Universidade Federal de São Paulo, Hospital do Rim, Divisão de Nefrologia, São Paulo, SP, Brazil.
Universidade Federal de São Paulo, Divisão de Dermatologia, São Paulo, SP, Brazil.
J Bras Nefrol. 2023 Oct-Dec;45(4):480-487. doi: 10.1590/2175-8239-JBN-2023-0013en.
Previous research demonstrated benefits of late conversion to mTOR inhibitors against cutaneous squamous cell carcinomas (cSCC) in kidney transplant recipients (KTR), despite of poor tolerability. This study investigated whether stepwise conversion to sirolimus monotherapy without an attack dose modified the course of disease with improved tolerability.
This prospective exploratory study included non-sensitized KTR with more than 12-months post-transplant, on continuous use of calcineurin inhibitors (CNI)-based therapy, and with poor-prognosis cSCC lesions. Incidence densities of high-risk cSCC over 3-years after conversion to sirolimus-monotherapy were compared to a non-randomized group with high-risk cSCC but unsuitable/not willing for conversion.
Forty-four patients were included (83% male, mean age 60 ± 9.7years, 62% with skin type II, mean time after transplantation 9 ± 5.7years). There were 25 patients converted to SRL and 19 individuals kept on CNI. There was a tendency of decreasing density of incidence of all cSCC in the SRL group and increasing in the CNI group (1.49 to 1.00 lesions/patient-year and 1.74 to 2.08 lesions/patient-year, p = 0.141). The density incidence of moderately differentiated decreased significantly in the SRL group while increasing significantly in the CNI group (0.31 to 0.11 lesions/patient-year and 0.25 to 0.62 lesions/patient-year, p = 0.001). In the SRL group, there were no sirolimus discontinuations, no acute rejection episodes, and no de novo DSA formation. Renal function remained stable.
This study suggests that sirolimus monotherapy may be useful as adjuvant therapy of high-risk cSCC in kidney transplant recipients. The conversion strategy used was well tolerated and safe regarding key mid-term transplant outcomes.
先前的研究表明，尽管 mTOR 抑制剂的耐受性较差，但在肾移植受者（KTR）中晚期转换为 mTOR 抑制剂对皮肤鳞状细胞癌（cSCC）有获益。本研究旨在探究是否逐步转换为无需起始剂量的西罗莫司单药治疗，能否在改善耐受性的同时改变疾病进程。
本前瞻性探索性研究纳入了移植后超过 12 个月、持续使用钙调磷酸酶抑制剂（CNI）为基础的治疗方案且患有预后不良的 cSCC 病变的非致敏 KTR。将转换为西罗莫司单药治疗后 3 年内高危 cSCC 的发生率密度与未随机分组的、患有高危 cSCC 但不适合/不愿意转换的患者进行比较。
共纳入 44 例患者（83%为男性，平均年龄 60 ± 9.7 岁，62%为皮肤类型 II，移植后时间平均为 9 ± 5.7 年）。25 例患者转换为 SRL，19 例患者继续使用 CNI。SRL 组 cSCC 的总发生率和中分化 cSCC 的发生率均呈下降趋势，而 CNI 组的发生率则呈上升趋势（1.49 至 1.00 例/患者-年和 1.74 至 2.08 例/患者-年，p = 0.141）。SRL 组中分化程度的 cSCC 发生率显著下降，而 CNI 组则显著上升（0.31 至 0.11 例/患者-年和 0.25 至 0.62 例/患者-年，p = 0.001）。在 SRL 组中，没有患者停止使用西罗莫司，没有发生急性排斥反应，也没有新形成的 de novo DSA。肾功能保持稳定。
本研究表明，西罗莫司单药治疗可能有助于肾移植受者高危 cSCC 的辅助治疗。所使用的转换策略在关键的中期移植结果方面具有良好的耐受性和安全性。
