Clinical Decision-Making With PERSIST-2: Optimizing Therapy for Anemic Myelofibrosis Patients With Splenomegaly

Summary of Pacritinib in Thrombocytopenic Myelofibrosis Patients

PERSIST-2 Trial: Key Findings

• Pivotal data: Led to FDA approval of pacritinib for MF patients with platelets <50,000/μL
• Spleen response: 29% SVR35 rate with pacritinib vs 3% in control arm (approximately 10-fold improvement)
• Comparative benefit: Control arm included patients on ruxolitinib, suggesting superior efficacy of pacritinib in thrombocytopenic patients

Anemia Benefits

• Unexpected finding: Anemia improvement was not initially anticipated but emerged as a significant benefit
• Potential mechanism: Likely related to ACVR1 inhibition, possibly combined with IRAK1 pathway effects
• Clinical observations: Some patients achieve transfusion independence

Clinical Application

• Patient counseling approach:
  • Setting realistic expectations about transfusion burden reduction rather than promising complete independence
  • Goals include: fewer transfusions, reduced infusion center visits, delayed iron overload
  • While platelet count increases may occur, clinicians should set expectations for platelet stabilization rather than improvement
• Key advantage: Ability to deliver effective JAK2 inhibition for spleen and symptom benefits in severely thrombocytopenic patients while maintaining stable platelet counts

The panel emphasized that pacritinib offers a unique therapeutic option for the challenging bicytopenic myelofibrosis patient population (thrombocytopenia plus anemia), addressing a significant unmet need in myelofibrosis management.