Early data support panobinostat benefit in high-risk AML

  • DeAngelo DJ & al.
  • Leuk Res
  • 1 Aug 2019

  • curated by David Reilly
  • Univadis Clinical Summaries
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Takeaway

  • When combined with idarubicin+cytarabine, panobinostat demonstrated efficacy with a tolerable safety profile in patients aged ≤65 years with high-risk acute myeloid leukemia (AML).

Why this matters

  • In preclinical studies, decreasing the activity of histone deacetylases (HDAC) resulted in potentiation of standard chemotherapy against AML.

Study design

  • Phase 1b study to investigate idarubicin+cytarabine with escalating doses of oral panobinostat (15, 20, 25 mg) in 46 patients aged ≤65 years with high-risk AML.
  • 36 patients had primary AML; 10 had secondary AML.
  • Median patient age, 55.5 (range, 19-65) years.
  • Funding: Novartis Pharmaceuticals Corporation.

Key results

  • Overall response rate, 60.9% (95% CI, 45.4%-74.9%).
  • 43.5% achieved complete remission (CR).
  • 17.4% achieved CR with incomplete count recovery.
  • 1-year event-free survival, 78.3%.
  • 23.9% of patients discontinued treatment because of disease progression; 17.4% discontinued because of adverse events (AEs).
  • 41.3% experienced ≥1 serious AE (SAE) suspected as being treatment-related.
  • Grade ≥3 febrile neutropenia was the most common SAE.
  • Recommended phase 2 dose (RP2D) of panobinostat when combined with idarubicin+cytarabine: 20 mg.

Limitations

  • Limited sample size.