Letermovir for cytomegalovirus prophylaxis in hematopoietic-cell transplantation.
N Engl J Med
; 370(19): 1781-9, 2014 May 08.
Article
in En
| MEDLINE
| ID: mdl-24806159
ABSTRACT
BACKGROUND:
Cytomegalovirus (CMV) infection is a leading cause of illness and death in patients who have undergone allogeneic hematopoietic-cell transplantation. Available treatments are restricted by clinically significant toxic effects and drug resistance.METHODS:
In this phase 2 study, we evaluated the effect of letermovir (also known as AIC246), a new anti-CMV drug with a novel mechanism of action, on the incidence and time to onset of prophylaxis failure in CMV-seropositive recipients of allogeneic hematopoietic-cell transplants from matched related or unrelated donors. From March 2010 through October 2011, we randomly assigned 131 transplant recipients in a 31 ratio to three sequential study cohorts according to a double-blind design. Patients received oral letermovir (at a dose of 60, 120, or 240 mg per day, or matching placebo) for 12 weeks after engraftment. The primary end point was all-cause prophylaxis failure, defined as discontinuation of the study drug because of CMV antigen or DNA detection, end-organ disease, or any other cause. Patients underwent weekly surveillance for CMV infection.RESULTS:
The reduction in the incidence of all-cause prophylaxis failure was dose-dependent. The incidence of prophylaxis failure with letermovir, as compared with placebo, was 48% versus 64% at a daily letermovir dose of 60 mg (P=0.32), 32% at a dose of 120 mg (P=0.01), and 29% at a dose of 240 mg (P=0.007). Kaplan-Meier time-to-onset profiles for prophylaxis failure showed a significant difference in the comparison of letermovir at a dose of 240 mg per day with placebo (P=0.002). The safety profile of letermovir was similar to placebo, with no indication of hematologic toxicity or nephrotoxicity.CONCLUSIONS:
Letermovir, as compared with placebo, was effective in reducing the incidence of CMV infection in recipients of allogeneic hematopoietic-cell transplants. The highest dose (240 mg per day) had the greatest anti-CMV activity, with an acceptable safety profile. (Funded by AiCuris; ClinicalTrials.gov number, NCT01063829.).
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Antiviral Agents
/
Quinazolines
/
Opportunistic Infections
/
Immunocompromised Host
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Cytomegalovirus Infections
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Hematopoietic Stem Cell Transplantation
/
Acetates
Type of study:
Clinical_trials
/
Incidence_studies
/
Prognostic_studies
Limits:
Adult
/
Humans
Language:
En
Journal:
N Engl J Med
Year:
2014
Document type:
Article