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Treatment of steroid resistant acute graft versus host disease with an anti-CD26 monoclonal antibody—Begelomab

Bone Marrow Transplantation volume 55, pages 1580–1587 (2020)Cite this article

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Abstract

We have treated 69 patients with steroid refractory acute graft versus host disease (SR-aGvHD), with an anti-CD26 monoclonal antibody (Begelomab): 28 patients in two prospective studies (EudraCT No. 2007-005809-21; EudraCT No. 2012-001353-19), and 41 patients on a compassionate use study. The median age of patients was 42 and 44 years; the severity of GvHD was as follows: grade II in 8 patients, grade III in 33, and grade IV in 28 patients. There were no adverse events directly attributable to the antibody. Day 28 response was 75% in the prospective studies and 61% in the compassionate use patients, with complete response rates of 11 and 12%. Response for grade III GvHD was 83 and 73% in the two groups; response in grade IV GvHD was 66 and 56% in the two groups. Non relapse mortality (NRM) at 6 months was 28 and 38%. Overall there were 64, 56, 68% responses for skin, liver, and gut stage 3–4 GvHD. The overall survival at 1 year was 50% for the prospective studies and 33% for the compassionate use patients. In conclusion, Begelomab induces over 60% responses in SR-aGvHD, including patients with severe gut and liver GvHD, having failed one or more lines of treatment.

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Fig. 1: Design of the study.
Fig. 2: Schedule of administration of the anti-CD26 antibody (Begelomab).
Fig. 3: GvHD grading on days 0, +5, +10, +28, +60, +90, in 28 patients treated on the prospective studies.
Fig. 4: Cumulative incidence of Non relapse mortality.
Fig. 5: Overal Kaplan Meier survival curves.

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References

  1. Flowers ME, Inamoto Y, Carpenter PA, Lee SJ, Kiem HP, Petersdorf EW, et al. Comparative analysis of risk factors for acute graft-versus-host disease and for chronic graft-versus-host disease according to National Institutes of Health consensus criteria. Blood. 2011;117:3214–9.

    Article  CAS  Google Scholar 

  2. Martin PJ, Rizzo JD, Wingard JR, Ballen K, Curtin PT, Cutler C, et al. First- and second-line systemic treatment of acute graft-versus-host disease: recommendations of the American Society of Blood and Marrow Transplantation. Biol Blood Marrow Transpl. 2012;18:1150–63.

    Article  Google Scholar 

  3. Ruutu T, Gratwohl A, de Witte T, Afanasyev B, Apperley J, Bacigalupo A, et al. Prophylaxis and treatment of GVHD: EBMT-ELN working group recommendations for a standardized practice. Bone Marrow Transpl. 2014;49:168–73.

    Article  CAS  Google Scholar 

  4. Mielcarek M, Storer BE, Boeckh M, Green ML, McDonald GB, Carpenter PA, et al. Initial therapy of acute graft-versus-host disease with low-dose prednisone does not compromise patient outcomes. Blood. 2009;113:2888–94.

    Article  CAS  Google Scholar 

  5. Van Lint MT, Milone G, Leotta S, Uderzo C, Scimè R, Dallorso S, et al. Treatment of acute graft-versus-host disease with prednisolone: significant survival advantage for day +5 responders and no advantage for nonresponders receiving anti-thymocyte globulin. Blood. 2006;107:4177–81.

    Article  Google Scholar 

  6. Lee SJ, Zahrieh D, Agura E, MacMillan M, Maziarz RT, McCarthy PL, et al. Effect of up-front daclizumab when combined with steroids for the treatment of acute graft-versus-host disease:results of a randomized trial. Blood. 2004;104:1559–64.

    Article  CAS  Google Scholar 

  7. Macmillan ML, Couriel D, Weisdorf DJ, Schwab G, Havrilla G, Fleming N, et al. A phase 2/3 multicenter randomized clinical trial of ABX-CBL versus ATG as secondary therapy for steroid-resistant acute graft-versus-host disease. Blood. 2007;109:2657–62.

    Article  CAS  Google Scholar 

  8. Nature News. Stem-cell drug fails crucial trials. Nature. 2009. https://doi.org/10.1038/news.2009.894.

  9. Bolaños-Meade J, Logan BR, Alousi AM, Antin JH, Barowski K, Carter SL, et al. Phase 3 clinical trial of steroids/mycophenolate mofetil vs steroids/placebo as therapy for acute GVHD: BMT CTN 0802. Blood. 2014;124:3221–7.

