Hematology Service, Hospital Clínico Universitario, INCLIVA Health Research Institute, Valencia, Spain.
Department of Medicine, School of Medicine, University of Valencia, Valencia, Spain.
J Med Virol. 2023 Aug;95(8):e29005. doi: 10.1002/jmv.29005.
On November 7, 2017, the US Food and Drug Administration approved the use of letermovir (LMV) for prophylaxis of cytomegalovirus (CMV) infection in adult CMV-seropositive allogeneic stem cell transplant recipients. After 6 years of use, a large body of real-world experience has been accumulated that validates the Phase III clinical trial results, in which LMV was shown to significantly reduce the risk of clinically significant CMV infection-defined as CMV end-organ disease or CMV DNAemia requiring pre-emptive antiviral therapy (PET)-and increase survival up to Week 24 after treatment inception. Notwithstanding, several issues still need to be settled, thus further investigation is required. First, since viral DNA may accumulate as a result of LMV-driven abortive CMV infection, what is the optimal viral load threshold in the blood that would prompt LMV prophylaxis interruption and PET inception? Should this be adapted to the patient's risk? Second, what is the impact of LMV prophylaxis on the reconstitution of functional CMV-specific T-cell responses? Would it be a wise approach to individually tailor the duration of LMV treatment according to the number of peripheral blood CMV-specific T cells at the end of regular prophylaxis? Third, how frequently do LMV-resistant strains arise while patients are on LMV prophylaxis and how could this be minimized? Here, we discuss the literature addressing these topics.
2017 年 11 月 7 日，美国食品和药物管理局批准使用来特莫韦（LMV）预防 CMV 血清阳性的异基因造血干细胞移植受者发生 CMV 感染。在使用 6 年后，积累了大量真实世界的经验，验证了 III 期临床试验结果，表明 LMV 可显著降低临床显著 CMV 感染的风险，即 CMV 终末器官疾病或需要抢先抗病毒治疗（PET）的 CMV DNA 血症，并提高治疗开始后第 24 周的生存率。尽管如此，仍有几个问题需要解决，因此需要进一步研究。首先，由于 LMV 驱动的中止性 CMV 感染可能导致病毒 DNA 积累，那么血液中最佳的病毒载量阈值是多少，才能促使中断 LMV 预防和开始 PET？是否应该根据患者的风险进行调整？其次，LMV 预防对功能性 CMV 特异性 T 细胞反应的重建有何影响？根据常规预防结束时外周血 CMV 特异性 T 细胞的数量，个体化调整 LMV 治疗的持续时间是否是明智的方法？第三，患者接受 LMV 预防时 LMV 耐药株的出现频率如何，如何将其最小化？在这里，我们将讨论针对这些问题的文献。
