Perez L, Fernandez H, Kharfan-Dabaja M, et al. A Phase 2 Trial of the Histone Deacetylase Inhibitor Panobinostat for Graft-Versus-Host Disease Prevention. Blood Advances. 2021; 5 (13): 2740 (doi: 10.1182/bloodadvances.2021004225).
The histone deacetylase inhibitor panobinostat (PANO) effectively prevented acute graft-versus-host disease (aGVHD) when combined with tacrolimus and sirolimus in a phase 2 trial. PANO was administered over 26 weeks, starting on day -5, with 5 mg taken orally 3 times weekly. Tacrolimus was added to the regimen on day -3 and sirolimus on day -1. There were 38 participants, with a median age of 58 years. Donor sources were Human Leukocyte Antigen 8/8-matched donors (13 related and 25 unrelated) using granulocyte colony-stimulating factor-stimulated peripheral blood stem cells. Seventeen patients with acute myeloid leukemia, 13 with myelodysplastic syndrome, and 8 with other malignancies received myeloablative (18) or reduced-intensity (20) conditioning regimens. The cumulative incidence (CI) of aGVHD II-IV by day 100 was 18.4%, while the CI for chronic GVHD was 31.6% at 1 year. Adverse events included thrombocytopenia, leukopenia, gastrointestinal toxicity, rash, renal failure/peripheral edema, and periorbital edema. Overall survival was 89.5% at 1 year, while relapse-free survival was 78.9%, nonrelapse mortality was 2.6%, and GVHD relapse-free survival was 60.5%.