Infectious Disease

Letermovir reduces the clinically vital reactivation of cytomegalovirus after allogeneic HSCT

February 14, 2021

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Shahan JL et al. Abstract 102. Presented at: The 2021 TCT Meetings Digital Experience (virtual meeting); February 8-12, 2021.

Disclosure:
Shahan does not report any relevant financial information. In the summary you will find all relevant financial information for all other researchers.

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Letermovir reduced clinically significant reactivation of cytomegalovirus in patients who had undergone allogeneic hematopoietic stem cell transplantation, according to retrospective results presented at the TCT Meetings Digital Experience.

The rates of late reactivation of the cytomegalovirus were high in patients not receiving letermovir prophylaxis (Prevymis, Merck). Jaime Shahan, MPAS, PA-C, Medical Assistant at the Bone Marrow Transplant and Hematologic Malignancy Clinic at UT Southwestern Harold C. Simmons Comprehensive Cancer Center and colleagues.

Infographic showing clinically significant cytomegalovirus reactivation rates

Cytomegalovirus-specific T-cell immunity could be a useful tool to guide decision-making about discontinuing letermovir after transplantation in patients at risk.

Cytomegalovirus is a common complication in patients undergoing allogeneic HSCT. Reactivation has been linked to a variety of post-transplant complications, including acute and chronic graft-versus-host disease, graft failure, multiple organ failure, bacterial and fungal infections, and an increased risk of mortality.

Jaime Shahan, MPAS, PA-C

Jaime Shahan

The antiviral drug letermovir is approved for prophylaxis in adult allogeneic HSCT recipients who are seropositive for cytomegalovirus up to day 100. Although the agent reduced the incidence of cytomegalovirus reactivation, late reactivation – defined as after day 100 – has been reported after discontinuation of the agent.

The risk of late reactivation is highest in patients with impaired cytomegalovirus-specific T-cell immunity, either due to the effects of the conditioning regimen or immunosuppressive drugs, depending on the study background.

Shahan and colleagues hypothesized that cytomegalovirus-specific T cell immunity could be used to determine the optimal time to discontinue letermovir.

The researchers reviewed data from 26 cytomegalovirus-positive allogeneic HSCT recipients who received letermovir prophylaxis between July 2019 and October 2020.

They compared the results in this group with those of 33 patients who had allogeneic HSCT performed between March 2018 and June 2019 and who were not receiving letermovir prophylaxis.

A comparable percentage of patients in the prophylactic and non-prophylactic groups had cytomegalovirus recipient-positive / donor-positive status (54% versus 54.5%). All other patients were recipient positive / donor negative.

Researchers used polymerase chain reaction tests to compare rates of clinically significant reactivation of cytomegalovirus – defined as cytomegalovirus viraemia that required preventive treatment – and late reactivation between groups.

Researchers also used whole blood tests stimulated with cytomegalovirus antigens and stained for surface markers to monitor cytomegalovirus T cell immunity in a subset of patients.

They correlated monitoring of CD4 counts with T cell immunity to cytomegalovirus, and used the results of these tests to make decisions about when to stop taking letermovir.

The researchers reported a lower rate of clinically significant reactivations of cytomegalovirus in the letermovir prophylaxis group (3.8% versus 60.6%; P <0.001). Late reactivation of cytomegalovirus was also less common in the letermovir group, but the difference did not reach statistical significance (3.8% versus 15.2%). All patients in the letermovir group who developed late reactivation did so after drug discontinuation.

Five patients (19.2%) who received letermovir discontinued the drug because of possible toxicity.

The researchers monitored 15 patients in the letermovir group for cytomegalovirus T cell immunity. Ten (66.6%) restored their immunity by disrupting data. The 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 that regained T-cell immunity after discontinuation of letermovir developed late reactivation of cytomegalovirus.

“We believe that our results need to be validated in a larger cohort as we only had a very small number of patients in our study,” Shahan said during a presentation.

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TCT |  Meeting on transplantation and cell therapy

TCT | Meeting on transplantation and cell therapy

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