New Drug Prevents Viral Infections in Stem Cell Transplant Patients

Because bone marrow transplant patients have had their bone marrows wiped out with radiation or rather severe drugs, their immune systems tend to be kaput until the transplanted bone marrow stem cells start making new immune cells to reconstitute the immune system. Consequently, bone marrow transplant patients can contract a whole host of truly diabolical diseases.

One disease that shows up with some frequency in bone marrow transplant patients is cytomegalovirus (CMV) infections. CMV can cause pneumonia, diarrhea, digestive tract ulcers, and other problems. Some antiviral drugs do exist (ganciclovir, or its prodrug valganciclovir, foscarnet, and cidofovir), but they can cause kidney dysfunction or bone marrow suppression. Neither of these are desirable side effects. Clearly new drugs are needed (see Ahmed, A. Infect Disord Drug Targets. 2011 Oct;11(5):475-503).

A new clinical trial by researchers at Dana-Farber Cancer Institute and Brigham and Women’s Hospital has tested a drug called CMX001. When bone marrow transplant patients took it shortly after transplant, they were much less likely to contract CMV infections that those who did not take the drug.

The study’s lead author, Francisco Marty from Dana-Farber and Brigham and Women’s said: “With current agents, between 3 and 5 percent of allogeneic transplant patients develop CMV disease within six months of transplantation, and a small number of them die of it. There is clearly a need for better treatments with fewer adverse effects. This clinical trial examined whether the disease can be prevented, rather than waiting for blood tests to show that treatment is needed.”

By the time we become adults, most of use have been infected by CMV. However in most cases our immune systems hold it in check. In stem cell transplant patients, however, the immune system is replaced with those of a donor after receiving sizable doses of chemotherapy. During this period, long-dormant viruses, such as CMV, can reactivate and cause CMV disease. CMV is a type of herpes virus. Herpes viruses do a very good job of keeping a low profile and hiding in various types of cells. Only by treating with an effective anti-viral drug can CMV disease be thwarted.

In this Phase 2 clinical trial, 230 stem cell transplant recipients at 27 different centers across the United States were randomly assigned to either the oral CMX001 group to the placebo group. All patients took the drugs or placebos after their bone marrow transplant procedure and the drugs or placebos were taken for 9-11 weeks.

Those patients that took 100 milligrams of CMX001 twice a week, 10% had a CMV event in which CMV was detectable in the blood and the symptoms of CMV disease appeared. However, 37% of those patients who took the placebo had a CMV event. The most common side effect was diarrhea, which is no surprise given the fragile state of these patients.

“The results show the effectiveness of CMX001 in preventing CMV infections in this group of patients,” said Marty. “Because CMX001 is known to be active against other herpes viruses and against adenoviruses that sometimes affect transplant patients, it may be useful as a preventative or treatmentagent for those infections as well.”

See New England Journal of Medicine, 2013; 369(13): 1227.