Breakthrough CMV Infections on Letermovir Prophylaxis in CMV-Seropositive Allogeneic Hematopoeitic Cell Transplant (allo-HCT) Recipients

Abstract

Introduction Letermovir (LTV) is the first agent approved for CMV prophylaxis (ppx) in CMV-seropositive allo-HCT recipients. In the phase III study, the use of LTV after transplant through day 100 resulted in significantly less episodes of CMV infection and decreased mortality at week 24 when compared to placebo. Although clinical trials demonstrated the benefit of LTV, we sought to determine the efficacy of this agent and to characterize breakthrough CMV infections at our institution. Objectives and Methods This is a retrospective study evaluating the characteristics of breakthrough CMV infections in allo-HCT recipients who did or did not receive LTV for ppx. We reviewed all allo-HCT recipients who were eligible for LTV starting in March 2018 and who had reached day 100 by 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 received twice-weekly pre-emptive monitoring for CMV viremia. Results A total of 74 CMV-seropositive patients underwent allo-HCT and reached day 100 by September 2018. Fifty-three patients (72%) received LTV, and 21 patients (28%) did not. Patients on LTV for ppx were less likely to have CS-CMVi when compared to patients on no ppx (11 patients (21%) vs. 11 patients (52%), p = 0.01). The median viral load (VL) at initiation of anti-CMV therapy was similar between the 2 groups (median CMV DNA IU/mL: 1078 on LTV vs. 914 on no ppx, p = 0.57). CMV resistance genotype panels were sent after breakthrough in 8 patients (3 on LTV, 5 on no ppx) and no mutations were detected. Less patients who were on LTV ppx had a second CMV event when compared to patients who were on no ppx [1/11 (9%) vs. 3/11 (27%), respectively]. All-cause mortality was numerically higher in patients who had positive CMV VL and were not on LTV for ppx (12% no ppx vs. 7% on LTV, p = 0.57). Conclusions Patients who were on LTV for prophylaxis had less CS-CMVi, less episodes of CMV infections and trend towards lower all-cause mortality by day 100. Larger sample size is needed to further define breakthrough CMV infections while on LTV and the need for anti-CMV therapy.