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

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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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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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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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 (2020). https://doi.org/10.1038/s41409-020-0855-z

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