Of the 738 patients screened, 570 were randomized to oral or IV treatment with letermovir (480 mg/day or half that dose in patients receiving concomitant cyclosporine; n=376) or placebo (n=194) for 14 weeks following HCT, with a follow-up to week 48. Treatment began at a median of 9 days post-HCT. Two patients in each arm were not treated, for a final patient tally of 373 and 192 in the letermovir and placebo arm, respectively (total n=565).
All patients were ≥18 years of age and had undetectable plasma CMV when screened for participation. A variety of criteria were used to judge if patients were at high-risk of CMV infection; 32.4% and 28.1% of patients in the letermovir and placebo arms, respectively, were judged to be high-risk.
At baseline, the 2 study arms were comparable in gender, race, age, geographic region, immunosuppression regimen used, donor type, stem cell type, and conditioning regimen used. The trial’s primary endpoint was the development of clinically significant CMV infection (CS-CMVi) at week 24 following HCT.
The rate of all-cause mortality at week 24 was 10.6% (95% confidence interval [CI] 7.4 to 13.9) and 15.5% (95% CI 10.1 to 20.9) in the letermovir and placebo arm, respectively (P
= .0560). The treatment-related, non-significant, survival advantage was maintained through week 48.
At week 24, CS-CMVi had developed in 37.5% of patients in the letermovir arm and 60.6% of those in the placebo arm (P
< .0001). The risk of all-cause death at 48 weeks in these patients was lower in the letermovir arm (17.7%) than in the placebo arm (29.5%).
The week-48 all-cause death rate in patients who did not develop CS-CMVi was 19.7% in the letermovir arm and 18.3% in the placebo arm.
The causes of death were comparable in the 2 arms. Most common causes were acute myeloid leukemia, respiratory failure, graft-versus-host disease, sepsis, and septic shock.
“Letermovir was associated with lower all-cause mortality compared with placebo through week 24 and week 48 post-HCT, although these differences were not clinically significant. The risk of death associated with placebo versus letermovir was substantially higher in participants with CS-CMVi, despite the use of pre-emptive therapy, than in participants without CS-CMVi,” wrote the researchers.
They also noted that the risk of mortality in the subset of patients with CS-CMVi was lower in the letermovir group than in the placebo group, “suggesting that letermovir prophylaxis also affects mortality in participants who develop CMV.”
“I think that the phase 2 and 3 data are going to change the way we do things in HCT, with the use of a prevention strategy and a move away from a pre-emptive strategy,” said Dr. Chemaly. The data will inform the approval process, which is anticipated in the coming year. Further down the line, the treatment will be explored in solid organ transplants.
Roy Chemaly, MD, MPH: Chimerix Inc., grants, and personal fees; Merk & Co. Inc., grants, and personal fees; Novartis, grant; Astellas, personal fees; Oxford Immunotec, personal fees.
Poster Session: Adult Viral Infection
Poster 1029. A Mortality Analysis of Letermovir Prophylaxis for Cytomegalovirus (CMV) in CMV-Seropositive Recipients of Allogeneic Hematopoietic Cell Transplantation
Brian Hoyle, PhD, is a medical and science writer and editor from Halifax, Nova Scotia, Canada. He has been a full-time freelance writer/editor for over 15 years. Prior to that, he was a research microbiologist and lab manager of a provincial government water testing lab. He can be reached at email@example.com.
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