School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran.
Neurogenic Inflammation Research Center, Mashhad University of Medical Sciences, Mashhad, Iran; Biotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran.
Int Immunopharmacol. 2019 Apr;69:150-158. doi: 10.1016/j.intimp.2019.01.035. Epub 2019 Jan 31.
Malignancy is a significant cause of mortality after organ transplantation. There is an increased rate of malignancy following heart transplantation (HTx) compared to the general population and other organ transplant recipients. Post-HTx patients with a history of malignancy are also at a higher risk of developing new malignancies or exacerbation of their existing malignancies. Mammalian target of Rapamycin inhibitors (mTORIs) are newly introduced immunosuppressive drugs with a unique mechanism of action. By changing the immunosuppressive regimen from classic drugs, especially calcineurin inhibitors (CNIs) to mTORIs, the rate of developing de novo malignancies and the relapse of former malignancies is significantly reduced. However, issues like allograft function, total surveillance of patients, and post-transplantation complications should be considered during the conversion of drug regimens utilizing CNIs to drug regimens employing mTORIs. We reviewed different post-heart transplant maintenance immunosuppressive regimens and their effect on post-HTx malignancies with a focus on mTORIs, compared safety against effectiveness, and gathered conclusions based on our review of the literature, which may lead clinicians to make a better evidence-based decision regarding post-HTx maintenance immunosuppressive drug regimens. Overall, CNI to mTORI conversion in post-HTx maintenance immunosuppressive drug regimens was associated with a reduced rate of developing malignancy in post-HTx patients. Furthermore, nephrotoxicity decreased significantly while using mTORIs in combination with lower doses of CNIs and the rejection rate was equivalent to CNI-only regimens. In conclusion, mTORI-based maintenance immunosuppressive drug regimens seem to be safe and beneficial when considering efficacy vs. adverse effects, and all-cause mortality rates are significantly lower in patients switched to mTORIs when compared to CNI recipients.
恶性肿瘤是器官移植后死亡的重要原因。与一般人群和其他器官移植受者相比，心脏移植（HTx）后恶性肿瘤的发生率增加。有恶性肿瘤病史的 HTx 后患者发生新的恶性肿瘤或现有恶性肿瘤恶化的风险也更高。雷帕霉素靶蛋白抑制剂（mTORIs）是一种新引入的具有独特作用机制的免疫抑制剂。通过将免疫抑制方案从经典药物（特别是钙调磷酸酶抑制剂（CNIs））改变为 mTORIs，可以显著降低新发恶性肿瘤的发生率和先前恶性肿瘤的复发率。然而，在将 CNI 方案转换为 mTORI 方案时，应考虑移植物功能、患者的全面监测和移植后并发症等问题。我们回顾了不同的心脏移植后维持性免疫抑制方案及其对 HTx 后恶性肿瘤的影响，重点关注 mTORIs，比较了安全性与有效性，并根据文献复习得出结论，这可能使临床医生在 HTx 后维持性免疫抑制药物方案方面做出更好的基于证据的决策。总体而言，在 HTx 后维持性免疫抑制药物方案中，从 CNI 转换为 mTORI 与降低 HTx 后患者发生恶性肿瘤的风险相关。此外，联合使用 mTORIs 和较低剂量的 CNI 可显著降低肾毒性，而排斥反应率与 CNI 单药方案相当。总之，从疗效与不良反应的角度来看，mTORI 为基础的维持性免疫抑制药物方案似乎是安全且有益的，与 CNI 受者相比，转换为 mTORI 的患者的全因死亡率显著降低。
