Letermovir potently inhibits the cytomegalovirus (CMV)-terminase complex. Letermovir primary prophylaxis given for the first 3 months after allogeneic hematopoietic cell transplantation (HCT) has been shown to reduce clinically significant CMV infection and is well tolerated. Until now, only case reports or small retrospective series have been published on the use of letermovir for a secondary prophylaxis (SP) of CMV infection or diseases after HCT. Here we report the outcome of 80 consecutive CMV-seropositive adult patients included in the French compassionate program and who received letermovir as a SP after at least 1 CMV episode (infection or disease) since HCT. Letermovir was initiated at a median of 170 (49 to 1829) days after transplant and given orally for a median of 118 (26 to 396) days at the usual daily dose of 480 mg once daily and adjusted to 240 mg once daily when coadministered with cyclosporine. The donors were seronegative in 53% of the cases. Fifty patients had a current or previous graft-versus-host disease (GVHD) and 14 had experienced CMV disease since transplant. Four (5.5%) patients developed CMV breakthrough infections (n = 1) or diseases (n = 3) after the initiation of letermovir. In 3 of these 4 patients, further investigation of virologic resistance showed a CMV UL56 mutation C325Y or W, conferring the high-level letermovir resistance. One or more adverse reactions were declared by the local investigator in 15 (19%) patients. Only 2 patients stopped letermovir SP because of an adverse reaction (pruritus, 1; cytopenia, 1). In our experience, letermovir given as a SP may prevent a new CMV reactivation in a high-risk patient population and can be administered for several weeks, providing a bridge between the pre-emptive or therapeutic treatment of a CMV episode and CMV-specific immune reconstitution, giving time for tapering immunosuppressants. Prospective studies are required to confirm these results.

中文翻译：

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Letermovir用于同种异体造血细胞移植后继发性预防巨细胞病毒感染和疾病：法国同情计划的结果。

Letermovir有效抑制巨细胞病毒（CMV）-末端酶复合物。异基因造血细胞移植（HCT）后的前三个月给予莱特莫韦原发预防措施可减少临床上显着的CMV感染，并且耐受性良好。到目前为止，只有关于利特莫韦用于HCT后CMV感染或疾病的继发性预防（SP）的病例报道或小型回顾性研究。在这里，我们报告了法国同情方案中包括80名连续CMV血清反应阳性的成年患者的结果，这些患者自HCT以来至少1次CMV发作（感染或疾病）后接受了来特莫韦作为SP。利特莫韦在移植后的中位数170（49至1829）天开始，口服中位数为118（26至396）天，常规每日剂量为480 mg，每日一次，调整为240 mg，每日一次环孢菌素。在53％的病例中，供体是血清阴性的。自移植以来，已有50名患者患有当前或先前的移植物抗宿主病（GVHD），另有14名患者经历了CMV疾病。来华电影开始后，有四名（5.5％）患者出现了CMV突破性感染（n = 1）或疾病（n = 3）。在这4例患者中的3例中，对病毒学耐药性的进一步调查显示，CMV UL56突变为C325Y或W，赋予了高水平的letermovir耐药性。当地研究人员宣布有15位（19％）患者出现一种或多种不良反应。由于不良反应，仅有2例患者停止了letermovir SP（瘙痒1例；血细胞减少1例）。根据我们的经验，莱特莫韦作为SP给药可能会阻止高危患者群体中新的CMV重新激活，并且可以连续使用数周，为CMV发作的先发性或治疗性治疗与CMV特异性免疫提供了桥梁重建，给逐渐减少免疫抑制剂的时间。需要进行前瞻性研究以证实这些结果。