Cytomegalovirus prevention in thoracic organ transplantation: A single-center evaluation of letermovir prophylaxis

Saullo, Jennifer L.; Baker, Arthur W.; Snyder, Laurie D.; Reynolds, John M.; Zaffiri, Lorenzo; Eichenberger, Emily M.; Ferrari, Alana; Steinbrink, Julie M.; Maziarz, Eileen K.; Bacchus, Melissa; Berry, Holly; Kakoullis, Stylianos; Wolfe, Cameron R.

doi:10.1016/j.healun.2021.12.005

Cited by 21 publications

(32 citation statements)

References 23 publications

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“…Current reports of letermovir use in SOT have shown safety and efficacy but are largely limited to intra-abdominal and lung transplant recipients. [8][9][10][11] There is a paucity of research on letermovir for usage in HT patients.…”

Section: Discussionmentioning

confidence: 99%

“…While letermovir is currently approved for usage in allogeneic HSCT recipients, it does not have an indication in SOT recipients. Current reports of letermovir use in SOT have shown safety and efficacy but are largely limited to intra‐abdominal and lung transplant recipients 8–11 . There is a paucity of research on letermovir for usage in HT patients.…”

Section: Discussionmentioning

confidence: 99%

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Letermovir for cytomegalovirus prophylaxis in high‐risk heart transplant recipients

Golob

Batra

DeFilippis

et al. 2022

Clinical Transplantation

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Letermovir is a novel agent for the prevention of cytomegalovirus (CMV) infection and disease that, unlike traditional CMV DNA polymerase inhibitors, does not carry the risk of myelosuppression. The purpose of this study was to evaluate the safety, efficacy, and clinical application of letermovir for CMV prophylaxis in heart transplant (HT) recipients. Between November 1, 2019, and October 1, 2021, at a single, tertiary care hospital, 17 HT recipients were initiated on letermovir due to leukopenia while on valganciclovir. Fifteen (88%) had high-risk mismatch (CMV D+/R-). Median time on letermovir was 5 months (interquartile range, 2-8 months.) At the end of the study period, nine of 17 patients (52.9%) were still on letermovir and four of the 17 (23.5%) had successfully completed the prophylaxis window on letermovir and been switched to the pre-emptive strategy. One patient developed clinically significant CMV viremia in the setting of being unable to obtain medication due to insurance barriers but was later successfully restarted on letermovir. One patient was unable to tolerate letermovir due to symptoms of headache and myalgias. Two patients developed lowlevel non-clinically significant CMV viremia and were switched back to valacyclovir. All patients had tacrolimus dosages reduced at time of letermovir initiation to minimize the risk of supratherapeutic tacrolimus concentration. One patient required hospitalization due to symptomatic tacrolimus toxicity. For HT recipients who cannot tolerate valganciclovir, letermovir presents an alternative for CMV prophylaxis. Close monitoring for breakthrough CMV and calcineurin inhibitor levels is necessary. Larger studies are required to further delineate its use and help provide further evidence of its safety and efficacy.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Letermovir for cytomegalovirus prophylaxis in high‐risk heart transplant recipients

Golob

Batra

DeFilippis

et al. 2022

Clinical Transplantation

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“…In this study cohort, G‐CSF was especially utilized for patients with concomitant neutropenia to shorten the duration of leukopenia and can help facilitate more rapid reintroduction of medications. Letermovir, a novel antiviral prophylactic agent without myelosuppressive properties, can also be useful in patients at high risk for CMV infection and prone to leukopenia 11 …”

Section: Discussionmentioning

confidence: 99%

Early post‐transplant leukopenia in heart transplant recipients and its impact on outcomes

