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Coadministration of letermovir and sirolimus in allogeneic hematopoietic cell transplant recipients

Bone Marrow Transplantation volume 57, pages 128–130 (2022)Cite this article

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Cytomegalovirus (CMV) reactivation after allogeneic hematopoietic cell transplant (HCT) is a potentially deleterious infection, being historically associated with transplant-related morbidity and mortality (TRM) [1]. Guided by the strict surveillance of CMV-viremia, the introduction of pre-emptive antiviral treatment (PET) has shown to control viral infection, thus improving HCT outcomes [2]. However, anti-CMV drugs are often associated with major toxicities. Thus, the approval of the CMV-specific DNA-terminase inhibitor letermovir (LMV) for CMV prophylaxis represents a turning point in this scenario. In the registration study, clinically relevant CMV (CR-CMV) infection rate decreased from 44.3 to 18.9% by week 24 post-HCT in CMV-seropositive patients receiving LMV [3]. LMV prophylaxis has been investigated in several transplant platforms [4, 5]; however, given the known drug-to-drug interaction between LMV and calcineurin-inhibitors (CNI), LMV prophylaxis administration in a CNI-free setting is a topic of interest. Herein, we retrospectively investigated the safety and efficacy of LMV in preventing CR-CMV infection in a sirolimus-based HCT platform.

All patients transplanted in our institution who received LMV and sirolimus prophylaxis were included in the study. All patients have been treated according to current institutional guidelines, upon written informed consent for transplant procedures and the use of medical records for research. Starting from March 2019, LMV-based CMV prophylaxis has been routinely adopted in our bone marrow transplant (BMT) unit. Until July 2020, LMV has been given to all CMV-seropositive patients who were transplanted from unrelated donors, cord blood unit, mismatched related donors, and CMV-seronegative HLA-identical sibling donors; starting from August 2020, LMV has been routinely administered to all CMV-seropositive BMT recipients. Patients received 480 mg daily dose of LMV from transplant day (day0) until either day100, CR-CMV reactivation or major toxicity development, whichever came first.

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Data availability

The datasets generated for this study are available on request to the corresponding author.

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Author notes

  1. These authors contributed equally: Elisabetta Xue, Francesca Lorentino.

  2. These authors contributed equally: Maria Teresa Lupo Stanghellini, Raffaella Greco.

Authors and Affiliations

  1. Hematology and Bone Marrow Transplantation Unit, IRCCS San Raffaele Scientific Institute, Milan, Italy

    Elisabetta Xue, Francesca Lorentino, Daniela Clerici, Francesca Farina, Fabio Giglio, Edoardo Campodonico, Rosamaria Nitti, Massimo Bernardi, Consuelo Corti, Jacopo Peccatori, Fabio Ciceri, Maria Teresa Lupo Stanghellini & Raffaella Greco

  2. PhD Program in Public Health, Department of Medicine and Surgery, University of Milano-Bicocca, Milan, Italy

    Francesca Lorentino

  3. Clinic of Infectious Diseases, Division of Immunology, Transplantation and Infectious Diseases, IRCCS San Raffaele Scientific Institute, Milan, Italy

    Chiara Oltolini

  4. University Vita-Salute San Raffaele, Milan, Italy

    Edoardo Campodonico, Rosamaria Nitti & Fabio Ciceri

Authors
  1. Elisabetta Xue
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  2. Francesca Lorentino
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  3. Daniela Clerici
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  4. Francesca Farina
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  5. Chiara Oltolini
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  6. Fabio Giglio
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  7. Edoardo Campodonico
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  8. Rosamaria Nitti
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  9. Massimo Bernardi
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  10. Consuelo Corti
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  11. Jacopo Peccatori
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  12. Fabio Ciceri
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  13. Maria Teresa Lupo Stanghellini
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  14. Raffaella Greco
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Contributions

RG, MTLS, JP, EX, and FL designed the study. All authors contributed to patient clinical care and data collection. EX, FL, RG, and MTLS interpreted the data. FL performed statistical analysis. EX prepared the table. RG and MTLS provided scientific advice and supervision. EX, FL, RG, MTLS and JP wrote the manuscript. All authors have approved the final version of the manuscript.

Corresponding authors

Correspondence to Jacopo Peccatori or Raffaella Greco.

Ethics declarations

Competing interests

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Ethics approval and consent to participate

All patients were treated according to Institutional programs upon written informed consent for transplant procedures, use of medical records and immunological studies for patients undergoing allogeneic HSCT within the non-interventional “ALMON study”, approved by San Raffaele Institutional Ethical Committee in date 19/10/2007.

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Supplementary information

41409_2021_1486_MOESM1_ESM.docx

Supplementary Material for Coadministration of Letermovir and Sirolimus in Allogeneic Hematopoietic Cell Transplant Recipients

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Xue, E., Lorentino, F., Clerici, D. et al. Coadministration of letermovir and sirolimus in allogeneic hematopoietic cell transplant recipients. Bone Marrow Transplant 57, 128–130 (2022). https://doi.org/10.1038/s41409-021-01486-5

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