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Phase II trial of natalizumab with corticosteroids as initial treatment of gastrointestinal acute graft-versus-host disease

Bone Marrow Transplantation volume 56, pages 1006–1012 (2021)Cite this article

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A Correction to this article was published on 12 October 2020

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Abstract

The α4ß7 integrin is upregulated on naive and memory T cell subsets in patients who subsequently develop gastrointestinal (GI) acute GVHD. Natalizumab (Tysabri®, Biogen Inc.) acts against the α4 subunit that mediates homing of lymphocytes to the GI tract. We initiated a phase II study of natalizumab with corticosteroids for initial treatment of acute GI GVHD. In total, 300 mg IV of natalizumab was given, with steroids initiated up to 3 days prior. Twenty-one subjects were treated, median age was 63 years (range 38–74), and 15 (71%) were male. Eighteen (86%) underwent RIC, 15 (71%) received MUD, and all received PBSCs. Overall GVHD at enrollment was grade II in 4 and grade III in 17. The primary endpoint, day 56 GVHD-free survival rate, was attained in 33.3%. The overall response rate at day 28 and 56 was 57% and 52%, respectively. Six of eight CRs were durable for 1 year. Five experienced toxicity possibly related to natalizumab and ten had infections before day 100. 2-year OS was 43% (95% CI 22–62%) and 2-year NRM was 52% (95% CI 29–71%). Natalizumab with corticosteroids as initial treatment of acute GI GVHD is safe, effective, and durable.

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Fig. 1: Acute GVHD Staging at Enrollment and Response Rates.
Fig. 2

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Change history

  • 05 October 2020

    The original version of the Article stated in the Methods section that Natalizumab was provided by Genentech. In fact, it was provided by Biogen. This has now been corrected in both the PDF and HTML versions of the Article.

  • 12 October 2020

    A Correction to this paper has been published: https://doi.org/10.1038/s41409-020-01083-y

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Authors and Affiliations

  1. Division of Hematology, The Ottawa Hospital, Ottawa, ON, Canada

    Natasha Kekre

  2. Department of Data Sciences, Dana-Farber Cancer Institute, Harvard School of Public Health, Boston, MA, USA

    Haesook T. Kim

  3. Division of Hematologic Malignancies, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA

    Julia Hofer, Vincent T. Ho, John Koreth, Philippe Armand, Sarah Nikiforow, Mahasweta Gooptu, Rizwan Romee, Edwin P. Alyea, Prashant Nageshwar, Brett Glotzbecker, Robert J. Soiffer, Joseph H. Antin & Corey Cutler

  4. Blood and Marrow Transplant Program, Massachusetts General Hospital, Boston, MA, USA

    Areej El-Jawahri, Zachariah DeFilipp & Yi-Bin Chen

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Correspondence to Corey Cutler.

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Kekre, N., Kim, H.T., Hofer, J. et al. Phase II trial of natalizumab with corticosteroids as initial treatment of gastrointestinal acute graft-versus-host disease. Bone Marrow Transplant 56, 1006–1012 (2021). https://doi.org/10.1038/s41409-020-01049-0

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