Perchetti GA, Biernacki MA, Xie H, et al. Cytomegalovirus Breakthrough and Resistance During Letermovir Prophylaxis. Nature. 2023; (doi: 10.1038/s41409-023-01920-w).
Researchers report letermovir can suppress clinically significant cytomegalovirus (CMV) infection following allogeneic hematopoietic cell transplantation (HCT), but subclinical CMV reactivation was common at the test center. The study involved 226 CMV-seropositive HCT recipients who received prophylaxis with letermovir. In all, 47% (7/15) of patients with CMV DNAemia ≥200 IU/mL were genotyped for UL56 CMV resistance, and one umbilical cord blood recipient had a C325Y resistance mutation. Breakthrough CMV at any level was identified in 42% (N=95), 19% (N=43), and 7% (N=15) of patients, with ≥150 IU/mL, and ≥500 IU/mL, respectively. The strongest risk factor for CMV at all rated viral thresholds was cumulative steroid exposure. Also associated with a higher risk of CMV reactivation at any level is graft-versus-host disease prophylaxis using post-transplantation cyclophosphamide or calcineurin inhibitors combined with mycophenolate. Other antivirals were successful in treating rare occurrences of de novo letermovir resistance.
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