In one study, A. Surrreda presented results from an ongoing large Phase II study of the oral pan histone deacetylase inhibitor (HDACi) in patients with relapsed HL. Remarkably, despite the relative rarity of the patient population, this international trial has completed enrollment with 129 patients at 45 sites in 13 countries.
Oral panobinostat was administered at a dose of 40 mg three times per week, every week, in 21-day cycles. Dose delays and reductions were allowed for management of toxicity. Patients had a median age of 32 years, with a median prior treatment regimens of four. Importantly, 37% had no response on last therapy and 80% had a prior autologous stem cell transplant.
Based on objective response assessment, 17 patients achieved major responses and 71% of the patients had tumor reductions. Common grade 1 and 2 toxicity included nausea, vomiting, and diarrhea. The most common grade 3 and 4 toxicity were thrombocytopenia and anemia. Thus, this study confirms the clinical activity of HDACi in HL.
However, this study is the largest single agent Phase II study to be conducted in patients with relapsed HL, after receiving ASCT, which represents a population of unmet medical need. The final analysis of this study is expected to be available by the end of this year.
While the single agent activity looks very promising, panobinostat-based combination clinical trials are currently enrolling patients with relapsed HL. One interesting study is a combination of everolimus plus panobinostat, which is currently enrolling patients at MD Anderson.In a second study, N. Fowler presented very exciting data from an ongoing Phase I study using the oral Bruton's tyrosine Kinase (Btk) inhibitor PCI32765 in patients with relapsed B cell lymphoma. Btk is an important component of B-cell receptor signaling pathway, downstream of Syk.