A phase 1b/2b multicenter study of oral panobinostat plus azacitidine in adults with MDS, CMML or AML with ≤30% blasts

G. Garcia-Manero, M. A. Sekeres, M. Egyed, M. Breccia, C. Graux, J. D. Cavenagh, H. Salman, A. Illes, P. Fenaux, D. J. Deangelo, R. Stauder, K. Yee, N. Zhu, J. H. Lee, D. Valcarcel, A. Macwhannell, Z. Borbenyi, L. Gazi, S. Acharyya, S. IdeM. Marker, O. G. Ottmann

Research output: Contribution to journalArticle

23 Scopus citations

Abstract

Treatment with azacitidine (AZA), a demethylating agent, prolonged overall survival (OS) vs conventional care in patients with higher-risk myelodysplastic syndromes (MDS). As median survival with monotherapy is o2 years, novel agents are needed to improve outcomes. This phase 1b/2b trial (n = 113) was designed to determine the maximum tolerated dose (MTD) or recommended phase 2 dose (RP2D) of panobinostat (PAN)+AZA (phase 1b) and evaluate the early efficacy and safety of PAN+AZA vs AZA monotherapy (phase 2b) in patients with higher-risk MDS, chronic myelomonocytic leukemia or oligoblastic acute myeloid leukemia with o30% blasts. The MTD was not reached; the RP2D was PAN 30 mg plus AZA 75 mg/m2. More patients receiving PAN +AZA achieved a composite complete response ([CR)+morphologic CR with incomplete blood count+bone marrow CR (27.5% (95% CI, 14.6-43.9%)) vs AZA (14.3% (5.4-28.5%)). However, no significant difference was observed in the 1-year OS rate (PAN+AZA, 60% (50-80%); AZA, 70% (50-80%)) or time to progression (PAN+AZA, 70% (40-90%); AZA, 70% (40-80%)). More grade 3/4 adverse events (97.4 vs 81.0%) and on-Treatment deaths (13.2 vs 4.8%) occurred with PAN+AZA. Further dose or schedule optimization may improve the risk/benefit profile of this regimen.

Original languageEnglish (US)
Pages (from-to)2799-2806
Number of pages8
JournalLeukemia
Volume31
Issue number12
DOIs
StatePublished - Jan 1 2017

ASJC Scopus subject areas

  • Hematology
  • Oncology
  • Cancer Research

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    Garcia-Manero, G., Sekeres, M. A., Egyed, M., Breccia, M., Graux, C., Cavenagh, J. D., Salman, H., Illes, A., Fenaux, P., Deangelo, D. J., Stauder, R., Yee, K., Zhu, N., Lee, J. H., Valcarcel, D., Macwhannell, A., Borbenyi, Z., Gazi, L., Acharyya, S., ... Ottmann, O. G. (2017). A phase 1b/2b multicenter study of oral panobinostat plus azacitidine in adults with MDS, CMML or AML with ≤30% blasts. Leukemia, 31(12), 2799-2806. https://doi.org/10.1038/leu.2017.159