    Article  Google Scholar 

  10. Xhaard A, Rocha V, Bueno B, Peffault de Latour R, Lenglet J, Petropoulou A, et al. SR acute GvHD: lack of improved long term survival usng new generation anticytokine therapy. Biol Blood Marrow Transpl. 2012;18:406–13.

    Article  CAS  Google Scholar 

  11. Ohnuma K, Dang NH, Morimoto C. Revisiting an old acquaintance: CD26 and its molecular mechanisms in T cell function. Trends Immunol. 2008;29:295–300.

    Article  CAS  Google Scholar 

  12. Hatano R, Ohnuma K, Yamamoto J, Dang NH, Yamada T, Morimoto C. Humanized monoclonal antibody specific for CD26 ameliorates xenogeneic GVHD by human lymphocytes. Br J Haematol. 2013;162:263.

    Article  CAS  Google Scholar 

  13. Glucksberg H, Storb R, Fefer A, Buckner CD, Neiman PE, Clift R, et al. Clinical manifestations of graft-versus-host disease in human recipients of marrow from HL-A-matched sibling donors. Transplantation. 1974;18:295–304.

    Article  CAS  Google Scholar 

  14. Axt L, Naumann A, Toennies JH, Haen SP, Vogel W, Schneidawind D, et al. Retrospective single center analysis of outcome, risk factors and therapy in SR graft-versus-host disease after allogeneic hematopoietic cell transplantation. Bone Marrow Transplant. 2019. https://doi.org/10.1038/s41409-019-0544-y.

  15. Jagasia M, Greinix H, Robin M, Das Gupta E, Jacobs R, Savani BP, et al. Extracorporeal photopheresis versus anticytokine therapy as a second-line treatment for steroid-refractory acute GVHD: a multicenter comparative analysis. Biol Blood Marrow Transplant. 2013;19:1129–33.

    Article  CAS  Google Scholar 

  16. Ringden O, Arjang Baygan A, Remberger M, Gustafsson B, Winiarski CJ, Khoein B, et al. Placenta-derived decidua stromal cells for treatment of severe acute graft-versus-host disease. Stem Cells Transl Med. 2018;7:325–32.

    Article  CAS  Google Scholar 

  17. Groth C, Lenneke G, van Groningen FJ, Matos TR, Bremmers ME, Preijers FWMB, et al. Phase I/II trial of a combination of anti-CD3/CD7 immunotoxins for steroid-refractory acute graft-versus-host disease. Biol Blood Marrow Transpl. 2019;25:712719.

    Article  Google Scholar 

  18. Fløisand Y, Lazarevic VLJ, Maertens J, Mattsson J, Shah VN, Zachee P, et al. Safety and effectiveness of vedolizumab in patients with steroid- refractory gastrointestinal acute graft-versus-host disease: a retrospective record review. Biol Blood Marrow Transpl. 2019;25:720–7.

    Article  Google Scholar 

  19. Marcondes AM, Hockenbery D, Lesnikova M, Dinarello CA, Woolfrey A, Gernsheimer T, et al. Response of steroid-refractory acute GVHD to a1-antitrypsin. Biol Blood Marrow Transpl. 2016;22:1596–601.

    Article  CAS  Google Scholar 

  20. Bader P, Kuçi Z, Bakhtiar S, Basu O, Bug G, Dennis M, et al. Effective treatment of steroid and therapy-refractory acute graft-versus-host disease with a novel mesenchymal stromal cell product (MSC-FFM). Bone Marrow Transplant. 2018;53:852–62.

    Article  CAS  Google Scholar 

  21. Zeiser R, Burchert A, Lengerke C, Verbeek M, Maas-Bauer K, Metzelder SK, et al. Ruxolitinib in corticosteroid-refractory graft-versus-host disease after allogeneic stem cell transplantation: a multicenter survey. Leukemia. 2015;29:2062–8.

    Article  CAS  Google Scholar 

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Acknowledgements

This study was supported by FARITMO, Genova Italy and Associazione Italian Ricerca contro il Cancro (AIRC), Milano, Italy. We thank ADIENNE SA Lugano Switzerland, for the generous supply of Begelomab in the compassionate use study. We thank the nurses of our transplant centers for excellent care of these difficult patients.

