Phase 1 study of belinostat (PXD-101) and bortezomib (Velcade, PS-341) in patients with relapsed or refractory acute leukemia and myelodysplastic syndrome.

Journal Article (Journal Article)

We report the results of a phase 1 dose-escalation study of belinostat and bortezomib in adult patients with acute leukemia or MDS or CML with blast crisis. Thirty-eight patients received IV belinostat days 1-5 and 8-12 with IV bortezomib days 1, 4, 8, and 11 every 21 days. QTc prolongation was the only identified DLT. The RP2Ds were 1.3 mg/m2 bortezomib and 1000 mg/m2 belinostat. One patient with highly refractory MLL-ENL rearranged biphenotypic AML with multiple karyotypic aberrations had a complete pathologic and karyotypic response. One patient with post-MPN AML remained on study with stable disease (SD) for 32 cycles. Whole-exome sequencing revealed no aberrations in the first patient and a hyper-mutator genotype in the second. Eighteen patients had a best response of SD. We conclude that this treatment strategy is feasible but has limited activity in this population. Nevertheless, the factors that predict exceptional responses to this strategy warrant further investigation.

Full Text

Duke Authors

Cited Authors

  • Holkova, B; Shafer, D; Yazbeck, V; Dave, S; Bose, P; Tombes, MB; Shrader, E; Wan, W; Bandyopadhyay, D; Weir, C; Collins, EB; Garnett, A; Kmieciak, M; Roberts, JD; Garcia-Manero, G; Grant, S

Published Date

  • May 1, 2021

Published In

Volume / Issue

  • 62 / 5

Start / End Page

  • 1187 - 1194

PubMed ID

  • 33356689

Pubmed Central ID

  • PMC8106643

Electronic International Standard Serial Number (EISSN)

  • 1029-2403

Digital Object Identifier (DOI)

  • 10.1080/10428194.2020.1861270


  • eng

Conference Location

  • United States