Evaluating Real-World Experience With Maribavir for Treatment of Refractory/Resistant Cytomegalovirus in Renal Transplant Recipients

IF 1.9 4区医学 Q2 SURGERY Clinical Transplantation Pub Date : 2024-10-20 DOI:10.1111/ctr.15480

Vivek B. Beechar, Varun K. Phadke, Stephanie M. Pouch, Aneesh K. Mehta, Geeta Karadkhele, Christian P. Larsen, Michael H. Woodworth

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Abstract

Introduction

Maribavir was recently approved by the FDA, expanding treatment options for post–solid-organ transplant refractory/resistant CMV. We sought to describe the post–marketing experience with maribavir at a large academic transplant center.

Methods

This was a retrospective observational study of all renal transplant recipients treated with maribavir for refractory/resistant CMV DNAemia/disease. CMV viral loads, immunosuppression regimens and management, resistance testing, and antiviral therapy durations were reviewed. Outcomes of interest included treatment success, defined as undetectable CMV DNAemia for two consecutive weeks or detected but unquantifiable DNAemia for five consecutive weeks, as well as the emergence of antiviral resistance, and recurrent DNAemia.

Results

From 2021 to 2023, 5/10 (50%) patients achieved durable virologic suppression with maribavir (classified as responders). Among responders, 2/5 (40%) experienced low-level CMV DNAemia recurrence (defined as a viral load less than 1000 IU/mL) within 8 weeks of antiviral discontinuation. Among nonresponders, 2/3 (66.7%) were found to have UL97 protein mutations associated with maribavir resistance identified 85 and 75 days after initiation of maribavir. Two patients are currently on maribavir with clinical outcomes that are yet to be determined. Responders had a mean reduction of 200 mg (SD—274 mg) in mycophenolate dosing with nonresponders having a mean increase of 167 mg (SD—764 mg).

Conclusions

Maribavir, often in conjunction with mycophenolate dose reduction, was effective for many patients with refractory/resistant CMV DNAemia at our transplant center, though several experienced recurrent DNAemia. In patients who did not respond to therapy, resistance to maribavir was frequently detected. Clinicians treating these patients should remain vigilant for rebound CMV DNAemia and consider repeat antiviral resistance testing.

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评估使用马利巴韦治疗肾移植受者难治/耐药巨细胞病毒的实际经验

导言：美国食品药品管理局最近批准了马利巴韦，扩大了实体器官移植后难治/耐药 CMV 的治疗选择范围。我们试图描述一家大型学术移植中心使用马利巴韦的上市后经验。方法这是一项回顾性观察研究，研究对象是所有接受马利巴韦治疗的肾移植受者，他们都曾接受过难治/耐药 CMV DNA 血症/疾病的治疗。研究回顾了 CMV 病毒载量、免疫抑制方案和管理、耐药性检测和抗病毒治疗持续时间。研究结果包括治疗成功（定义为连续两周检测不到 CMV DNA 血症或连续五周检测到但无法量化的 DNA 血症）、抗病毒耐药性的出现以及 DNA 血症的复发。结果从 2021 年到 2023 年，5/10（50%）名患者在使用马利巴韦后实现了持久的病毒学抑制（被归类为应答者）。在应答者中，2/5（40%）的患者在停药 8 周内出现低水平 CMV DNA 血症复发（定义为病毒载量低于 1000 IU/mL）。在无应答患者中，2/3（66.7%）的患者在开始服用马利巴韦 85 天和 75 天后发现与马利巴韦耐药相关的 UL97 蛋白突变。两名患者目前仍在服用马利巴韦，临床结果尚待确定。应答者的霉酚酸盐用量平均减少了 200 毫克（标度值为 274 毫克），而无应答者的用量平均增加了 167 毫克（标度值为 764 毫克）。结论在我们的移植中心，马利巴韦通常与降低霉酚酸酯剂量相结合，对许多难治/耐药CMV DNA血症患者有效，但也有一些患者出现了DNA血症复发。在对治疗无反应的患者中，经常检测到对马利巴韦的耐药性。治疗这些患者的临床医生应时刻警惕CMV DNA血症的反弹，并考虑重复进行抗病毒耐药性检测。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Clinical Transplantation 医学-外科

CiteScore

3.70

自引率

4.80%

发文量

286

审稿时长

2 months

期刊介绍： Clinical Transplantation: The Journal of Clinical and Translational Research aims to serve as a channel of rapid communication for all those involved in the care of patients who require, or have had, organ or tissue transplants, including: kidney, intestine, liver, pancreas, islets, heart, heart valves, lung, bone marrow, cornea, skin, bone, and cartilage, viable or stored. Published monthly, Clinical Transplantation’s scope is focused on the complete spectrum of present transplant therapies, as well as also those that are experimental or may become possible in future. Topics include: Immunology and immunosuppression; Patient preparation; Social, ethical, and psychological issues; Complications, short- and long-term results; Artificial organs; Donation and preservation of organ and tissue; Translational studies; Advances in tissue typing; Updates on transplant pathology;. Clinical and translational studies are particularly welcome, as well as focused reviews. Full-length papers and short communications are invited. Clinical reviews are encouraged, as well as seminal papers in basic science which might lead to immediate clinical application. Prominence is regularly given to the results of cooperative surveys conducted by the organ and tissue transplant registries. Clinical Transplantation: The Journal of Clinical and Translational Research is essential reading for clinicians and researchers in the diverse field of transplantation: surgeons; clinical immunologists; cryobiologists; hematologists; gastroenterologists; hepatologists; pulmonologists; nephrologists; cardiologists; and endocrinologists. It will also be of interest to sociologists, psychologists, research workers, and to all health professionals whose combined efforts will improve the prognosis of transplant recipients.