Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2024 Oct;26(5):e14337.
doi: 10.1111/tid.14337. Epub 2024 Jul 9.

Use of letermovir for cytomegalovirus primary prophylaxis in lung transplant recipients

Hanna L Kleiboeker  1 , Jacob Wang  2 , Nicole Borkowski  3 , Brad Miner  3 , Alyson Prom  1 , Krista Paplaczyk  1 , Jennifer Wright  3 , Mrinalini Venkata Subramani  4 , Ambalavanan Arunachalam  4 , Alan D Betensley  4 , Rade Tomic  4 , Catherine N Myers  4
Affiliations

Use of letermovir for cytomegalovirus primary prophylaxis in lung transplant recipients

Hanna L Kleiboeker et al. Transpl Infect Dis. 2024 Oct.

Abstract

Background: Cytomegalovirus (CMV) is a driver of negative outcomes after lung transplant (LTX) and primary prophylaxis (PPX) with valganciclovir (VGC) is standard-of-care. VGC is associated with myelosuppression, prompting interest in letermovir (LTV).

Methods: Adults receiving LTX between April 1, 2015, and July 30, 2022, at our institution were evaluated. Patients were excluded if low CMV risk (D-/R-), survived <90 days post-LTX, or transferred care before PPX withdrawal. Primary outcomes were leukopenia (white blood cell count [WBC] ≤ 3.0 × 109/L), severe leukopenia (WBC ≤ 2.0 × 109/L), and neutropenia (absolute neutrophil count ≤ 1500 cells/µL) requiring granulocyte-colony stimulating factor (GCSF) on PPX. Secondary outcomes included breakthrough CMV infection and post-PPX CMV infection.

Results: 204 patients met inclusion criteria: 175 patients on VGC and 29 patients on LTV (after VGC conversion). Most patients received bilateral LTX (62.7%) with non-lymphocyte-depleting induction (96.6%) and moderate-risk serostatus (D+/R+, 48.5%). Patients transitioned from VGC to LTV after a mean of 178 days (SD 80.8 days) post-transplant. Patients on VGC experienced significantly more leukopenia (82.3% vs. 58.6%, p = 0.008), severe leukopenia (57.1% vs. 31.0%, p = 0.016), and neutropenia requiring GCSF (70.9% vs. 51.7%, p = 0.048). Breakthrough (5.7% vs. 3.4%, p = 0.955) and post-PPX (24.6% vs. 37.9%, p = 0.199) infections were similar. A subgroup analysis of patients with high-risk serostatus showed similar trends, though did not reach statistical significance.

Conclusions: In this single-center study, the incidence of leukopenia and neutropenia requiring GCSF were reduced with LTV compared to VGC. Breakthrough and post-PPX infections were not significantly different. This evidence suggests that LTV has comparable efficacy with reduced myelosuppression compared to VGC in LTX recipients, and may be an appropriate alternative for PPX.

Keywords: cytomegalovirus; lung transplant; myelosuppression; solid organ transplant.

PubMed Disclaimer

References

REFERENCES

    1. Beam E, Lesnick T, Kremers W, Kennedy CC, Razonable RR. Cytomegalovirus disease is associated with higher all‐cause mortality after lung transplantation despite extended antiviral prophylaxis. Clin Transplant. 2016;30(3):270‐278.
    1. Paraskeva M, Bailey M, Levvey BJ, et al. Cytomegalovirus replication within the lung allograft is associated with bronchiolitis obliterans syndrome. Am J Transplant. 2011;11(10):2190‐2196. https://doi.org/10.1111/j.1600‐6143.2011.03663.x Epub 2011 Jul 27 PMID: 21794087
    1. Snyder LD, Finlen‐Copeland CA, Turbyfill WJ, Howell D, Willner DA, Palmer SM. Cytomegalovirus pneumonitis is a risk for bronchiolitis obliterans syndrome in lung transplantation. Am J Respir Crit Care Med. 2010;181(12):1391‐1396. https://doi.org/10.1164/rccm.200911‐1786OC Epub 2010 Feb 18 PMID: 20167845; PMCID: PMC2894412
    1. Bennett D, Bergantini L, Ferrara P, et al. Cytomegalovirus infection is associated with development of chronic lung allograft dysfunction. Lung. 2022;200(4):513‐522.
    1. Kotton CN, Kumar D, Caliendo AM, et al. The third international consensus guidelines on the management of cytomegalovirus in solid‐organ transplantation. Transplantation. 2018;102(6):900‐931. https://doi.org/10.1097/TP.0000000000002191 PMID: 29596116

MeSH terms