Letermovir—a first-in-class inhibitor of the terminase complex of cytomegalovirus (CMV)—protects from viral infection in CMV-seropositive individuals following allogeneic hematopoietic cell transplantation (HCT). The good news from the randomized, double-blind, placebo-controlled trial (NCT02137772) was presented in a poster session October 6, 2017, at the ID Week 2017 meeting in San Diego, California. The presenter was Johan Maertens, MD PhD, Universitaire Ziekenhuizen Leuven, in Leuven, Belgium.
An essential aspect of HCT is immunosuppression. Although this paves the way for transplant success, it can lay the patients open for infections that can be life-threatening, such as CMV infection. “CMV is one of the most common infections we see after transplant. In high-risk transplant patients, the rate can be upwards of 80%, with rates of 35% to 40% in lower-risk patients,” Roy F. Chemaly, MD, MPH, from the University of Texas MD Anderson Cancer Center in Houston, Texas told Contagion®
. Dr. Chemaly was involved in the phase 2 and 3 trials.
The standard of care for CMV infection is intravenous (IV) ganciclovir or its oral prolog, valganciclovir, or the intravenous application of either foscarnet or cidofovir. These therapies work, but at the cost of adverse effects that include myelosuppression and renal toxicity. Therefore, they can only be used for a short time after the presence of the virus is detected. Having a prophylactic CMV option would be a game changer.
The high rates of CMV infection in transplant recipients are a consequence of the acquisition of CMV in the childhood years in most of us. The virus becomes latent and asymptomatic. Conditions like prolonged immunosuppression can spur its reactivation. The idea behind the use of letermovir, according to Dr. Chemaly, is that prophylactic therapy initiated soon after HCT can keep the virus in check and prevent infection.
The normal post-HCT strategy for the past 15 years or so has been to check the blood for the presence of CMV nucleic acid at a time when the person is still asymptomatic. If detected, antiviral treatment is begun pre-emptively for a short time to try and quell the infection. Prophylactic use has not been the norm because of the toxicities of the drugs. “What we are trying to do now with letermovir is to prevent the infection from even appearing in the blood. The drug’s efficacy and safety allow us to use it from the get-go during the high-risk period following transplantation,” explained Dr. Chemaly.
The latest trial conducted at 67 sites in 20 countries from June 2014 to March 2016 was spurred by data from a phase 2 dose-escalation trial (60, 120, and 240 mg/day, once-daily for 12 weeks) that demonstrated the efficacy and safety of letermovir 240 mg/day in preventing CMV infection in CMV-seropositive HCT recipients.