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Authors and Affiliations

  1. Universita’ Cattolica del Sacro Cuore, Roma, Italy

    Andrea Bacigalupo, Patrizia Chiusolo & Simona Sica

  2. Istituto di Ematologia, Fondazione Policlinico Universitario Gemelli, IRCCS, Roma, Italy

    Andrea Bacigalupo

  3. UOC Ematologia e Trapianto di Midollo Osseo, IRCCS Ospedale Policlinico San Martino Genova, Genova, Italy

    Emanuele Angelucci, Anna Maria Raiola, Riccardo Varaldo, Carmen Di Grazia & Francesca Gualandi

  4. Department of Translational Research on New Technology in Medicine and Surgery; Universita’ di Pisa, Pisa, Italy

    Edoardo Benedetti

  5. Dipartimento di Medicina Clinica e Chirurgica, Universita’ Federico II, Napoli, Italy

    Antonio Risitano

  6. UOC di oncoematologia e TMO, Dipartimento Oncologico “la Maddalena”, Palermo, Italy

    Maurizio Musso

  7. Divisione di Ematologia, Azienda Ospedaliera SS. Antonio e Biagio e Cesare Arrigo, Alessandria, Italy

    Francesco Zallio

  8. IRCCS Ospedale San Raffaele; University Vita-Salute San Raffaele, Milano, Italy

    Fabio Ciceri

  9. Universita’ Cattolica del Sacro Cuore, Roma, Italy

    Patrizia Chiusolo & Simona Sica

  10. Dipartimento di Oncologia ed Ematologia Università di Milano e Azienda Socio-Sanitaria Territoriale Papa Giovanni XXIII, Bergamo, Bergamo, Italy

    Alessandro Rambaldi

  11. Department of Hematology “L. & A. Seràgnoli” University Hospital S. Orsola-Malpighi, Bologna, Italy

    Francesca Bonifazi

  12. Istituto di Ematologia, Ospedale S Gerardo, Monza, Italy

    Matteo Parma

  13. Centro Trapianti Midollo Osseo, Grande Ospedale Metropolitano “BMM”, Reggio Calabria, Calabria, Italy

    Massimo Martino

  14. Hematology-BMT Center, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico – University of Milan, Milano, Italy

    Francesco Onida

  15. UOC Ematologia, Policlinico Umberto 1, Roma, Italy

    Anna Paola Iori

  16. Divisione di Ematologia, Ospedale S Giovanni di Dio, Salerno, Italy

    Carmine Selleri

  17. Divisione di Ematologia, Ospedale San Bortolo, Vicenza, Italy

    Carlo Borghero

  18. Division of Stem Cell Transplantation and Regenerative Medicine, Department of Pediatrics, Stanford School of Medicine, Stanford, CA, USA

    Alice Bertaina

  19. UO Ematologia e CTMO, Universita’ di Parma, Parma, Italy

    Lucia Prezioso

  20. Dipartimento di Oncoematologia Pediatrica, IRCCS, Ospedale Pediatrico Bambino Gesu’, Sapienza, Università di Roma, Roma, Italy

    Mattia Algeri & Franco Locatelli

Authors
  1. Andrea Bacigalupo
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  2. Emanuele Angelucci
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  3. Anna Maria Raiola
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  5. Carmen Di Grazia
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  6. Francesca Gualandi
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  7. Edoardo Benedetti
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  8. Antonio Risitano
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  9. Maurizio Musso
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  11. Fabio Ciceri
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  14. Alessandro Rambaldi
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  15. Francesca Bonifazi
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  16. Matteo Parma
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  17. Massimo Martino
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  18. Francesco Onida
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  19. Anna Paola Iori
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  20. Carmine Selleri
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  21. Carlo Borghero
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  22. Alice Bertaina
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  23. Lucia Prezioso
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  24. Mattia Algeri
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  25. Franco Locatelli
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Contributions

AB, FL, and FC designed the studies, contributed patients, analyzed the data and wrote the manuscript; FG, AMR, RV, CDG, EA, ARi, ARa, MM, FZ, PC, SS, AR, FB, MP, FO, API, CS, CB, AB, MA contributed patients and revised the paper.

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Correspondence to Andrea Bacigalupo.

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The authors declare that they have no conflict of interest.

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Bacigalupo, A., Angelucci, E., Raiola, A.M. et al. Treatment of steroid resistant acute graft versus host disease with an anti-CD26 monoclonal antibody—Begelomab. Bone Marrow Transplant 55, 1580–1587 (2020). https://doi.org/10.1038/s41409-020-0855-z

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