0000000000993883
AUTHOR
Amjad Hayat
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 debilitat...
Efficacy, Safety, and Confirmation of the Recommended Phase 2 Starting Dose of the Combination of Ruxolitinib (RUX) and Panobinostat (PAN) in Patients (Pts) with Myelofibrosis (MF)
Abstract BACKGROUND: MF is a myeloproliferative neoplasm characterized by bone marrow (BM) fibrosis, splenomegaly, and debilitating constitutional symptoms. RUX is a potent JAK1/JAK2 inhibitor that has demonstrated superiority in spleen volume reduction, symptom improvement, and survival in the phase 3 COMFORT studies compared with placebo and best available therapy. PAN, a potent pan-deacetylase inhibitor, inhibits JAK signaling by disrupting the interaction between JAK2 and heat shock protein 90, a protein chaperone. PAN has demonstrated reductions in splenomegaly and improvement of BM fibrosis in phase 1/2 studies. The combination of RUX and PAN demonstrated synergistic activity in precl…
Efficacy, Safety, and Confirmation of the Recommended Phase 2 Dose of Ruxolitinib Plus Panobinostat in Patients with Intermediate or High-Risk Myelofibrosis
Abstract Background: Myelofibrosis (MF) is a clonal neoplastic disease resulting in bone marrow fibrosis, splenomegaly, and debilitating constitutional symptoms. The Janus kinase (JAK) pathway is often dysregulated in MF, and agents targeting this pathway have demonstrated efficacy in this disease. Ruxolitinib (RUX), a potent JAK1/JAK2 inhibitor, demonstrated superiority in spleen volume reduction, symptom improvement, and survival compared with the control arm in the phase III COMFORT-I and COMFORT-II studies. Panobinostat (PAN), a potent pan-deacetylase inhibitor (pan-DACi), inhibits JAK signaling through disruption of the interaction of JAK2 with the protein chaperone heat shock protein …