BACKGROUND: The cytomegalovirus (CMV) risk persistence beyond the day 100 prophylaxis period after allogeneic hematopoietic stem cell transplant (HSCT) remains unclear; however, in the registration study for letermovir, the incidence of CMV reactivation increased significantly between weeks 14 and 24. A recent phase 3 trial evaluated extending letermovir prophylaxis from 100 to 200 days after allogeneic HSCT for additional benefit compared with placebo in patients with a high risk for clinically significant CMV (CS-CMV) infection beyond 100 days after allogeneic HSCT. The study showed significantly lower CS-CMV at week 28 in the extended letermovir group. However, the use of posttransplant cyclophosphamide was not part of the inclusion criteria. Two studies concluded that posttransplant cyclophosphamide, regardless of donor, is associated with a higher incidence of CS-CMV and augments the risk for CMV seropositivity. This institute utilizes posttransplant cyclophosphamide for all allogeneic HSCT graft-versus-host disease (GVHD) prophylaxis leading to a potential greater risk for CMV-related adverse events (AEs).
OBJECTIVES: To evaluate the occurrence of CMV-related AEs to determine if they are occurring in seropositive donor transplants because of increased risk with posttransplant cyclophosphamide and to establish whether extended letermovir yields benefit. The primary end point was the difference in the occurrence of CMV-related AEs for seronegative recipients of seropositive donor organs (CMV R-/D+) versus seropositive recipients of seronegative donor organs (CMV R+/D-). The secondary end points included the differences in CMV-related AEs for patients receiving posttransplant cyclophosphamide versus those who did not receive posttransplant cyclophosphamide; those who received letermovir prophylaxis compared with those who did not; and the duration of letermovir up to day 100 versus letermovir past day 100.
METHODS: In this single-center study at Geisinger Medical Center in Danville, PA, we collected data from electronic health records between June 1, 2013, and June 30, 2023, on allogeneic HSCT recipients aged ≥18 years who were CMV seropositive from the recipient, the donor, or both.
RESULTS: CMV R-/D+ patients did not have CMV reactivation or CS-CMV in this study. However, recipient-positive, donor-positive patients were more likely to have CMV reactivation than CMV R+/D- or CMV R-/D+ patients (P=.049). Of the patients who did not receive letermovir prophylaxis, 35.7% had CMV-related AEs compared with 16.3% of patients who received letermovir. Although letermovir treatment duration affected the time to CMV-related AEs, statistical significance was not observed with interventions of either posttransplant cyclophosphamide or letermovir regarding CMV-related AEs.
CONCLUSION: Despite all CMV R-/D+ patients receiving posttransplant cyclophosphamide for GVHD prophylaxis, there were no CMV-related AEs. Our data suggest that the longer letermovir is received, the later CMV-related AEs occurred after allogeneic HSCT.
KEY WORDS: adverse events, allogeneic hematopoietic stem cell transplant, CMV reactivation, cyclophosphamide, cytomegalovirus, donor, graft-versus-host disease, letermovir, prophylaxis, recipient, transplant
J Hematol Oncol Pharm.
2026;16(5):1-11
Disclosures at the end of text