A phase 2 trial of the histone deacetylase inhibitor panobinostat for graft-versus-host disease prevention

Lia Perez, Hugo Fernandez, Mohamed Kharfan-Dabaja, Farhad Khimani, Brian Betts, Asmita Mishra, Ernesto Ayala, Frederick L. Locke, Leonel Ochoa-Bayona, Michael Nieder, Joseph Pidala, Alex Achille, John Powers, Eva Sahakian, Ram Thapa, Xuefeng Wang, Claudio Anasetti

Research output: Contribution to journalArticlepeer-review

6 Scopus citations


Immunomodulatory properties of histone deacetylase inhibitors represent a reasonable approach for acute graft-versus-host disease (aGVHD) prevention. We report a phase 2 trial evaluating panobinostat (PANO) administered over 26 weeks, starting on day -5 (5 mg orally 3 times a week) with tacrolimus initiated on day -3 plus sirolimus on day -1, with a median patient age of 58 years (range, 19-72 years) (n = 38). Donor source consisted of HLA 8/8-matched donors, related (n = 13) or unrelated (n = 25), using granulocyte colony-stimulating factor-stimulated peripheral blood stem cells. Myeloablative (n = 18) or reduced-intensity (n = 20) conditioning regimens were used for patients with acute myeloid leukemia (n = 17), myelodysplastic syndrome (n = 13), or other malignancies (n = 8). The cumulative incidence of aGVHD II-IV by day 100 was 18.4% (90% confidence interval [CI], 9.4% to 29.9%). Cumulative incidence of chronic GVHD at 1 year was 31.6% (90% CI, 19.5% to 44.3%). Adverse events related to PANO were thrombocytopenia (n = 5), leukopenia (n = 6), gastrointestinal toxicity (n = 3), rash (n = 4), renal failure/peripheral edema (n = 1), and periorbital edema (n = 1). At 1 year, overall survival was 89.5% (90% CI, 81.6% to 98.0%), relapse-free survival was 78.9% (90% CI, 68.8% to 90.6%), nonrelapse mortality was 2.6% (90% CI, 0.3% to 9.9%), and GVHD relapse-free survival was 60.5% (90% CI, 48.8% to 75.1%). PANO hits histone 3 as early as day 15 in CD8, CD4 and T regs. In conclusion, PANO combination met the primary study end point for aGVHD prevention and warrants further testing. This trial was registered at www.clinicaltrials.gov as #NCT02588339.

Original languageEnglish (US)
Pages (from-to)2740-2750
Number of pages11
JournalBlood Advances
Issue number13
StatePublished - Jul 13 2021
Externally publishedYes

Bibliographical note

Publisher Copyright:
© 2021 by The American Society of Hematology.


  • Adult
  • Aged
  • Graft vs Host Disease/prevention & control
  • Hematopoietic Stem Cell Transplantation
  • Histone Deacetylase Inhibitors/therapeutic use
  • Humans
  • Middle Aged
  • Panobinostat
  • Transplantation Conditioning
  • Young Adult

PubMed: MeSH publication types

  • Clinical Trial, Phase II
  • Journal Article


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