Letermovir Prevents Cytomegalovirus Infection and Improves Survival Post-Transplant

Prophylactic treatment with letermovir improved overall survival (OS) and significantly decreased the incidence of clinically significant cytomegalovirus (CMV) infection in patients who underwent allogeneic hematopoietic cell transplantation (alloHCT), according to results from a single-center study presented at the 2021 American Society of Clinical Oncology Annual Meeting.

Lead author Delaney Wolfe, PharmD, of The Ohio State University Comprehensive Cancer Center, and colleagues also reported that patients who developed acute graft-versus-host disease (GVHD) showed significantly less CMV viremia, suggesting that these patients may benefit from continued letermovir prophylaxis beyond 100 days.

CMV is the most common infection seen in patients after alloHCT and is associated with increased mortality, the researchers explained. Human leukocyte antigen (HLA) mismatch, high-dose corticosteroids, and GVHD all contribute to the risk of CMV infection. Patients who experience GVHD have a further heightened risk of CMV infection due to the use of immunosuppressive therapies to treat GVHD.

In this single-center, retrospective study, investigators enrolled a total of 262 CMV-seropositive patients who underwent alloHCT between June 1, 2016, and June 30, 2020, to determine the effectiveness of extended letermovir in patients who develop GVHD.

A total of 119 patients had received letermovir prophylaxis, while 149 had not. Of the 111 patients who were treated for clinically significant CMV infection, 81 did not receive letermovir (57%), compared with 29 patients who did (24%).

Incidence of CMV viremia was significantly reduced in all patients who received letermovir (hazard ratio [HR] = 0.21; p<0.001), the authors reported (TABLE). After adjusting for age, gender, GVHD prophylaxis, and the use of antithymocyte globulin or T-cell–depleted graft, CMV viremia was also significantly reduced among patients who developed grade >2 acute GVHD within 200 days of undergoing alloHCT (HR=0.12; p<0.001).

Letermovir prophylaxis was associated with improved OS (HR=0.46; p=0.04) and lower rates of non-relapse mortality (HR=0.41; p=0.04), the researchers added.

The median duration of letermovir prophylaxis was 95 days, while nine patients continued letermovir therapy indefinitely for recurrent CMV viremia. While these results suggest a role for continued letermovir prophylaxis in transplant recipients, the findings from this single-center analysis may not be generalizable to other patient populations. Further studies are required to determine the effectiveness of letermovir prophylaxis past day 100 in patients who develop GVHD, the authors concluded.

This study is limited by changes in clinical practice over time that may have impacted the results and the investigators’ inability to assess letermovir compliance.

The authors report no relevant conflicts of interest.

Reference

Wolfe D, Zhao Q, Siegel EG, et al. Letermovir prophylaxis and cytomegalovirus reactivation in adult allogeneic hematopoietic cell transplant recipients with graft versus host disease. Abstract #7004. Presented at the 2021 American Society of Clinical Oncology Annual Meeting, June 4-8, 2021.

TABLE. Clinically significant CMV infection, CMV viremia, and mortality in patients who received letermovir prophylaxis vs. patients who did not receive letermovir

No Letermovir

(n=143)

Letermovir

(n=119

p-value
Clinically significant CMV infection 81 (56.6%) 29 (24.4%) <0.001
CMV viremia 108 (75.5%) 47 (39.5%) <0.01
Peak CMV viremia in IU/mL, median (range) 1003 (51-81300) 770 (51-18178) 0.03
Mortality, all types 62 (43.4%) 38 (31.9%) 0.65
    Treatment-related 21 (14.6%) 15 (12.6%)
    Non-relapsed 14 (9.7%) 10 (8.4%)
    Disease-related 27 (18.8%) 13 (10.9%)