Letermovir Prophylaxis After Transplant for Cytomegalovirus
Orlando, FL—Prophylaxis with letermovir beginning after hematopoietic-cell transplantation (HCT) and lasting through 100 days reduced the risk for clinically significant cytomegalovirus (CMV) infection. Furthermore, letermovir was associated with lower all-cause mortality compared with placebo, reported Francisco M. Marty, MD, Associate Professor of Medicine, Harvard Medical School, Boston, at the 2017 BMT Tandem Meetings.
Data from a randomized clinical trial showed a reduction in clinically significant CMV through week 24, from 60.6% in the placebo arm to 37.5% in the letermovir arm (P <.0001). The most common indication for HCT was acute myeloid leukemia, which was present in 38% of patients in each treatment group.
Letermovir, a first-in-class agent that inhibits the terminase complex by binding to UL56, was well-tolerated, with minimal attributable toxicity. “Letermovir primary prophylaxis of CMV infection may represent a new strategy for the prevention of CMV in allogeneic transplantation,” said Dr Marty.
CMV seropositivity and early CMV reactivation are associated with increased mortality in HCT. “Antiviral prophylaxis may be a way to further address the impact of CMV in allogeneic transplantation,” he added.
Overall, 570 patients were randomized in a 2:1 ratio to receive letermovir 480 mg daily (or 240 mg daily if patients were receiving concomitant cyclosporine because of drug interactions) or placebo through week 14 after HCT.
Patients who had clinically significant CMV discontinued the study drug and received anti-CMV treatment.
Overall, 78.5% of patients in the letermovir arm and 70.1% of patients in the placebo arm remained in the study through week 24, with 20.7% and 28.9%, respectively, discontinuing treatment prematurely. The main reason for treatment discontinuation was death, which occurred in 9.8% of patients in the letermovir arm and 14.4% of patients in the placebo arm.
Of the patients who discontinued treatment for any reason or who had missing data at week 24, 17.5% of patients in the letermovir arm had clinically significant CMV compared with 41.8% in the placebo arm. Overall, 16% of letermovir recipients received preemptive treatment for CMV versus 37.6% of placebo recipients.
The median treatment duration was 82 days in the letermovir arm and 56 days in the placebo arm. Drug-related adverse events were reported in 16.9% of patients in the letermovir arm versus 12% of patients in the placebo arm. The most common adverse events with letermovir were graft-versus-host disease (39.1%), nausea (26.5%), diarrhea (26.0%), fever (20.6%), and rash (20.4%).