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Impact of daratumumab on the development of engraftment syndrome after autologous peripheral blood stem cell transplantation for multiple myeloma

Bone Marrow Transplantation volume 60, pages 743–745 (2025)Cite this article

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The addition of daratumumab to induction, consolidation, and maintenance regimens confers significant benefits in progression-free survival (PFS) of patients with newly diagnosed transplantation-eligible multiple myeloma (MM) [1,2,3]. However, the association between the administration of daratumumab before autologous peripheral blood stem cell transplantation (ASCT) and ASCT-associated adverse events in patients with MM remains unclear. Conversely, engraftment syndrome (ES) is characterized by a continuum of peri-engraftment complications after ASCT, including fever, diarrhea, rash, pulmonary infiltrates, and liver dysfunction [4]. Various factors associated with the onset of ES have been investigated [5]. The present study aimed to identify risk factors for ES after ASCT in patients with MM, focusing on daratumumab before ASCT.

We analyzed consecutive patients who received ASCT for MM from May 2013 to December 2023 at Jichi Medical University to determine the incidence of ES. ES, determined using the Spitzer [6] and Maiolino [7] criteria, was diagnosed upon fulfillment of at least one of the conditions. Both definitions indicate the timing of ES onset as during the peri-engraftment period, which was up to 3 days before and 10 days after the day of neutrophil engraftment [5, 8]. The day of neutrophil engraftment was considered to be the first of three consecutive days with an absolute neutrophil count of >0.5 × 109/L. Per institutional policy, most patients received four 4-week courses of induction therapy with a bortezomib-based regimen. Since 2019, we have routinely administered bortezomib-lenalidomide-dexamethasone as the initial induction regimen. Patients who did not achieve measurable residual disease negativity by SRL-Flow [9] at the end of the first induction therapy received 2–4 courses of additional induction therapy consisting of daratumumab-based therapy as second induction therapy. Thereafter, peripheral blood stem cells were mobilized and collected after treatment with granulocyte-colony stimulating factor (G-CSF), which was administered alone or in combination with plerixafor. Patients received melphalan of 200 mg/m2, administered intravenously in equally divided doses on two consecutive days (days −3 and −2). The melphalan dose was reduced to 140 mg/m2 in patients with serum creatinine of >2.0 mg/dL. G-CSF was administered subcutaneously from day seven after ASCT. All statistical analyses were conducted with EZR [10].

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Data availability

We confirm that the data supporting the findings of this study are available within the article and its supplemental material.

References

  1. Moreau P, Attal M, Hulin C, Arnulf B, Belhadj K, Benboubker L, et al. Bortezomib, thalidomide, and dexamethasone with or without daratumumab before and after autologous stem-cell transplantation for newly diagnosed multiple myeloma (CASSIOPEIA): a randomised, open-label, phase 3 study. Lancet. 2019;394:29–38. https://doi.org/10.1016/S0140-6736(19)31240-1.

    Article  CAS  PubMed  Google Scholar 

  2. Voorhees PM, Kaufman JL, Laubach J, Sborov DW, Reeves B, Rodriguez C, et al. Daratumumab, lenalidomide, bortezomib, and dexamethasone for transplant-eligible newly diagnosed multiple myeloma: the GRIFFIN trial. Blood. 2020;136:936–45. https://doi.org/10.1182/blood.2020005288.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Sonneveld P, Dimopoulos MA, Boccadoro M, Quach H, Ho PJ, Beksac M, et al. Daratumumab, Bortezomib, Lenalidomide, and Dexamethasone for Multiple Myeloma. N Engl J Med. 2024;390:301–13. https://doi.org/10.1056/NEJMoa2312054.

    Article  CAS  PubMed  Google Scholar 

  4. Lee CK, Gingrich RD, Hohl RJ, Ajram KA. Engraftment syndrome in autologous bone marrow and peripheral stem cell transplantation. Bone Marrow Transpl. 1995;16:175–82.

    CAS  Google Scholar 

  5. Cornell RF, Hari P, Drobyski WR. Engraftment syndrome after autologous stem cell transplantation: an update unifying the definition and management approach. Biol Blood Marrow Transpl. 2015;21:2061–8. https://doi.org/10.1016/j.bbmt.2015.08.030.

    Article  Google Scholar 

  6. Spitzer TR. Engraftment syndrome following hematopoietic stem cell transplantation. Bone Marrow Transpl. 2001;27:893–8. https://doi.org/10.1038/sj.bmt.1703015.

    Article  CAS  Google Scholar 

  7. Maiolino A, Biasoli I, Lima J, Portugal AC, Pulcheri W, Nucci M. Engraftment syndrome following autologous hematopoietic stem cell transplantation: definition of diagnostic criteria. Bone Marrow Transpl. 2003;31:393–7. https://doi.org/10.1038/sj.bmt.1703855.

