Pacritinib in Myelofibrosis: Evidence on Spleen Volume Reduction and Symptom Control

　　Myelofibrosis is a myeloproliferative neoplasm characterized by splenomegaly,anemia,thrombocytopenia,and constitutional symptoms such as fatigue,night sweats,weight loss,and bone pain.Pacritinib inhibits JAK2 and IRAK1-mediated signaling,dampening aberrant cytokine activity and the inflammatory drive of the disease.This dual mechanism translates into both spleen volume reduction and symptom relief,and is of particular interest for patients with significantly reduced platelet counts.

　　In the phase III PERSIST-1 trial,327 patients with myelofibrosis were enrolled.At week 24,19%of patients receiving pacritinib achieved a spleen volume reduction of at least 35%(SVR35),compared with 5%in the best available therapy(BAT)arm.Sustained improvement in disease-related symptoms was also observed.

　　PERSIST-2 enrolled 311 patients with platelet counts of 100×10⁹/L or below.Among those with baseline platelets below 50×10⁹/L,29%of patients treated with pacritinib 200 mg twice daily achieved SVR35 at week 24,versus 3.1%with BAT—indicating that clinically meaningful spleen responses are attainable even in severe thrombocytopenia.

　　Symptom burden was assessed using the Total Symptom Score(TSS),covering fatigue,early satiety,abdominal discomfort,night sweats,pruritus,and bone pain.A 2025 exploratory analysis of PERSIST-2 reported that 32.4%of pacritinib-treated patients achieved a≥50%reduction in TSS at week 24,compared with 18.8%in the ruxolitinib arm;some patients reported improvement as early as week 4.

　　Taken together,pacritinib offers both splenic and symptomatic benefit,with preserved activity in patients with severe thrombocytopenia.Treatment decisions,including dose selection and monitoring,should be individualized by a treating specialist based on blood counts,concomitant medications,and patient-specific risk factors.