By Marilynn Larkin
NEW YORK (Reuters Health) - Patients who underwent an allogeneic hematopoietic stem cell transplant (HCT) experienced fewer cytomegalovirus (CMV)-related complications after Triplex vaccine injections in a phase-2, randomized, placebo-controlled trial.
Triplex is a recombinant attenuated poxvirus (modified vaccinia Ankara) expressing immunodominant CMV antigens.
"Triplex...can replace the antiviral letermovir as a protective mechanism using the immune system to prevent CMV reactivation in susceptible transplant recipients," Dr. Don Diamond of City of Hope Comprehensive Cancer Center in Duarte, California, told Reuters Health by email. "The promise of this vaccine is that it helps reconstitute immunity to the virus, rather than suppressing immunity, as has been shown for many antivirals."
Dr. Diamond and colleagues enrolled 102 CMV-positive adults at high risk for CMV reactivation from three U.S. HCT centers. The median age was about 58; women made up 24% of the Triplex and 13% of the placebo groups.
Intramuscular injections of Triplex or placebo were given on days 28 and 56 after HCT.
As reported in Annals of Internal Medicine, all participants received the first injection, and 91 (89.2%) received both (46 Triplex and 45 placebo).
Levels of long-lasting, CMV pp65-specific T cells with effector memory phenotype (indicating potential antiviral activity) were significantly higher in Triplex than placebo recipients.
CMV reactivation occurred in five Triplex (9.8%) and 10 placebo (19.6%) recipients (hazard ratio, 0.46). No grade 3 or 4 adverse events related to vaccination were observed within two weeks after vaccination, and no Triplex recipient had serious adverse events or died of non-relapse causes during the first 100 days.
The incidence of severe acute graft-versus-host disease (GVHD) after injection was similar between groups.
Of note, the lower-than-expected incidence of CMV events in the placebo group reduced the power of the trial.
Dr. Diamond told Reuters Health by email, "The lower incidence of CMV reactivation in the placebo group is a result of our continued improvement in the treatment of patients. The three medical centers...involved in the study have some of the best outcome measures in the US, so it is not surprising that side effects such as CMV reactivation might be lower in that group."
"An additional reason for the lower level of reactivation in the placebo arm is some of our eligibility requirements, such that some of the sicker patients were not eligible for the study," he said. "Future studies, especially a phase 3 registration trial, will dispense with those requirements, which will likely cause an increase in the CMV reactivation rate globally and, hence, in the placebo arm of the trial."
"We fully expect that there will be control by the vaccine in the Triplex arm and have no concerns that it will distort future results," he added.
Dr. Samer Al-Homsi, director of the Blood and Marrow Transplant Program at NYU Langone Perlmutter Cancer Center in New York City, commented in an email to Reuters Health, "CMV reactivation and related complications represent a significant issue following donor blood and marrow transplantation. The currently available treatments are associated with non-negligible side-effects."
The current study "is a welcome advance," he said. "However, much remains to be learned about the effect of the vaccine in patients with GVHD and the impact of the vaccine on disease relapse and overall outcomes."
The study was funded in part by Helocyte, which is developing the vaccine. Dr. Diamond and a number of coauthors receive fees from the company.
SOURCE: https://bit.ly/2vYziBt Annals of Internal Medicine, online February 10, 2020.