Cheng Matthew P, Gonzalez-Bocco Isabel H, Arbonna-Haddad Esther, Aleissa Muneerah, Chen Kaiwen, Zhou Eric, Beluch Katherine, Cho Alyssa, Burchett Sandra, Moulton Elizabeth, Desjardins Michaël, Baden Lindsey R, Koo Sophia, Letourneau Alyssa R, Hammond Sarah P, Ritz Jerome, Soiffer Robert, Issa Nicolas C, Kim Haesook T, Sherman Amy C
Division of Infectious Diseases, Department of Medicine, McGill University Health Centre, Montreal, Quebec, Canada.
Division of Medical Microbiology, Department of Laboratory Medicine, McGill University Health Centre, Montreal, Quebec, Canada.
J Assoc Med Microbiol Infect Dis Can. 2025 Jan 20;10(1):6-14. doi: 10.3138/jammi-2024-0016. eCollection 2025 Mar.
Refractory or resistant cytomegalovirus (CMV) infection and disease pose a significant challenge in immunocompromised patients, including solid organ transplant (SOT) and allogeneic hematopoietic cell transplant (allo-HCT) recipients. This study aimed to evaluate letermovir as a treatment for patients with CMV infection or disease.
We performed an open-label, phase II non-randomized clinical trial. Adult and paediatric (≥12 years of age) patients who had undergone an SOT or allo-HCT and who required antiviral treatment for refractory or resistant CMV or who had CMV with concurrent organ dysfunction were eligible. Patients received letermovir treatment daily for up to 12 weeks with an optional additional 12 weeks of therapy for secondary prophylaxis if clinically indicated. The primary objectives were to evaluate the safety and efficacy of letermovir treatment based upon virological and clinical responses.
Ten patients were enrolled in the study, and seven patients completed the study treatment and follow-up period. The overall virological response (defined as a complete virological response at the end of the study period) rate was 60% in the study population. The study drug was well tolerated, as only two patients experienced study drug-related toxicity and only one grade 3 toxicity (elevated ALT) was observed. Letermovir was not associated with acute kidney injury, hepatotoxicity, cardiac arrhythmias, or bone marrow suppression.
In this limited sample, letermovir for CMV treatment was safe and well tolerated. Further research is needed to determine if letermovir can be used for the treatment of refractory or resistant CMV infection or disease.
难治性或耐药性巨细胞病毒(CMV)感染及疾病给免疫功能低下的患者带来了重大挑战,这些患者包括实体器官移植(SOT)受者和异基因造血细胞移植(allo-HCT)受者。本研究旨在评估来特莫韦作为CMV感染或疾病患者的治疗药物。
我们开展了一项开放标签的II期非随机临床试验。接受过SOT或allo-HCT且因难治性或耐药性CMV需要抗病毒治疗或患有CMV并伴有器官功能障碍的成人及儿科(≥12岁)患者符合入选标准。患者每天接受来特莫韦治疗,最长可达12周,若有临床指征,可选择额外进行12周的二级预防治疗。主要目标是根据病毒学和临床反应评估来特莫韦治疗的安全性和有效性。
10名患者入组本研究,7名患者完成了研究治疗及随访期。研究人群的总体病毒学反应(定义为研究期结束时的完全病毒学反应)率为60%。研究药物耐受性良好,仅有2名患者出现与研究药物相关的毒性反应,仅观察到1例3级毒性反应(ALT升高)。来特莫韦与急性肾损伤、肝毒性、心律失常或骨髓抑制无关。
在这个有限的样本中,用于治疗CMV的来特莫韦安全且耐受性良好。需要进一步研究以确定来特莫韦是否可用于治疗难治性或耐药性CMV感染或疾病。