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Efficacy of prophylactic letermovir for cytomegalovirus reactivation in hematopoietic cell transplantation: a multicenter real-world data

Bone Marrow Transplantation volume 56, pages 853–862 (2021)Cite this article

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Abstract

A novel anti-cytomegalovirus (CMV) agent, letermovir (LMV), could reportedly improve the outcomes of allogeneic hematopoietic cell transplantation (allo-HCT) recipients because of its high potential to prevent CMV reactivation. Therefore, 685 Japanese allo-HCT recipients, of whom ~80% had a high risk of CMV reactivation, were retrospectively analyzed to assess the impacts of prophylactic LMV on the incidence of clinically significant CMV (csCMV) infection as well as their transplant outcome. By comparing 114 patients who received LMV prophylaxis for a median 92 days to 571 patients without prophylaxis, we observed that prophylactic LMV could significantly (1) reduce the 180-day cumulative incidence of csCMV infection (44.7 vs. 72.4%, p < 0.001), (2) delay the median time until initiation of CMV antigenemia-guided preemptive therapy (90 vs. 36 days, p < 0.001), (3) shorten the duration of anti-CMV preemptive treatment (21 vs. 25 days, p = 0.006), and (4) improve the overall survival rate at 180 days after transplant (80.4 vs. 73.0%, p = 0.033) with a trend of lower non-relapse mortality (8.9 vs. 14.9%, p = 0.052). Our findings demonstrate that prophylactic LMV treatment is highly effective in preventing the development of csCMV infection and ultimately reduces transplant-related mortality.

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Fig. 1: Prophylactic LMV could shorten the time of CMV treatment.
Fig. 2: Prophylactic LMV could reduce the incidence of CMV reactivation and/or CMV diseases.
Fig. 3: Forest plots indicating the hazard ratio of prophylactic LMV for csCMV infection among each subgroup.
Fig. 4: Prophylactic LMV could improve transplant outcome.

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Acknowledgements

The authors would like to thank the medical and nursing staff who cared for the patients at the Fukuoka Blood and Marrow Transplantation Group and provided patients information.

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Authors and Affiliations

  1. Department of Medicine and Biosystemic Science, Kyushu University Graduate School of Medical Science, Fukuoka, Japan

    Yasuo Mori, Fumiaki Jinnouchi, Katsuto Takenaka, Takuya Harada, Goichi Yoshimoto, Koji Kato, Koichi Akashi & Toshihiro Miyamoto

  2. Department of Hematology, Clinical Immunology, and Infectious Diseases, Ehime University Graduate School of Medicine, Ehime, Japan

    Katsuto Takenaka

  3. Department of Hematology, Harasanshin Hospital, Fukuoka, Japan

    Takatoshi Aoki & Tomohiko Kamimura

  4. Department of Hematology, Hamanomachi Hospital, Fukuoka, Japan

    Takuro Kuriyama, Hideho Henzan & Tetsuya Eto

  5. Department of Hematology and Clinical Research Institute, National Hospital Organization Kyushu Medical Center, Fukuoka, Japan

    Masanori Kadowaki & Ken Takase

  6. Department of Hematology, Imamura General Hospital, Kagoshima, Japan

    Jun Odawara & Yoshikiyo Ito

  7. Department of Internal Medicine, Kitakyushu Municipal Medical Center, Fukuoka, Japan

    Toshiyuki Ueno & Yuju Ohno

  8. Japan Community Health Care Organization (JCHO) Kyushu Hospital, Fukuoka, Japan

    Kentaro Kohno & Ryosuke Ogawa

  9. Division of Hematology/Oncology, Kurume University School of Medicine, Fukuoka, Japan

    Koji Nagafuji

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Correspondence to Toshihiro Miyamoto.

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Conflict of interest

KA received grants and honoraria from Kyowa Hakko Kirin Co., Ltd, Janssen Pharmaceutical K.K., Bristol-Myers Squibb Co., Ltd, Novartis Pharma K.K., Otsuka Pharmaceutical Co., Ltd, MSD Co., Ltd, Astellas Pharmaceutical Co., Ltd, Nippon Shinyaku Co., Ltd, Sumitomo Dainippon Pharmaceutical Co., Ltd, Celgene Co., Ltd, SymBio Pharmaceutical Co., Ltd, Daiichi Sankyo Pharmaceutical Co., Ltd, and Takeda Pharmaceutical Co., Ltd. KN and TM received honoraria from Bristol-Myers Squibb Co., Ltd, Otsuka Pharmaceutical Co., Ltd, MSD Co., Ltd, Astellas Pharmaceutical Co., Ltd, Astellas Amgen Pharmaceutical Co., Ltd, Celgene Co., Ltd, Abbvie Pharmaceutical Co., Ltd, Takeda Pharmaceutical Co. The other authors have no conflict of interests to declare.

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Mori, Y., Jinnouchi, F., Takenaka, K. et al. Efficacy of prophylactic letermovir for cytomegalovirus reactivation in hematopoietic cell transplantation: a multicenter real-world data. Bone Marrow Transplant 56, 853–862 (2021). https://doi.org/10.1038/s41409-020-01082-z

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