Rahman Afsana, Lee Changhee, Rahman Salwa, Baranowska Julia, Moeller Cathrine M, Valledor Andrea Fernandez, Rubenstein Gal, Oren Daniel, Alnatour Adel T, Labarre Brian, Taek Kyung, Bae David, Raikhelkar Jayant, Lotan Dor, Defilippis Ersilia M, Yunis Adil A, Fried Justin, Latif Farhana, Yuzefpolskaya Melana, Colombo Paolo C, Lin Edward, Majure David T, Clerkin Kevin J, Choe Jason, Sayer Gabriel, Uriel Nir
Columbia University Irving Medical Center, New York, New York.
NewYork-Presbyterian Hospital, New York, New York.
J Card Fail. 2025 Jun 23. doi: 10.1016/j.cardfail.2025.05.017.
Cytomegalovirus (CMV) infection post-heart transplantation (HT) is associated with worse outcomes. Antiviral prophylaxis for at-risk patients is the standard of care. Valganciclovir, the most commonly used antiviral drug, is associated with significant adverse events, particularly leukopenia. Letermovir is a CMV-specific antiviral drug with a favorable side effect profile but its efficacy in HT recipients is unclear. This study aims to assess the safety and efficacy of letermovir for CMV prophylaxis in HT recipients.
This single-center retrospective analysis included HT recipients at our center from January 2020 to September 2023. Patients who were switched to letermovir for CMV prophylaxis for leukopenia/neutropenia on valganciclovir, and remained on letermovir for at least 60 days or developed CMV viremia on letermovir within 60 days of initiation were included. The primary endpoint was the incidence of CMV viremia/disease during letermovir therapy. Secondary endpoints included changes in white blood cell (WBC) count, tacrolimus dosing, and clinically significant acute rejection.
A total of 52 patients received letermovir for an average of 8.2 months (range, 1-35 months). The average time from transplantation to letermovir initiation was 9.2 months (range, 0.9-77 months). Eight (15.4%) patients developed breakthrough CMV viremia on letermovir with a median viral load of 205 [IQR, 142.0-367.5] copies/mL; 4 of these patients were converted back to valganciclovir. Overall, 92.3% of patients completed therapy with letermovir. There were no episodes of suspected or biopsy-proven CMV disease. The majority of patients (78%) required dose reductions of tacrolimus following letermovir initiation, with no episodes of tacrolimus toxicity requiring hospitalization. WBC counts increased, on average, from 2.6 to 5.3 × 10 cells/μL (P < .001).
Letermovir holds promise as an effective and safe alternative to valganciclovir for CMV prophylaxis in HT recipients.
心脏移植（HT）后巨细胞病毒（CMV）感染与更差的预后相关。对高危患者进行抗病毒预防是标准治疗方法。缬更昔洛韦是最常用的抗病毒药物，与显著的不良事件相关，尤其是白细胞减少。来特莫韦是一种具有良好副作用特征的CMV特异性抗病毒药物，但其在HT受者中的疗效尚不清楚。本研究旨在评估来特莫韦在HT受者中预防CMV的安全性和有效性。
这项单中心回顾性分析纳入了2020年1月至2023年9月在本中心接受HT的受者。因缬更昔洛韦导致白细胞减少/中性粒细胞减少而改用 来特莫韦进行CMV预防，且在来特莫韦上至少使用60天或在开始使用来特莫韦后60天内发生CMV病毒血症的患者被纳入研究。主要终点是来特莫韦治疗期间CMV病毒血症/疾病的发生率。次要终点包括白细胞（WBC）计数、他克莫司剂量的变化以及临床上显著的急性排斥反应。
共有52例患者接受来特莫韦治疗，平均治疗时间为8.2个月（范围为1 - 35个月）。从移植到来特莫韦开始使用的平均时间为9.2个月（范围为0.9 - 77个月）。8例（15.4%）患者在使用来特莫韦时出现突破性CMV病毒血症，病毒载量中位数为205[四分位间距，142.0 - 367.5]拷贝/mL；其中4例患者重新改用缬更昔洛韦。总体而言，92.3%的患者完成了来特莫韦治疗。没有疑似或经活检证实的CMV疾病发作。大多数患者（78%）在开始使用来特莫韦后需要减少他克莫司剂量，没有发生需要住院治疗的他克莫司毒性事件。白细胞计数平均从2.6增加到5.3×10⁹细胞/μL（P < .001）。
来特莫韦有望成为缬更昔洛韦在HT受者中预防CMV的有效且安全的替代药物。
