In an international phase III clinical trial, the novel antiviral agent letermovir was shown to lower patients’ risk of developing cytomegalovirus (CMV) infection following allogeneic hematopoietic cell transplantation (AHCT).
The study, presented at the 2017 combined annual meetings of the Center for International Blood & Marrow Transplant Research (CIBMTR) and the American Society for Blood and Marrow Transplantation (ASBMT), included 495 adult patients enrolled from 67 research centers in 20 countries. All patients underwent HCT to treat hematologic diseases and carried a dormant CMV infection from earlier in life.
From June 2014 to March 2016, patients were randomized 2:1 to receive either prophylactic letermovir 480 mg/day (n=325) or placebo (n=170) for at least 14 weeks post-AHCT. On average, treatment began 9 days post-HCT.
At six months, fewer patients in the letermovir group developed a CMV infection, compared with placebo-treated patients (38% vs. 61%; p<0.0001).
The researchers reported that treatment with letermovir had “no increased myelotoxicity or nephrotoxicity,” and the most common adverse events (AEs) with letermovir were graft-versus-host disease (39%), diarrhea (26%), and nausea (27%). Fifty-six patients discontinued letermovir (17.2%), compared with 27 patients who discontinued placebo (15.9%). Most treatment discontinuations were related to AEs (1.8% in the letermovir group and 0.6% in the placebo group), death without CMV (6.8% and 7.1%), or other causes (6.8% and 8.2%).
“The goal was to suppress the virus before it has a chance to become active,” the study’s lead author Francisco Marty, MD, said during his presentation of the results. “The results of this trial offer encouragement that letermovir can [provide] a new strategy for donor HCT patients in preventing the emergence of CMV infection following transplant.” The results with letermovir will need to be compared with currently available forms of CMV prevention, which limits the study’s findings.
Source: Marty FM, Ljungman PT, Chemaly RF, et al. A phase III randomized, double-blind, placebo-controlled trial of letermovir (LET) for prevention of cytomegalovirus (CMV) infection in adult CMV-seropositive recipients of allogeneic hematopoietic cell transplantation (HCT). Abstract presented at the 2017 BMT Tandem Meetings; Orlando, Florida; Dana-Farber Cancer Institute press release, February 22, 2017.