A Single Center Experience of Letermovir for the Prevention of CMV Infection in CMV-Seropositive Allogeneic Cell Transplant (Allo-HCT) Recipients

Abstract

Introduction and Objectives Letermovir (LTV) is the first agent in the class of anti-CMV viral terminase inhibitors and was recently approved in the U.S. for the prevention of CMV infection in CMV-seropositive allo-HCT recipients. In the phase III study, use of LTV after transplant through day 100 resulted in significantly less CMV infections and decreased mortality at week 24 when compared to placebo. In March 2018, LTV was recommended for all CMV-seropositive allo-HCT recipients at our institution. We sought to evaluate the impact of this strategy on our patients. Methods We retrospectively evaluated all adult patients who had an allo-HCT and reached day 100 post-transplant from March – September 2018. Clinically significant CMV infection (CS-CMVi) was defined as CMV viremia or disease that resulted in initiation of anti-CMV therapy. All patients had twice-weekly CMV viral load monitoring. Patients were followed up to day 100 from HCT. Results A total of 74 patients underwent allo-HCT and reached day 100 post-transplant by end of September 2018. Fifty-three patients (72%) received LTV prophylaxis, and 21 patients (28%) did not. The most common reason for lack of LTV was insurance approval and financial issues (57%). The median age was 59 years (range: 45-66) in both groups, and 49% were male. Transplant types were similar between groups with the most common being from matched unrelated (46%) and matched related (31%) donors. The median time to engraftment was the same in both groups at 15 days (range: 12-19). Patients on LTV prophylaxis had less CS-CMVi than patients not on prophylaxis (21% vs. 52%, p\u202f=\u202f0.01). Although not statistically significant, less patients on LTV prophylaxis had probable and proven CMV disease (LTV, 6% vs. no prophylaxis, 10%; p\u202f=\u202f0.55), and less were hospitalized for treatment of CMV infections (LTV, 7% vs. no prophylaxis, 12%; p\u202f=\u202f0.57). All-cause mortality at day 100 was numerically higher in the group without prophylaxis (no prophylaxis, 14% vs. LTV, 4%; p\u202f=\u202f0.10). Conclusions This is the first ongoing study evaluating the impact of LTV for prevention of CMV infection. We found that LTV reduced the incidence of CS-CMVi including a trend towards decreased mortality. Given its demonstrated benefits, LTV should be considered in all CMV-seropositive allo-HCT recipients.