Piazza Lavinia, Carollo Anna, Di Martino Enrica, Novara Maria Eugenia, Cutaia Sofia, Provenzani Alessio, Rizzo Sergio
Università degli Studi di Milano, Department of Pharmacy, Italy.
Clinical Pharmacy Service, Mediterranean Institute for Transplantation and Advanced Specialized Therapies (ISMETT), Palermo, Italy.
Crit Rev Oncol Hematol. 2025 Feb;206:104587. doi: 10.1016/j.critrevonc.2024.104587. Epub 2024 Dec 10.
The aim of this systematic review was to assess the risk of cardiac toxicity in patients undergoing approved PD-1 (nivolumab, pembrolizumab, cemiplimab, dostarlimab), PD-L1 (atezolizumab, avelumab, durvalumab), and CTLA-4 (ipilimumab) inhibitors.
Among a total of 2272 articles, 11 phase II and III clinical trials included: 5463 patients and 175 cardiac adverse events. The most common cardiac disorder was atrial fibrillation (12 %), while cardiac arrest and cardiac failure (6 %) led to death in three cases. Overall, ICI treatment increased the risk of cardiotoxicity compared with control groups (RR=1.62, 95 %-CI= 1.18-2.24, p-value=0.0033; OR=1.71, 95 %-CI= 1.20-2.42, p-value=0.0027).
This study proved that the recognition of frequency and severity of all grade cardiotoxicity associated with ICIs is still underestimated. Thus, a systematic cardiological screening becomes necessary, in order to intercept the potential cardiological complications beforehand and optimize the outcomes of the respective treatment with PD-1, PD-L1 and CTLA-4 inhibitors.
本系统评价的目的是评估接受已获批的程序性死亡受体1（PD-1）抑制剂（纳武利尤单抗、帕博利珠单抗、西米普利单抗、多斯塔利单抗）、程序性死亡受体配体1（PD-L1）抑制剂（阿替利珠单抗、阿维鲁单抗、度伐利尤单抗）和细胞毒性T淋巴细胞相关抗原4（CTLA-4）抑制剂（伊匹木单抗）治疗的患者发生心脏毒性的风险。
在总共2272篇文章中，纳入了11项II期和III期临床试验，涉及5463例患者和175例心脏不良事件。最常见的心脏疾病是心房颤动（12%），而心脏骤停和心力衰竭（6%）导致3例死亡。总体而言，与对照组相比，免疫检查点抑制剂（ICI）治疗增加了心脏毒性风险（风险比[RR]=1.62，95%置信区间[CI]=1.18-2.24，P值=0.0033；比值比[OR]=1.71，95%CI=1.20-2.42，P值=0.0027）。
本研究证明，与ICI相关的所有级别心脏毒性的发生频率和严重程度仍被低估。因此，有必要进行系统的心脏筛查，以便预先拦截潜在的心脏并发症，并优化使用PD-1、PD-L1和CTLA-4抑制剂的相应治疗效果。
