疗后疾病持续稳定。疗效与已发表试验的数据相似。我们的结果表明，转移性黑色素瘤和NSCLC患者在HBV/HCV感染的情况下可以安全地接受PD-1抑制剂治疗。然而，我们建议对活动性病毒性肝炎患者与肝病专家协商密切监测，如有指征则进行抗病毒治疗。
