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. 2024 Dec;38(12):e70033.
doi: 10.1111/ctr.70033.

Impact of Letermovir for Cytomegalovirus Primary Prophylaxis on Myelosuppression and Immunosuppression in Lung Transplant Recipients

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

Impact of Letermovir for Cytomegalovirus Primary Prophylaxis on Myelosuppression and Immunosuppression in Lung Transplant Recipients

Hanna L Kleiboeker et al. Clin Transplant. 2024 Dec.

Abstract

Background: Cytomegalovirus (CMV) is associated with detrimental outcomes after lung transplantation (LTX); primary prophylaxis (PPX) with valganciclovir (VGC) is guideline-recommended. VGC is associated with myelosuppression, spurring interest in letermovir (LTV).

Methods: Adults undergoing LTX between January 1, 2021, and July 30, 2022 at our institution who were converted from VGC to LTV for PPX were evaluated. Outcomes included antimetabolite dosing during PPX, the incidence and frequency of myelosuppressive events, and the time to the first myelosuppressive event.

Results: Twenty-nine LTX recipients met the inclusion criteria. Most patients received non-lymphocyte-depleting induction (96.6%) and had moderate risk CMV serostatus (D+/R+, 48.3%). Patients transitioned from VGC to LTV 177 days (IQR 102 days) post-transplant. After conversion to LTV, patients tolerated higher daily doses of mycophenolate (721 mg vs. 1000 mg, p = 0.008) or azathioprine (33.3 mg vs. 62.5 mg, p = 0.478). The incidence of myelosuppressive events was reduced (100.0% vs. 62.1%, p < 0.001) including leukopenia (96.6% vs. 58.6%, p = 0.001), severe leukopenia (82.8% vs 31.0%, p < 0.001) and neutropenia requiring GCSF (96.6% vs. 48.3%, p < 0.001) while on VGC compared to LTV. While on LTV, patients had a reduced rate of myelosuppressive events compared to VGC (1 event per 6.2 patient days vs. 1 event per 14.7 patient days, p < 0.001). While on LTV, one patient had breakthrough viremia (3.4%) that was treated with (val)ganciclovir.

Conclusions: In this single-center study, patients tolerated higher doses of antimetabolite immunosuppression, and the incidence and frequency of myelosuppressive events were reduced while on LTV compared to VGC. This evidence expands upon the current literature demonstrating improved tolerability of LTV in LTX recipients.

Keywords: cytomegalovirus; immunosuppression; lung transplant.

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References

    1. E. Beam, T. Lesnick, W. Kremers, C. C. Kennedy, and R. R. Razonable, “Cytomegalovirus Disease Is Associated With Higher All‐Cause Mortality After Lung Transplantation Despite Extended Antiviral Prophylaxis,” Clinical Transplantation 30, no. 3 (2016): 270–278.
    1. M. Paraskeva, M. Bailey, B. J. Levvey, et al., “Cytomegalovirus Replication Within the Lung Allograft Is Associated With Bronchiolitis Obliterans Syndrome,” American Journal of Transplantation 11, no. 10 (2011): 2190–2196, https://doi.org/10.1111/j.1600‐6143.2011.03663.x.
    1. L. D. Snyder, C. A. Finlen‐Copeland, W. J. Turbyfill, D. Howell, D. A. Willner, and S. M. Palmer, “Cytomegalovirus Pneumonitis Is a Risk for Bronchiolitis Obliterans Syndrome in Lung Transplantation,” American Journal of Respiratory and Critical Care Medicine 181, no. 12 (2010): 1391–1396, https://doi.org/10.1164/rccm.200911‐1786OC.
    1. D. Bennett, L. Bergantini, P. Ferrara, et al., “Cytomegalovirus Infection Is Associated With Development of Chronic Lung Allograft Dysfunction,” Lung 200, no. 4 (2022): 513–522.
    1. C. N. Kotton, D. Kumar, A. M. Caliendo, et al., The Transplantation Society International CMV Consensus Group, “The Third International Consensus Guidelines on the Management of Cytomegalovirus in Solid‐Organ Transplantation,” Transplantation 102, no. 6 (2018): 900–931, https://doi.org/10.1097/TP.0000000000002191.

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