A phase 1b, dose-finding study of ruxolitinib plus panobinostat in patients with myelofibrosis.

7022^ Background: Myelofibrosis (MF) is a myeloproliferative neoplasm characterized by dysregulation of the Janus kinase (JAK) pathway resulting in bone marrow fibrosis, splenomegaly, and debilitating symptoms. Ruxolitinib (RUX) is a potent JAK1/JAK2 inhibitor that decreased spleen volume, improved symptoms, and prolonged survival in phase 3 studies. Panobinostat (PAN) is a potent pan-deacetylase inhibitor (DACi) that has shown splenomegaly reduction and improvement of marrow fibrosis in phase 1/2 studies. RUX and PAN demonstrated synergistic anti-MF activity in preclinical studies. Here, we present the updated results of a phase 1b study of the combination of RUX and PAN in MF patients (pts). Methods: Eligible pts had intermediate-1, -2, or high-risk MF by International Prognostic Scoring System criteria with palpable splenomegaly. Pts received RUX (5-15 mg) twice daily, every day (BID) and PAN (10-25 mg) once daily, 3 times a week (TIW; days 2, 4, and 6), every other week (QOW) in a 28-day cycle. The pr...