Golob Stephanie, Batra Jaya, DeFilippis Ersilia M, Uriel Matan, Carey Matt, Gaine Maureen, Mabasa Angelo, Fried Justin, Raikelkar Jayant, Restaino Susan, Hi Lee Sun, Latif Farhana, Yuzefpolskaya Melana, Colombo Paolo C, Choe Jason, Majure David, Jennings Douglas, Pereira Marcus R, Clerkin Kevin, Sayer Gabriel, Uriel Nir
Division of Cardiology, Department of Medicine, Columbia University College of Physicians and Surgeons, New York, New York, USA.
Division of Cardiology, Department of Medicine, Cornell University, Ithaca, New York, USA.
Clin Transplant. 2022 Dec;36(12):e14808. doi: 10.1111/ctr.14808. Epub 2022 Oct 26.
Letermovir is a novel agent for the prevention of cytomegalovirus (CMV) infection and disease that, unlike traditional CMV DNA polymerase inhibitors, does not carry the risk of myelosuppression. The purpose of this study was to evaluate the safety, efficacy, and clinical application of letermovir for CMV prophylaxis in heart transplant (HT) recipients. Between November 1, 2019, and October 1, 2021, at a single, tertiary care hospital, 17 HT recipients were initiated on letermovir due to leukopenia while on valganciclovir. Fifteen (88%) had high-risk mismatch (CMV D+/R-). Median time on letermovir was 5 months (interquartile range, 2-8 months.) At the end of the study period, nine of 17 patients (52.9%) were still on letermovir and four of the 17 (23.5%) had successfully completed the prophylaxis window on letermovir and been switched to the pre-emptive strategy. One patient developed clinically significant CMV viremia in the setting of being unable to obtain medication due to insurance barriers but was later successfully restarted on letermovir. One patient was unable to tolerate letermovir due to symptoms of headache and myalgias. Two patients developed low-level non-clinically significant CMV viremia and were switched back to valacyclovir. All patients had tacrolimus dosages reduced at time of letermovir initiation to minimize the risk of supratherapeutic tacrolimus concentration. One patient required hospitalization due to symptomatic tacrolimus toxicity. For HT recipients who cannot tolerate valganciclovir, letermovir presents an alternative for CMV prophylaxis. Close monitoring for breakthrough CMV and calcineurin inhibitor levels is necessary. Larger studies are required to further delineate its use and help provide further evidence of its safety and efficacy.
来特莫韦是一种预防巨细胞病毒（CMV）感染和疾病的新型药物，与传统的CMV DNA聚合酶抑制剂不同，它不存在骨髓抑制风险。本研究的目的是评估来特莫韦在心脏移植（HT）受者中预防CMV的安全性、有效性和临床应用。在2019年11月1日至2021年10月1日期间，在一家三级医疗中心，17名HT受者在使用缬更昔洛韦时因白细胞减少而开始使用来特莫韦。其中15名（88%）存在高风险不匹配（CMV D+/R-）。来特莫韦的中位使用时间为5个月（四分位间距，2 - 8个月）。在研究期结束时，17名患者中有9名（52.9%）仍在使用来特莫韦，17名中有4名（23.5%）已成功完成来特莫韦的预防期并转为抢先治疗策略。一名患者因保险障碍无法获得药物而出现具有临床意义的CMV病毒血症，但后来成功重新开始使用来特莫韦。一名患者因头痛和肌痛症状无法耐受来特莫韦。两名患者出现低水平的无临床意义的CMV病毒血症，并换回伐昔洛韦。所有患者在开始使用来特莫韦时均降低了他克莫司剂量，以尽量降低他克莫司浓度超治疗水平的风险。一名患者因有症状的他克莫司毒性而需要住院治疗。对于不能耐受缬更昔洛韦的HT受者，来特莫韦是CMV预防的一种替代药物。密切监测CMV突破和钙调神经磷酸酶抑制剂水平是必要的。需要进行更大规模的研究以进一步明确其用法，并有助于提供其安全性和有效性的进一步证据。
