6例免疫检查点抑制剂挽救性治疗肝癌肝移植术后肿瘤复发的初步评价

Preliminary evaluation of immune checkpoint inhibitors as a salvage treatment of tumor recurrence after liver transplantation for hepatocellular carcinoma

目的探讨免疫检查点抑制剂(immune checkpoint inhibitors,ICI)治疗对于肝癌肝移植术后肿瘤复发受者的安全性和有效性。方法对浙江树人大学树兰国际医学院附属树兰(杭州)医院2015年9月至2018年6月收治的使用ICI治疗的6例肝癌肝移植术后肿瘤复发受者的临床资料进行回顾性研究。分析评估PD-1/PD-L1抑制剂治疗后,移植物排斥反应的发生情况及总体有效率、无进展生存期和总生存期等临床结果。结果6例受者中,使用纳武利尤单抗(Nivolumab)者4例,度伐利尤单抗(Durvalumab)者2例;中位疗程为8.3个(2~31)个周期。疾病稳定3例,疾病进展3例。疾病稳定3例的无进展生存期分别为1.5、16.2、18.0个月,复发后中位生存期为19.75个(10.8~37.8)个月。出现急性排斥反应1例,排斥反应发生的时间为应用PD-1抑制剂后第28天,受者接受了大剂量糖皮质激素与兔抗人胸腺细胞免疫球蛋白冲击治疗,但最终还是因急性排斥反应导致的肝功能衰竭而死亡。结论ICI可以作为肝癌肝移植术后肿瘤复发的挽救性治疗手段之一,但也可能诱发严重的急性排斥反应,应在密切监测肝功能的情况下谨慎使用。

Objective To explore the safety and efficacy of immune checkpoint inhibitors(ICI)for patients with tumor recurrence after liver transplantation(LT).Methods A single-center retrospective study was conducted for 6 recipients of tumor recurrence after LT on a therapy of ICI admitted into Shulan(Hang Zhou)Hospital from September 2015 to June 2018.The authors examined the occurrences of graft rejection and clinical outcomes of overall response rate,progression-free survival and overall survival after dosing of PD-1/PD-L1 inhibitors.Results Six patients enrolled with tumor recurrence on a therapy of ICI undergoing LT due to hepatocellular carcinoma(HCC).Nivolumab(n=4)and duvalizumab(n=2)were administrated.The median session of treatment was 8.3(2-31)cycles.The disease outcomes were stable(3/6,50%)and progressive(3/6,50%),The progression-free survival time of 3 disease-controlled patients was 1.5,16.2 and 18 months and the median survival time after recurrence was 19.75(10.8-37.8)months.Rejection occurred in 1 patients(1/6,16.7%)and the occurring time of rejection was 28 days after PD-1 inhibitor dosing.After acute rejection,high-dose corticosteroids and immunoglobulin were ineffective and the patient died from acute rejection related liver failure.Conclusions ICI may be employed as a salvage treatment for tumor recurrence after LT for HCC.Due to a possibility of severe acute rejection,usage should be cautious under close monitoring of liver function.