Division of Nephrology and Hypertension, Mayo Clinic, Rochester, MN, United States.
Department of Surgery, Mayo Clinic, Rochester, MN, United States.
Transpl Int. 2024 Oct 16;37:13322. doi: 10.3389/ti.2024.13322. eCollection 2024.
Immune checkpoint inhibitor (ICI) therapy has enabled a paradigm shift in Oncology, with the treatment of metastatic cancer in certain tumor types becoming akin to the treatment of chronic disease. Kidney transplant recipients (KTR) are at increased risk of developing cancer compared to the general population. Historically, KTR were excluded from ICI clinical trials due to concern for allograft rejection and decreased anti-tumor efficacy. While early post-marketing data revealed an allograft rejection risk of 40%-50%, 2 recent small prospective trials have demonstrated lower rates of rejection of 0%-12%, suggesting that maintenance immunosuppression modification prior to ICI start modulates rejection risk. Moreover, objective response rates induced by ICI for the treatment of advanced or metastatic skin cancer, the most common malignancy in KTR, have been comparable to those achieved by immune intact patients. Non-invasive biomarkers may have a role in risk-stratifying patients before starting ICI, and monitoring for rejection, though allograft biopsy is required to confirm diagnosis. This clinically focused review summarizes current knowledge on complications of ICI use in KTR, including their mechanism, risk mitigation strategies, non-invasive biomarker use, approaches to treatment of rejection, and suggestions for future directions in research.
免疫检查点抑制剂 (ICI) 治疗在肿瘤学领域引发了范式转变,某些肿瘤类型的转移性癌症的治疗方法类似于慢性疾病的治疗方法。与普通人群相比,肾移植受者 (KTR) 患癌症的风险增加。由于担心移植物排斥和抗肿瘤疗效降低,历史上 KTR 被排除在 ICI 临床试验之外。虽然早期上市后数据显示移植物排斥风险为 40%-50%,但最近的两项小型前瞻性试验显示排斥率较低,为 0%-12%,表明在开始 ICI 之前进行维持免疫抑制药物的调整可降低排斥风险。此外,ICI 治疗 KTR 中最常见的皮肤癌(晚期或转移性皮肤癌)引起的客观缓解率与免疫功能正常患者相当。非侵入性生物标志物可能在开始使用 ICI 之前对患者进行风险分层以及监测排斥反应方面发挥作用,尽管需要进行移植物活检以确认诊断。本临床重点综述总结了 KTR 使用 ICI 后出现的并发症的现有知识,包括其发病机制、降低风险策略、非侵入性生物标志物的使用、排斥反应的治疗方法以及对未来研究方向的建议。