Clinical Evidence and Impact of Newer JAK Inhibitors in Myelofibrosis

The approvals of fedratinib and pacritinib were supported by pivotal clinical trials demonstrating significant reductions in splenomegaly and symptom burden, particularly in patients with thrombocytopenia or those intolerant to prior JAK inhibitor therapy. Their introduction expanded treatment options beyond ruxolitinib, enabling more personalized therapy based on patient-specific cytopenias and risk profiles. Momelotinib’s approval was informed by two key trials. The MOMENTUM study evaluated symptomatic, anemic patients previously treated with JAK inhibitors, showing improvements in transfusion independence, spleen volume, and symptom scores. SIMPLIFY-1 assessed momelotinib versus ruxolitinib in JAK inhibitor–naïve patients, confirming non-inferiority for spleen volume reduction and demonstrating added benefits for anemia management. Collectively, these studies not only established the efficacy and safety of next-generation JAK inhibitors but also reshaped treatment sequencing, highlighting the importance of addressing both splenomegaly and anemia in comprehensive myelofibrosis care.