Phase I trial of histone deacetylase inhibitor panobinostat in addition to glucocorticoids for primary therapy of acute graft-versus-host disease

Lia Perez, Hugo Fernandez, Pedro Horna, Marcie Riches, Frederick Locke, Teresa Field, John Powers, Eva Sahakian, Alejandro Villagra, Asmita Mishra, Brian Betts, Mohamed Kharfan-Dabaja, Francisca Beato, Leonel Ochoa-Bayona, Joseph Pidala, Claudio Anasetti

Research output: Contribution to journalArticlepeer-review

3 Scopus citations

Abstract

Glucocorticoids for primary therapy of acute GVHD have limited responses. A phase I/II trial tested 4 weeks of deacetylase inhibitor panobinostat started within 48 h of glucocorticoids (1 mg/kg/day prednisone or equivalent) as primary treatment for patients with either classic acute GVHD (n = 16) or acute GVHD overlapping with chronic (n = 6). Four patients received 2.5 mg/m2 IV three times a week (TIW). Subsequent to discontinuation of IV panobinostat, patients received oral doses (PO). Two patients treated with 10 mg TIW (PO level 1) had progressive GVHD, after which patients were treated with 5 mg TIW (PO level −1; n = 16); 31/41 adverse events were possibly related, including thrombocytopenia (n = 13), leukopenia (n = 7), hypercholesterolemia (n = 3), hypertriglyceridemia (n = 5), anemia (n = 1), fatigue (n = 1), and hepatobiliary disorder (n = 1). GVHD responses were complete (n = 12) or partial (n = 3), with 1 progression at PO level −1. T-regulatory cells increased at day 8, CD4/CD8 and monocytes exhibited enhanced H3 acetylation, and CD4 or CD8 numbers remained unchanged with a decreased interleukin 12p40 plasma level. Panobinostat in combination with prednisone is safe and warrants further testing in GVHD.

Original languageEnglish (US)
Pages (from-to)1434-1444
Number of pages11
JournalBone marrow transplantation
Volume53
Issue number11
DOIs
StatePublished - Nov 1 2018
Externally publishedYes

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© 2018, Macmillan Publishers Limited, part of Springer Nature.

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