SOHO State of the Art Updates and Next Questions| Individualizing Treatment Selection in Myelofibrosis

Myelofibrosis is an advanced myeloproliferative neoplasm that is biologically driven by constitutively active JAK-STAT signaling. Resultant effects on hematopoiesis and inflammatory cytokine signaling give rise to an array of clinical manifestations that include proliferative features, splenomegaly, constitutional symptoms, cytopenias, propensity towards leukemic transformation, and risk of thrombosis, with patients exhibiting a high degree of variability in regard to clinical course. This necessitates an individualized treatment approach that accounts for a variety of clinical and therapy-specific factors. JAK inhibitors have emerged as the cornerstone of therapy. With 4 agents now approved in the class, selecting the appropriate agent is of critical importance. In this review we discuss key variables that should be considered in the creation of a therapeutic plan for patients with myelofibrosis. We will review pharmacologic differences between available JAK inhibitors, discuss the patient factors that drive therapy decisions in myelofibrosis, and highlight emerging therapies in the field.