    Article  CAS  Google Scholar 

  8. Cornell RF, Hari P, Zhang MJ, Zhong X, Thompson J, Fenske TS, et al. Divergent effects of novel immunomodulatory agents and cyclophosphamide on the risk of engraftment syndrome after autologous peripheral blood stem cell transplantation for multiple myeloma. Biol Blood Marrow Transpl. 2013;19:1368–73. https://doi.org/10.1016/j.bbmt.2013.06.017.

    Article  CAS  Google Scholar 

  9. Takamatsu H, Yoroidaka T, Fujisawa M, Kobori K, Hanawa M, Yamashita T, et al. Comparison of minimal residual disease detection in multiple myeloma by SRL 8-color single-tube and EuroFlow 8-color 2-tube multiparameter flow cytometry. Int J Hematol. 2019;109:377–81. https://doi.org/10.1007/s12185-019-02615-z.

    Article  CAS  PubMed  Google Scholar 

  10. Kanda Y. Investigation of the freely available easy-to-use software ‘EZR’ for medical statistics. Bone Marrow Transpl. 2013;48:452–8. https://doi.org/10.1038/bmt.2012.244.

    Article  CAS  Google Scholar 

  11. Krejcik J, Casneuf T, Nijhof IS, Verbist B, Bald J, Plesner T, et al. Daratumumab depletes CD38+ immune regulatory cells, promotes T-cell expansion, and skews T-cell repertoire in multiple myeloma. Blood. 2016;128:384–94. https://doi.org/10.1182/blood-2015-12-687749.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Feng X, Zhang L, Acharya C, An G, Wen K, Qiu L, et al. Targeting CD38 suppresses induction and function of T regulatory cells to mitigate immunosuppression in multiple myeloma. Clin Cancer Res. 2017;23:4290–300. https://doi.org/10.1158/1078-0432.CCR-16-3192.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. We declare no conflicts of interest.

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Authors and Affiliations

  1. Division of Hematology, Department of Medicine, Jichi Medical University, Tochigi, Japan

    Daisuke Minakata, Seina Honda, Ryutaro Tominaga, Daizo Yokoyama, Atsuto Noguchi, Shuka Furuki, Shunsuke Koyama, Rui Murahashi, Hirotomo Nakashima, Kazuki Hyodo, Shin-ichiro Kawaguchi, Takashi Ikeda, Yumiko Toda, Kiyomi Mashima, Kento Umino, Masuzu Ueda, Masahiro Ashizawa, Chihiro Yamamoto, Kaoru Hatano, Kazuya Sato, Ken Ohmine & Yoshinobu Kanda

  2. Division of Cell Transplantation and Transfusion, Jichi Medical University, Tochigi, Japan

    Shin-ichiro Fujiwara

  3. Department of Diagnostic Pathology, Jichi Medical University Hospital, Shimotsuke, Japan

    Noriyoshi Fukushima

  4. Division of Hematology, Jichi Medical University Saitama Medical Center, Saitama, Japan

    Yoshinobu Kanda

Authors
  1. Daisuke Minakata
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Contributions

DM collected data and wrote the manuscript; S.-i. Fujiwara designed this report, and interpreted the results; YK designed this report, interpreted the results, and wrote the manuscript; SH, RT, DY, AN, S.Furuki, S.Koyama, RM, HN, K.Hyodo, TI, S.-i. Kawaguchi, YT, KM, KU, MU, MA, CY, K.Hatano, KS, KO, and NF reviewed the manuscript, contributed to the interpretation of the data, and approved the final version.

Corresponding author

Correspondence to Yoshinobu Kanda.

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Competing interests

D.M. has received speaking fees from Janssen. M.A. has received speaking fees from Novartis. M.U. has received speaking fees from Janssen, Ono Pharma, Sanofi, Takeda, and BMS. S.-i.F. has received a scholarship from Daiichi Sankyo and honoraria from BMS, CSL Behring, Janssen, Nippon Kayaku, Novartis, Pfizer, Sanofi, and Takeda. K.O. serves as an advisor for Ono and has received speaking fees from Novartis, Takeda, and Ono. Y.K. has received research grants from Sanofi, Ono, Takeda, and Daiichi Sankyo, and payment or honoraria for lectures from BMS, Janssen, Sanofi, Novartis, Pfizer, Ono, Takeda, and Daiichi Sankyo. The other authors have no conflicts of interest to report.

Ethics approval and consent to participate

We confirm that all methods were performed in accordance with the relevant guidelines and regulations. This retrospective analysis was approved by the institutional review boards Jichi Medical University Hospital Bioethics Committee for Clinical Research [23-125, 31/Jan/2024]. Regarding the patient consent statement, this study was a retrospective analysis and did not require patient consent. An opt-out procedure was used, and participants were not included in the study if they explicitly decided to exclude. We have not released any personally identifiable images from human research participants in this study.

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Minakata, D., Fujiwara, Si., Honda, S. et al. Impact of daratumumab on the development of engraftment syndrome after autologous peripheral blood stem cell transplantation for multiple myeloma. Bone Marrow Transplant 60, 743–745 (2025). https://doi.org/10.1038/s41409-025-02558-6

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