Oral histone deacetylase inhibitor tucidinostat (HBI-8000) in patients with relapsed or refractory adult T-cell leukemia/lymphoma: Phase IIb results

Cancer Sci. 2022 Aug;113(8):2778-2787. doi: 10.1111/cas.15431. Epub 2022 Jun 7.

Abstract

This multicenter, prospective phase IIb trial evaluating the efficacy and safety of tucidinostat (HBI-8000) in patients with relapsed or refractory (R/R) adult T-cell leukemia/lymphoma (ATLL) was undertaken in Japan. Eligible patients had R/R ATLL and had failed standard of care treatment with chemotherapy and with mogamulizumab. Twenty-three patients received tucidinostat 40 mg orally twice per week and were included in efficacy and safety analyses. The primary end-point was objective response rate (ORR) assessed by an independent committee. The ORR was 30.4% (95% confidence interval [CI], 13.2, 52.9]. Median progression-free survival was 1.7 months (95% CI, 0.8, 7.4), median duration of response was 9.2 months (95% CI, 2.6, not reached), and median overall survival was 7.9 months (95% CI, 2.3, 18.0). All patients experienced adverse events (AEs), which were predominantly hematologic and gastrointestinal. Incidence of grade 3 or higher AEs was 78.3%; most were laboratory abnormalities (decreases in platelets, neutrophils, white blood cells, and hemoglobin). Tucidinostat was well tolerated with AEs that could be mostly managed with supportive care and dose modifications. Tucidinostat is a meaningful treatment option for R/R ATLL patients; further investigation is warranted.

Keywords: ATLL; HBI-8000; HDAC inhibitor; ORR; tucidinostat.

Publication types

  • Multicenter Study

MeSH terms

  • Adult
  • Benzamides
  • Histone Deacetylase Inhibitors / adverse effects
  • Humans
  • Leukemia-Lymphoma, Adult T-Cell* / drug therapy
  • Lymphoma, Follicular* / drug therapy
  • Prospective Studies
  • Pyridines
  • Recurrence
  • Treatment Outcome

Substances

  • Benzamides
  • HBI-8000
  • Histone Deacetylase Inhibitors
  • Pyridines