MAJIC-PV Trial Outcomes: Guiding Treatment Decisions for Hydroxyurea-Resistant Polycythemia Vera

Summary of MAJIC-PV Trial: Implications for Ruxolitinib in Polycythemia Vera

Key Findings from MAJIC-PV

• Event-free survival data: For the first time, demonstrated approximately 40% risk reduction with ruxolitinib vs hydroxyurea in resistant/intolerant patients
• Thrombosis-free survival: Similarly showed approximately 40% risk reduction

Clinical Significance

• Addresses critical knowledge gap: Previous data established hematocrit control, symptom and spleen benefits, but thrombotic outcome benefits were unproven
• Reinforces need for prompt therapy change when hydroxyurea resistance develops

Disease-Modifying Potential

• Molecular response correlation:
  • JAK2 V617F allele burden reduction observed with ruxolitinib
  • Allele burden decrease correlated with:
    • Improvement in blood counts
    • Enhanced event-free survival
  • Challenges perception that ruxolitinib merely provides symptomatic relief (“just a bandage”)
  • Suggests potential disease-modifying effects

Comprehensive Hematologic Control

• Multilineage benefits:
  • Complete hematologic response includes normalization of all 3 cell lines
  • Platelet count normalization may contribute to long-term benefits
  • Suggests treating beyond just hematocrit control

The MAJIC-PV data transforms the understanding of ruxolitinib’s role in PV management by confirming its ability to reduce thrombotic events—the primary goal of polycythemia vera therapy—while also suggesting disease-modifying potential through reduction of the malignant clone burden.