Among patients undergoing hematopoietic cell transplantation (HCT), prophylactic letermovir may delay cytomegalovirus (CMV)-specific cellular reconstitution, according to research published in Blood. Indicating patient T cell polyfunctionality may, furthermore, help to identify patients at risk of late CMV infection.

Previous research showed that letermovir decreases clinically significant CMV after HCT. There is, however, evidence that discontinuation of letermovir prophylaxis may increase the risk of significant CMV events, which may increase the risk of morbidity and mortality.

Furthermore, reduced cellular immunity to CMV at 3 months post-HCT is linked with increased mortality. A donor’s serostatus may also predict patient T cell reconstitution, indicating that donor-derived immunity is relevant to patient immune recovery.

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Combinatorial polyfunctionality analysis of antigen specific T cell subsets (COMPASS)—a novel tool for determining antigen-specific T cell responses—has the potential to help establish patient polyfunctional CMV-specific immunity. For this prospective cohort study, researchers used COMPASS to determine whether reduced CMV-specific cellular immunity is predictive of CMV reactivation post-HCT.

Data from 56 patients who received letermovir and 93 patient-controls were included. In the letermovir and control groups, the median age was 53.9 vs 53.2 years, respectively, 63% vs 60% of patients were male, and 71% vs 61% of patients had a donor with CMV-negative serostatus.

The researchers used flow cytometry to determine T cell response levels at 3 months post-HCT, using both CMV immediate early-1 (IE-1) and phosphoprotein 65 (pp65) antigens.

Among patients who received letermovir, the polyfunctional T cell responses to both IE-1 and pp65 were lower compared with the control group, regardless of donor CMV serostatus. Furthermore, in the letermovir group, the CMV shedding rate was linked with improved CD41 responses to IE-1, while greater DNAemia—the presence of CMV DNA in evaluated samples—and increased CMV shedding were both linked with CD81 responses to pp65.

“COMPASS effectively measures polyfunctional CMV-specific T-cell responses, however, larger studies are needed to evaluate its effectiveness and accuracy in predicting CMV events,” the authors wrote.

Disclosure: The study author(s) declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures. 


Zamora D, Duke ER, Xie H, et al. Cytomegalovirus-specific T-cell reconstitution following letermovir prophylaxis after hematopoietic cell transplantation. Blood. 2021;138(1):34-43. doi:10.1182/blood.2020009396