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Optimal Strategy for CMV Prevention in HCT

CE / CME

Reducing the Burden of Cytomegalovirus in HCT: Optimal Strategy for Prevention

Physician Assistants/Physician Associates: 1.00 AAPA Category 1 CME credit

Nurse Practitioners: 1.00 Nursing contact hours, includes 1.00 hour of pharmacotherapy credit

Released: July 21, 2023

Expiration: July 20, 2024

Roy F. Chemaly
Roy F. Chemaly, MD, MPH
CME/CE Information

Activity

Progress
1
Course Completed

On the Horizon

Vaccine research is an area of intense interest in CMV prevention. Following a prior history of unsuccessful vaccine trials in HCT patients, several promising candidates have reported results. One is an mRNA-based CMV vaccine (mRNA-1647), studied to date in a randomized, placebo-controlled phase II  study in healthy adults. Seronegative or seropositive individuals were included, with efficacy endpoints including development of antigen-specific antibodies and neutralizing titers. In the study, mRNA-11647 was immunogenic in CMV-seronegative individuals, causing a robust antibody response, and boosting neutralizing antibody titers in seropositive individuals. The vaccine was well-tolerated and is moving to phase III development.37 Another vaccine candidate using a modified vaccinia Ankara vector (Triplex) to develop CMV-specific T-cell response was studied in a phase II trial that enrolled 102 CMV-seronegative HCT recipients. Vaccination reduced the rate of CMV reactivation vs placebo, 9.8% vs 19.6%, respectively. The vaccine was safe, with no grade ≥3 toxicities.5,10 A phase I trial of Triplex vaccinated healthy matched related donors prior to HCT, of whom 16 of 17 were CMV seropositive prior to vaccination. The strategy led to early and robust CMV-specific T-cell reconstitution in recipients, all of whom were CMV seropositive. Vaccination was well tolerated. The study is now ongoing in phase II (NCT03560752).38 

A complex procedure called adoptive T-cell therapy or adoptive immunotherapy involves generating CMV-specific T-cells, then expanding them either in vitro or by infusing them into the transplant recipient. The process has been evaluated in several small studies, which suggest it is an effective approach to prophylaxis.2 However, it is still investigational and likely will be reserved for resistant or refractory CMV infection if it becomes available.2,7

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