Batra

DeFilippis

Golob

et al. 2023

Clinical Transplantation

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Background: Leukopenia in the early period following heart transplantation (HT) is not well-studied. The aim of this study was to evaluate risk factors for the development of post-transplant leukopenia and its consequences for HT recipients.Methods: Adult patients at a large-volume transplant center who received HT between January 1, 2010 and December 31, 2020 were included. The incidence of leukopenia (WBC ≤3 × 10 3 /µL) in the first 90-days following HT, individual risk factors, and its effect on 1-year outcomes were evaluated.Results: Of 506 HT recipients, 184 (36%) developed leukopenia within 90-days.Median duration of the first leukopenia episode was 15.5 days (IQR 8-42.5 days). Individuals who developed leukopenia had lower pre-transplant WBC counts compared to those who did not (6.1 × 10 3 /µL vs. 6.9 × 10 3 /µL, p = .02). Initial immunosuppressive and infectious chemoprophylactic regimens were not significantly different between groups. Early leukopenia was associated with a higher mortality at 1-year (6.6% vs. 2.1%, p = .008; adjusted HR 3.0) and an increased risk of recurrent episodes. Rates of infection and rejection were not significantly different between the two groups.Conclusions: Leukopenia in the early period following HT is common and associated with an increased risk of mortality. Further study is needed to identify individuals at highest risk for leukopenia prior to transplant and optimize immunosuppressive and infectious chemoprophylactic regimens for this subgroup.

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“…At present, other antiviral treatments against CMV have proven to be useful in prophylaxis with fewer side effects. Letermovir, a drug approved for CMV-prophylaxis of bone marrow transplantation, has been shown to be beneficial in lung transplantation with fewer adverse effects in some case series [ 35 , 36 , 37 , 38 , 39 , 40 ]. Recently, Maribavir has been shown in a phase 3 clinical trial to be useful in infections refractory to conventional treatment, with less neutropenia and less renal failure [ 41 ].…”

Section: Discussionmentioning

confidence: 99%

Evaluation of Two Different CMV-Immunoglobulin Regimens for Combined CMV Prophylaxis in High-Risk Patients following Lung Transplant

et al. 2022

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Background: The clinical benefits of the common off-label use of cytomegalovirus (CMV)-specific immunoglobulin (CMV-Ig) combined with antivirals in organ transplantation have not been previously assessed. The objective was to compare the risk of CMV infection and other post-transplantation outcomes between two CMV-Ig prophylaxis regimens in lung transplant recipients; Methods: Retrospective study of 124 donor CMV positive/recipient negative (D+/R–) patients receiving preventive ganciclovir/valganciclovir for 12 months, of whom 62 received adjunctive CMV-Ig as per label indication (short regimen [SR-Ig]; i.e., 7 doses over 2.5 months) and were compared to 62 who received an extended off-label regimen (ER-Ig) consisting of 17 doses over one year after transplantation. Results: The incidence of CMV infection or disease, acute rejection, chronic lung allograft dysfunction, and survival did not differ between the two CMV-Ig schedules. Although the time to the first CMV infection after transplantation was shorter in the ER-Ig than in the SR-Ig adjunctive group (log-rank: p = 0.002), the risk was independently predicted by antiviral cessation (odds ratio = 3.74; 95% confidence interval = 1.04–13.51; p = 0.030), whereas the CMV-Ig schedule had no effect. Conclusions: Extending the adjunctive CMV-Ig prophylaxis beyond the manufacturer’s recommendations up to one year does not confer additional clinical benefits regarding lung post-transplantation outcomes.

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Cytomegalovirus prevention in thoracic organ transplantation: A single-center evaluation of letermovir prophylaxis

Cited by 21 publications

References 23 publications

Letermovir for cytomegalovirus prophylaxis in high‐risk heart transplant recipients

Letermovir for cytomegalovirus prophylaxis in high‐risk heart transplant recipients

Early post‐transplant leukopenia in heart transplant recipients and its impact on outcomes

Evaluation of Two Different CMV-Immunoglobulin Regimens for Combined CMV Prophylaxis in High-Risk Patients following Lung Transplant

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