New antiviral drug cuts cytomegalovirus infection

In a significant advance in improving the safety of donor stem cell transplants, a major clinical trial led by researchers at Dana-Farber Cancer Institute and Brigham and Women’s Hospital (BWH) has shown that a novel agent can protect against the most common viral infection that patients face after transplantation.

The results represent a breakthrough in a decade-long effort to identify an effective drug for the prevention of cytomegalovirus (CMV) infection in transplant patients that doesn’t produce side effects that negate the benefit of the drug itself, the study authors said.

The study, which involved 565 adult patients at 67 research centres in 20 countries, compared letermovir to placebo in preventing an active CMV infection following transplant with donor stem cells. The patients, who were undergoing transplant as treatment for blood-related cancers or other disorders, all carried a CMV infection from earlier in life that had been wrestled into dormancy by their immune system. Twenty-four weeks after completing up to 14 weeks of treatment, 61 percent of the patients receiving a placebo had developed a CMV infection serious enough to require treatment or had discontinued the trial. By contrast, only 38 percent of those treated with letermovir developed that level of CMV infection or did not complete the trial.

Unlike other drugs able to forestall active CMV infection in stem cell transplant patients, letermovir did so without producing unacceptable toxicities. Most of the side effects associated with letermovir were tolerable, including mild cases of nausea or vomiting, and some swelling, investigators found. Letermovir also conferred a survival benefit: at the 24-week mark, 15 percent of the placebo patients had died, compared to 10 percent of those receiving letermovir.

‘For the first time, we seem to have a drug that is a true safe and effective preventive for CMV infection in stem cell transplant patients,’ said the study’s lead author, Francisco Marty, MD, an infectious disease specialist at Dana-Farber and BWH. ‘Letermovir will allow many patients to avoid infection, usually with no or mild side effects, and seems to provide a survival benefit in the first six months post-transplant.’

Dana Farber Cancer Institute