Azacitidine for the treatment of steroid-refractory chronic graft-versus-host disease: the results of the phase II AZTEC clinical trial

Ram Malladi; Ikhlaaq Ahmed; Graham McIlroy; Fiona L. Dignan; Rachel Protheroe; Aimee Jackson; Paul Moss; Jane Nunnick; Shamyla Siddique; Rebecca Bishop; Mohamed Elhaneid; Andrea Hodgkinson; Charles Craddock

doi:10.1038/s41409-021-01439-y

Azacitidine for the treatment of steroid-refractory chronic graft-versus-host disease: the results of the phase II AZTEC clinical trial

Ram Malladi^*, Ikhlaaq Ahmed, Graham McIlroy, Fiona L. Dignan, Rachel Protheroe, Aimee Jackson, Paul Moss, Jane Nunnick, Shamyla Siddique, Rebecca Bishop, Mohamed Elhaneid, Andrea Hodgkinson, Charles Craddock

^*Corresponding author for this work

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Abstract

Chronic graft-versus-host disease (cGvHD) is a major cause of non-relapse morbidity and mortality following allogeneic stem cell transplant. Over half of patients with moderate or severe cGvHD fail to respond adequately to first-line treatment with systemic steroids, and although a range of second-line options have been employed, a lack of prospective evidence means there is no standard of care. The AZTEC trial is a prospective, single-arm, phase II study investigating the safety and activity of azacitidine for the treatment of cGvHD in patients who are resistant to, or intolerant of, systemic steroid therapy. The co-primary outcomes were treatment tolerability, and activity measured as objective response according to modified National Institutes of Health criteria. Fourteen patients were recruited to the first stage of the trial, of whom seven completed the planned six cycles of azacitidine 36 mg/m² days 1–5 per 28-day cycle. Azacitidine was tolerated by 13/14 patients, and 7/14 showed an objective response. Clinical responses were mirrored by improvements in patient-reported cGvHD symptoms and quality of life. AZTEC demonstrates that azacitidine is a safe and promising option for the treatment of cGvHD, and continued evaluation in the second stage of this phase II efficacy study is supported.

Original language	English
Pages (from-to)	2948-2955
Number of pages	8
Journal	Bone Marrow Transplantation
Volume	56
Issue number	12
Early online date	26 Aug 2021
DOIs	https://doi.org/10.1038/s41409-021-01439-y
Publication status	Published - Dec 2021

Bibliographical note

Funding Information:
RM has received travel assistance from Celgene. FLD has received travel assistance from Gilead and Jazz; speaker’s fees from Mallinckrodt, Jazz, Pfizer and Janssen; advisory board for Kiadis, Jazz. CC has received research funding from Celgene. All other authors report no competing interests.

The AZTEC trial was funded by Bloodwise (now Blood Cancer UK). Azacitidine was provided free of charge by Celgene. The trial was supported by the facilities funded through Birmingham Science City Translational Medicine Clinical Research Infrastructure and Trials Platform, an Advantage West Midlands (AWM) funded project that forms part of the Science City University of Warwick and University of Birmingham Research Alliance.

Publisher Copyright:
© 2021, The Author(s), under exclusive licence to Springer Nature Limited.

ASJC Scopus subject areas

Hematology
Transplantation

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10.1038/s41409-021-01439-y

MalladiR2021Azacitidine
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Cite this

Malladi, R., Ahmed, I., McIlroy, G., Dignan, F. L., Protheroe, R., Jackson, A., Moss, P., Nunnick, J., Siddique, S., Bishop, R., Elhaneid, M., Hodgkinson, A., & Craddock, C. (2021). Azacitidine for the treatment of steroid-refractory chronic graft-versus-host disease: the results of the phase II AZTEC clinical trial. Bone Marrow Transplantation, 56(12), 2948-2955. Advance online publication. https://doi.org/10.1038/s41409-021-01439-y

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title = "Azacitidine for the treatment of steroid-refractory chronic graft-versus-host disease: the results of the phase II AZTEC clinical trial",

abstract = "Chronic graft-versus-host disease (cGvHD) is a major cause of non-relapse morbidity and mortality following allogeneic stem cell transplant. Over half of patients with moderate or severe cGvHD fail to respond adequately to first-line treatment with systemic steroids, and although a range of second-line options have been employed, a lack of prospective evidence means there is no standard of care. The AZTEC trial is a prospective, single-arm, phase II study investigating the safety and activity of azacitidine for the treatment of cGvHD in patients who are resistant to, or intolerant of, systemic steroid therapy. The co-primary outcomes were treatment tolerability, and activity measured as objective response according to modified National Institutes of Health criteria. Fourteen patients were recruited to the first stage of the trial, of whom seven completed the planned six cycles of azacitidine 36 mg/m2 days 1–5 per 28-day cycle. Azacitidine was tolerated by 13/14 patients, and 7/14 showed an objective response. Clinical responses were mirrored by improvements in patient-reported cGvHD symptoms and quality of life. AZTEC demonstrates that azacitidine is a safe and promising option for the treatment of cGvHD, and continued evaluation in the second stage of this phase II efficacy study is supported.",

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note = "Funding Information: RM has received travel assistance from Celgene. FLD has received travel assistance from Gilead and Jazz; speaker{\textquoteright}s fees from Mallinckrodt, Jazz, Pfizer and Janssen; advisory board for Kiadis, Jazz. CC has received research funding from Celgene. All other authors report no competing interests. The AZTEC trial was funded by Bloodwise (now Blood Cancer UK). Azacitidine was provided free of charge by Celgene. The trial was supported by the facilities funded through Birmingham Science City Translational Medicine Clinical Research Infrastructure and Trials Platform, an Advantage West Midlands (AWM) funded project that forms part of the Science City University of Warwick and University of Birmingham Research Alliance. Publisher Copyright: {\textcopyright} 2021, The Author(s), under exclusive licence to Springer Nature Limited.",

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Malladi, R, Ahmed, I, McIlroy, G, Dignan, FL, Protheroe, R, Jackson, A , Moss, P, Nunnick, J, Siddique, S, Bishop, R, Elhaneid, M, Hodgkinson, A & Craddock, C 2021, 'Azacitidine for the treatment of steroid-refractory chronic graft-versus-host disease: the results of the phase II AZTEC clinical trial', Bone Marrow Transplantation, vol. 56, no. 12, pp. 2948-2955. https://doi.org/10.1038/s41409-021-01439-y

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Azacitidine for the treatment of steroid-refractory chronic graft-versus-host disease: the results of the phase II AZTEC clinical trial

Abstract

Bibliographical note

ASJC Scopus subject areas

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