Letermovir reduces clinically significant cytomegalovirus reactivation after allogeneic HSCT
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Letermovir reduced clinically significant cytomegalovirus reactivation among patients who underwent allogeneic hematopoietic stem cell transplant, according to retrospective results presented at TCT Meetings Digital Experience.
Rates of late cytomegalovirus reactivation appeared high among patients who did not receive letermovir (Prevymis, Merck) prophylaxis, Jaime Shahan, MPAS, PA-C, physician assistant in the bone marrow transplant and hematologic malignancies clinic at UT Southwestern Harold C. Simmons Comprehensive Cancer Center, and colleagues found.
Cytomegalovirus-specific T-cell immunity may be a useful tool to guide decision-making about letermovir discontinuation after transplant for at-risk patients, they added.
Cytomegalovirus is a common complication among patients who undergo allogeneic HSCT. Reactivation has been linked to a variety of complications after transplant, including acute and chronic graft-versus-host disease, graft failure, multiorgan failure, bacterial and fungal infections, and higher mortality risk.
The antiviral drug letermovir is approved for prophylaxis among adult allogeneic HSCT recipients who are cytomegalovirus seropositive through day 100. Although the agent has reduced incidence of cytomegalovirus reactivation, late reactivation — defined as after day 100 — has been reported after discontinuation of the agent.
Risk for late reactivation is highest among patients with impaired cytomegalovirus-specific T-cell immunity, due either to effects of the conditioning regimen or immunosuppressives, according to study background.
Shahan and colleagues hypothesized that cytomegalovirus-specific T-cell immunity could be used to help determine optimal timing of letermovir discontinuation.
Researchers reviewed data of 26 cytomegalovirus-positive allogeneic HSCT recipients who received letermovir prophylaxis between July 2019 and October 2020.
They compared outcomes in this group with those of 33 patients who underwent allogeneic HSCT between March 2018 and June 2019 and did not receive letermovir prophylaxis.
A comparable percentage of patients in the prophylaxis and no-prophylaxis groups had cytomegalovirus recipient-positive/donor-positive status (54% vs. 54.5%). All other patients were recipient-positive/donor-negative.
Investigators used polymerase chain reaction testing to compare rates of clinically significant cytomegalovirus reactivation — defined as cytomegalovirus viremia that required preemptive treatment — as well as late reactivation between groups.
Researchers also used whole blood testing stimulated with cytomegalovirus antigens and stained for surface markers to monitor cytomegalovirus T-cell immunity in a subgroup of patients.
They correlated CD4-count monitoring with cytomegalovirus T-cell immunity and used results of these tests to inform decisions about timing of letermovir discontinuation.
Researchers reported a lower rate of clinically significant cytomegalovirus reactivation in the letermovir prophylaxis group (3.8% vs. 60.6%; P < .001). Late cytomegalovirus reactivation also was less common in the letermovir group but the difference did not reach statistical significance (3.8% vs. 15.2%). All patients in the letermovir group who developed late reactivation did so after stopping the drug.
Five patients (19.2%) who received letermovir discontinued the agent due to potential toxicity.
Researchers monitored 15 patients in the letermovir group for cytomegalovirus T-cell immunity. Ten (66.6%) recovered their immunity by data cutoff. Median time to recovery was 141 days (range, 97-195) after transplant, with five patients recovering by about day 100. One (10%) of the patents who recovered T-cell immunity after letermovir discontinuation developed late cytomegalovirus reactivation.
“We do think our findings need to be validated in a larger cohort because we did have a really small number of patients on our study,” Shahan said during a presentation.
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Shahan JL, et al. Abstract 102. Presented at: The 2021 TCT Meetings Digital Experience (virtual meeting); Feb. 8-12, 2021.
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