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Letermovir reduces cytomegalovirus in HLA-matched and mismatched allogeneic hematopoietic cell transplant patients receiving post-transplant cyclophosphamide

Bone Marrow Transplantation volume 60, pages 1383–1386 (2025)Cite this article

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Cytomegalovirus (CMV) is a common infection in allogeneic hematopoietic cell transplant (HCT) patients and is associated with worse non-relapse mortality (NRM) and overall survival (OS) [1]. Risk factors include patient/donor CMV serostatus, T-cell depletion for graft-versus-host disease (GVHD) prophylaxis or human leukocyte antigen (HLA) mismatched donors [2, 3]. Post-transplant cyclophosphamide (PTCy) is a standard GVHD prevention platform in allogeneic HCT; however, the impairment of T-cell function results in slower immune reconstitution and higher rates of infections [2, 4,5,6,7]. Thus, PTCy recipients face a higher risk of CMV infection compared to calcineurin (CNI)-based regimens [2,3,4,5]. Letermovir, a CMV terminase complex inhibitor, demonstrated efficacy in reducing CMV in allogeneic HCT recipients [8]. We evaluated the impact of letermovir on clinically significant CMV infection (csCMVi) in allogeneic HCT patients receiving PTCy-based GVHD prophylaxis.

This retrospective study included consecutive adult patients undergoing allogeneic HCT with PTCy for a hematologic malignancy at Moffitt Cancer Center from 2014-2022. Myeloablative (MAC) and reduced intensity (RIC) conditioning regimens were included. Donors included matched sibling (MSD), matched unrelated (MUD), mismatched unrelated (MMUD), and haploidentical. Exclusions included umbilical cord blood (UCB) transplant, prior allogeneic HCT, or receipt of anti-thymocyte globulin (ATG) or alemtuzumab. Demographic and clinical data were obtained from the Moffitt Blood and Marrow Transplant Research and Analysis Information network (BRAIN) database and manual chart review.

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Fig. 1: Cytomegalovirus (CMV) related outcomes according to CMV serostatus and letermovir use.

Data availability

The data supportive the findings of this study are available upon reasonable request from the corresponding author.

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Acknowledgements

We thank the editorial assistance provided by the Moffitt Cancer Center’s Office of Scientific Publishing by Daley White and Gerard Hebert; no compensation was given beyond their regular salaries. This study was not endorsed by a research grant.

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Authors and Affiliations

  1. Department of Blood and Marrow Transplantation and Cellular Immunotherapy, Moffitt Cancer Center, Tampa, FL, USA

    Jena Schmitz, Eric Gaskill, Samantha Price, Rawan Faramand, Asmita Mishra, Lia Perez, Farhad Khimani, Aleksandr Lazaryan, Jose L. Ochoa-Bayona, Hien Liu, Abu-Sayeef Mirza, Michael Nieder, Claudio Anasetti, Taiga Nishihori, Joseph A. Pidala, Nelli Bejanyan & Hany Elmariah

  2. Department of Biostatistics and Bioinformatics, Moffitt Cancer Center, Tampa, FL, USA

    Biwei Cao & Jongphil Kim

  3. Department of Infectious Diseases, Moffitt Cancer Center, Tampa, FL, USA

    Aliyah Baluch & Olga Klinkova

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  1. Jena Schmitz
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Contributions

JS and HE designed the study, developed IRB approved protocol, collected data, reviewed the statistical analysis, interpreted the data, and wrote the manuscript. EG and SP collected data and contributed to the manuscript editing. BC and JK analyzed data and performed the statistical analysis. AB, OK, RF, AM, LP, FK, AL, JO, HL, SM, MN, CA, TN, JP, and NB reviewed the manuscript, provided feedback, and approved the final version.

Corresponding author

Correspondence to Hany Elmariah.

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Competing interests

RF is a member of the advisory board for Kite/Gilead and Autolus; receives research funding from Novartis and Orca Bio; and provides consultancy and honoraria for Sanofi. AM receives research funding from Novartis and Jannsen. AL provides consultancy, receives Honoria, and is a member of the scientific advisory board for Sanofi. HL provides consultancy and honoraria for BioLineRX. SM is on the Speakers Bureau for BMS. TN is on the advisory committee for Medexus; provides consultancy for ImmunoGen; receives research funding from Novartis; and receives personal fees from Karyopharm outside the submitted work. JP provides consultancy and serves on the advisory board/research support for Syndax, CTI Biopharma, Amgen, Regeneron, Incyte, and Sanofi; and receives research support from Novartis, Takeda, Janssen, Johnson and Johnson, Abbvie, and BMS. NB receives research funding from CRISPR; and provides consultancy for CareDX, ORCA Biosystem, AlloVir, Pfizer, and Anthem Bone Marrow/Stem Cell/Cellular Therapy NTQRC. HE receives research funding from BMS and provides consultancy for Shoreline Biosciences. The remainder of the authors have no conflicts of interest to disclose.

Ethics approval and consent to participate

This study was approved by the Moffitt Cancer Center Scientific Review Committee and the University of South Florida Institutional Review Board under Advarra protocol number Pro000064701. The study followed the guidelines set forth in the Declaration of Helsinki. The authors confirm the accuracy of the reported data, analyses, and adherence to the approved study protocol. Data were obtained from the BRAIN database, for which patients provided informed consent prior to transplant, including consent for inclusion in the database.

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Schmitz, J., Gaskill, E., Price, S. et al. Letermovir reduces cytomegalovirus in HLA-matched and mismatched allogeneic hematopoietic cell transplant patients receiving post-transplant cyclophosphamide. Bone Marrow Transplant 60, 1383–1386 (2025). https://doi.org/10.1038/s41409-025-02670-7

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