Grant Michael J, DeVito Nicholas, Salama April K S
Department of Medicine, Duke University Medical Center, Durham, NC 27710, USA.
Duke Cancer Institute, Duke University Medical Center, Durham, NC, USA.
Melanoma Manag. 2018 Oct 26;5(4):MMT10. doi: 10.2217/mmt-2018-0004. eCollection 2018 Dec.
Due to the unique side-effect profile of immune checkpoint inhibitors (ICIs), groups of patients deemed to be at high risk of complications were excluded from trials that proved the efficacy and safety of these agents in patients with various malignancies. Among these excluded patients were those with prior solid organ transplantation, chronic viral infections and pre-existing autoimmune diseases including paraneoplastic syndromes. We present follow-up on a patient from a previously published case report with an orthotopic heart transplantation who was treated with both cytotoxic T-lymphocyte antigen 4 and PD-1 inhibition safely, without organ rejection. Additionally, we describe the case of a patient with a cardiac allograft who also did not experience organ rejection after treatment with pembrolizumab. Through smaller trials, retrospective analyses, case series and individual case reports, we are accumulating initial data on how these agents are tolerated by the aforementioned groups. Our survey of the literature has found more evidence of organ transplant rejection in patients treated with PD-1 inhibitors than those treated with inhibitors of cytotoxic T-lymphocyte antigen 4. Patients with chronic viral infections, especially hepatitis C, seem to have little to no risk of treatment-related increase in serum RNA levels. The literature contains few documented cases of devastating exacerbations of pre-existing autoimmune disease during treatment with ICIs, and flares seem to be easily controlled by immunosuppression in the vast majority of cases. Last, several cases allude to a promising role for disease-specific antibodies and other serum biomarkers in identifying patients at high risk of developing certain immune-related adverse events, detecting subclinical immune-related adverse event onset, and monitoring treatment response to immunosuppressive therapy in patients treated with ICIs. Though these excluded populations have not been well studied in randomized placebo-controlled trials, we may be able to learn and derive hypotheses from the existing observational data in the literature.
由于免疫检查点抑制剂（ICI）具有独特的副作用特征，在证明这些药物对各种恶性肿瘤患者的疗效和安全性的试验中，被认为并发症风险高的患者群体被排除在外。这些被排除的患者包括既往有实体器官移植、慢性病毒感染以及包括副肿瘤综合征在内的自身免疫性疾病患者。我们对之前发表的一例原位心脏移植患者进行了随访，该患者接受细胞毒性T淋巴细胞抗原4和PD-1抑制治疗后安全无器官排斥反应。此外，我们还描述了一例心脏同种异体移植患者在接受派姆单抗治疗后也未发生器官排斥反应的病例。通过小型试验、回顾性分析、病例系列和个案报告，我们正在积累关于上述群体如何耐受这些药物的初步数据。我们对文献的调查发现，与接受细胞毒性T淋巴细胞抗原4抑制剂治疗的患者相比，接受PD-1抑制剂治疗的患者发生器官移植排斥反应的证据更多。慢性病毒感染患者，尤其是丙型肝炎患者，似乎几乎没有或没有治疗相关血清RNA水平升高的风险。文献中记录的ICI治疗期间既往自身免疫性疾病严重恶化的病例很少，而且在绝大多数情况下，病情发作似乎很容易通过免疫抑制得到控制。最后，有几例病例暗示疾病特异性抗体和其他血清生物标志物在识别有发生某些免疫相关不良事件高风险的患者、检测亚临床免疫相关不良事件发作以及监测接受ICI治疗患者的免疫抑制治疗反应方面具有潜在作用。尽管这些被排除的人群在随机安慰剂对照试验中尚未得到充分研究，但我们或许能够从文献中现有的观察数据中学习并得出假设。
