Extended Duration Letermovir Prophylaxis for Cytomegalovirus Infection after Cord Blood Transplantation in Adults.

Cord blood transplantation (CBT) can be complicated by a high incidence of clinically significant cytomegalovirus infection (csCMVi). We have investigated the efficacy of extended letermovir prophylaxis in seropositive adult CBT recipients. The aim was to continue prophylaxis for > 6 months (insurance permitting). By day 100, the incidence of csCMVi was 0% in 28 patients who received prophylaxis. Moreover, of 24 patients alive at day 100, none had csCMVi by day 180, having continued prophylaxis for all (n = 20) or part (n = 4) of that period. Overall, 20 patients stopped letermovir at a median of 354 days (range 119-455) post-transplant, with only 5 requiring one (n = 4) or two (n = 1) valganciclovir courses (median total duration 58 days, range 12-67) for post-prophylaxis viremia, with no subsequent csCMVi. There were no attributable letermovir toxicities. Of 62 historic controls who received acyclovir only, 51 developed csCMVi (median onset 34 days, range 5-74) for a day 100 incidence of 82% (95%CI:73-92). Seven patients developed proven/ probable CMV disease and 6 died before day 100 (3 with proven/probable CMV pneumonia). Forty-five patients required extended therapy during the first 6 months for one (n = 10), two (n = 14), or three/persistent (n = 21) csCMVi with 43/51 (84%) developing significant treatment toxicities. Letermovir is highly effective, well tolerated prophylaxis that mitigates CMV infection, CMV-related mortality and antiviral therapy toxicities in CBT recipients. Our data supports prophylaxis duration of at least 6 months after CBT.