Robin Christine, Thiebaut Anne, Alain Sophie, Sicre de Fontbrune Flore, Berceanu Ana, D'Aveni Maud, Ceballos Patrice, Redjoul Rabah, Nguyen-Quoc Stéphanie, Bénard Nathalie, Pahlavan-Grumel Golriz, Cordonnier Catherine
Hematology Department, Assistance Publique-Hopitaux de Paris (AP-HP), Henri Mondor Hospital, Creteil, France; University Paris-Est-Créteil, Créteil, France.
Hematology Department, CHU Grenoble, Grenoble, France.
Biol Blood Marrow Transplant. 2020 May;26(5):978-984. doi: 10.1016/j.bbmt.2020.01.027. Epub 2020 Feb 5.
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.
来特莫韦可有效抑制巨细胞病毒（CMV）-末端酶复合物。已有研究表明，在异基因造血细胞移植（HCT）后的前3个月给予来特莫韦进行一级预防，可减少具有临床意义的CMV感染，且耐受性良好。到目前为止，关于来特莫韦用于HCT后CMV感染或疾病的二级预防（SP），仅发表了病例报告或小型回顾性系列研究。在此，我们报告了法国同情用药项目中连续纳入的80例CMV血清学阳性成年患者的结局，这些患者在自HCT后至少发生1次CMV发作（感染或疾病）后接受来特莫韦作为SP治疗。来特莫韦在移植后中位数为170（49至1829）天开始使用，以每日480mg的常用剂量口服，中位数为118（26至396）天，与环孢素合用时调整为每日240mg。53%的病例中供体血清学阴性。50例患者有当前或既往移植物抗宿主病（GVHD），14例自移植后发生过CMV疾病。4例（5.5%）患者在开始使用来特莫韦后发生CMV突破性感染（n = 1）或疾病（n = 3）。在这4例患者中的3例中，对病毒耐药性的进一步调查显示CMV UL56突变C325Y或W，赋予高水平的来特莫韦耐药性。15例（19%）患者由当地研究者申报了一种或多种不良反应。仅2例患者因不良反应（瘙痒，1例；血细胞减少，1例）停止来特莫韦SP治疗。根据我们的经验，来特莫韦作为SP治疗可预防高危患者群体中再次发生CMV激活，并且可以给药数周，在CMV发作的抢先或治疗性治疗与CMV特异性免疫重建之间架起一座桥梁，为逐渐减少免疫抑制剂的使用争取时间。需要进行前瞻性研究来证实这些结果。
