ruxolitinib + enasidenib

**Ruxolitinib + enasidenib** is an investigational combination therapy consisting of ruxolitinib, a selective Janus kinase (JAK) 1/2 inhibitor, and enasidenib, an inhibitor of isocitrate dehydrogenase 2 (IDH2). This combination is being evaluated for patients with advanced myeloproliferative neoplasms (MPN) in accelerated or blast phase, as well as for chronic-phase myelofibrosis (MF) with 4–9% circulating blasts. The rationale for combination therapy is based on the complementary mechanisms: ruxolitinib targets the aberrant JAK-STAT signaling pathway common in MPN, while enasidenib inhibits mutant IDH2-driven oncogenic metabolism, which can be present in MPN progression or transformation to acute myeloid leukemia. Preclinical studies demonstrated synergistic inhibition of disease progression in mutant JAK2/IDH2 models, and early-phase clinical trials suggest clinical activity and manageable safety.