Division of Hematology/Oncology, Department of Internal Medicine, NewYork-Presbyterian/Columbia University Irving Medical Center, New York, NY, USA.
Department of Pharmacy, NewYork-Presbyterian/Columbia University Irving Medical Center, New York, NY, USA.
Transpl Infect Dis. 2021 Apr;23(2):e13487. doi: 10.1111/tid.13487. Epub 2020 Oct 27.
Cytomegalovirus (CMV) reactivation is associated with significant morbidity and mortality after an allogeneic hematopoietic cell transplant (AHCT), and graft versus host disease (GVHD) increases the risk of CMV reactivation. Letermovir is approved for CMV prophylaxis in CMV-seropositive patients, but has only been studied through day 100 post-transplantation in the registration trial. Its efficacy in preventing CMV in patients with GVHD requiring treatment beyond the day 100 milestone has not been studied.
We retrospectively analyzed all patients who underwent an AHCT at a single center over a period of 24 months, and identified a cohort of 20 patients who received extended duration of letermovir (beyond 100 days) after the diagnosis of GVHD. The primary end point was the incidence of clinically significant CMV infection, defined as onset of CMV disease or initiation of preemptive therapy with alternative antiviral agents.
In this high-risk cohort, only one patient (5%) developed a clinically significant CMV infection, requiring preemptive therapy. No patients developed CMV organ disease. Three additional patients developed CMV viremia of ≥150 IU/mL while on letermovir and after the onset of GVHD, and none required additional treatment. Receipt of post-transplant cyclophosphamide (PTCy) and low CD4 count after the development of GVHD were associated with breakthrough CMV viremia while on extended duration letermovir.
Extended duration letermovir was efficacious in preventing clinically significant CMV infections in patients with GVHD.
巨细胞病毒（CMV）再激活与异基因造血细胞移植（AHCT）后显著的发病率和死亡率相关，移植物抗宿主病（GVHD）增加了 CMV 再激活的风险。来特莫韦被批准用于 CMV 阳性血清患者的 CMV 预防，但仅在注册试验中研究了移植后 100 天内的情况。在需要在 100 天里程碑后进行治疗的 GVHD 患者中，尚未研究其预防 CMV 的疗效。
我们回顾性分析了在一个单中心进行的 24 个月期间的所有 AHCT 患者，并确定了一组 20 名患者，这些患者在诊断为 GVHD 后接受了延长来特莫韦（超过 100 天）的治疗。主要终点是临床显著的 CMV 感染的发生率，定义为 CMV 疾病的发生或使用替代抗病毒药物进行抢先治疗。
在这个高风险队列中，只有 1 名患者（5%）发生了临床显著的 CMV 感染，需要进行抢先治疗。没有患者发生 CMV 器官疾病。另外 3 名患者在接受来特莫韦治疗并发生 GVHD 后出现了≥150IU/mL 的 CMV 血症，均无需额外治疗。在发生 GVHD 后接受移植后环磷酰胺（PTCy）和低 CD4 计数与延长来特莫韦治疗期间突破性 CMV 血症有关。
延长来特莫韦的治疗可有效预防 GVHD 患者的临床显著 CMV 感染。
