CMV Breakthrough Infrequent With New Drug Letermovir

Organ and hematopoietic stem cell transplants (HSCTs) are vital treatments, but they carry the risk of viral infections due to immune suppression. Cytomegalovirus (CMV) infections can occur in transplant recipients either from an infected donor tissue or from viral reactivation. Antiviral drugs like letermovir have been used to prevent CMV infection or reactivation after HSCT. In a recent study published in Bone Marrow Transplantation, researchers led by Dr. Danniel Zamora and Garrett A. Perchetti, investigated CMV breakthrough infections and resistance in HSCT recipients treated with letermovir.

The study, published in Nature's Bone Marrow Transplantation journal, analyzed data from 226 patients and found that approximately 40% of patients experienced CMV breakthrough, but only a few cases were clinically significant. The rate of resistance to letermovir was found to be low (<1%) at the study center. Patients who experienced clinically significant CMV reactivation received alternative antiviral therapies that effectively managed the viral reactivation. The study identified increased levels of immunosuppression, especially prolonged use of immunosuppressive steroids, as a significant risk factor for CMV reactivation. Other factors evaluated included ethnicity, presence of leukemia, and specific graft-versus-host disease (GVHD) prophylactic drug regimens. Interestingly, GVHD prophylaxis with post-transplantation cyclophosphamide or calcineurin inhibitors plus mycophenolate was associated with an increased risk of CMV reactivation.

The researchers emphasized that letermovir appeared to be safe, well-tolerated, and effective in preventing clinically significant CMV after HSCT. The low rate of letermovir resistance observed in the patient population provided reassurance. The study also highlighted the importance of real-world studies to examine adherence to guidelines for letermovir prophylaxis, identify potential barriers to implementation, and evaluate the rates of CMV infection during letermovir prophylaxis.

Moving forward, the research team aims to assess the rates of subclinical and clinically significant CMV infection during letermovir prophylaxis and potentially modify standard practice guidelines accordingly. They are also eagerly awaiting the FDA's decision on extending letermovir prophylaxis beyond 100 days post-HSCT, based on the findings from a recent phase 3 randomized clinical trial.

The study acknowledges the contributions of the UW Virology Lab, hematology-oncology colleagues, Infectious Diseases Sciences repository, clinical research data systems, and administrative staff. The research was supported by the National Institutes of Health and Fred Hutchinson Cancer Center.