- 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.
- 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.
- 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.
- Limited sample size.