Comparative Analysis of Major Polycythemia Vera Clinical Trials: PROUD-PV, MAJIC-PV, RESPONSE, and CYTO-PV
Panelists discuss how multiple pivotal clinical trials inform polycythemia vera management strategies, highlighting key findings from CYTO-PV (strict hematocrit control <45% reduces thrombosis risk fourfold), RESPONSE (ruxolitinib’s superiority over best available therapy for controlling both hematocrit and splenomegaly), MAJIC-PV (demonstrating improved event-free survival with ruxolitinib), and PROUD-PV/CONTINUATION-PV (showing ropeginterferon’s durable molecular responses compared with hydroxyurea’s diminishing effect over time).
Summary of Clinical Trials Guiding Polycythemia Vera Management
Key Clinical Trials
- CYTO-PV Study:
- 365 randomized patients comparing strict (<45%) vs lenient (45%-50%) hematocrit control
- Results: 4-fold higher risk of cardiovascular death and thrombosis with lenient control
- Key finding: Just a 3% difference in hematocrit targets led to significantly worse outcomes
- Established the importance of maintaining hematocrit <45% consistently
- RESPONSE Trial:
- Phase 3 study of ruxolitinib vs best available therapy (mostly hydroxyurea) in hydroxyurea-resistant/intolerant polycythemia vera patients requiring phlebotomies
- All patients had splenomegaly
- Results: 21% vs 1% achieved composite response (hematocrit control plus ≥35% spleen volume reduction)
- Higher individual rates of hematocrit control and spleen response with ruxolitinib
- MAJIC-PV Study (2023):
- Similar population to RESPONSE: hydroxyurea-resistant/intolerant PV requiring phlebotomies
- Key difference: No crossover allowed between arms
- Results:
- 39% complete response rate with ruxolitinib
- Improved event-free survival with ruxolitinib vs hydroxyurea
- Molecular responses correlated with clinical outcomes
- Key finding: Early switch to ruxolitinib in hydroxyurea-resistant/intolerant patients is beneficial
- PROUD-PV/CONTINUATION-PV:
- Patients diagnosed with PV within 3 years
- Ropeginterferon alfa-2b vs hydroxyurea
- Results:
- Similar complete hematologic response at 12 months
- Long-term outcomes favored ropeginterferon
- Molecular responses with hydroxyurea diminished over time while ropeginterferon responses deepened
Clinical Implications
- The critical importance of maintaining hematocrit <45% is strongly supported by evidence
- For hydroxyurea-resistant/intolerant patients, early switch to ruxolitinib improves outcomes
- Ropeginterferon offers superior long-term molecular responses compared with hydroxyurea
- Clinical and molecular response correlations suggest value in monitoring both parameters
These trial results provide a data-driven framework for risk-adapted management of polycythemia vera patients, supporting the treatment algorithm presented earlier and highlighting the importance of prompt recognition and management of hydroxyurea resistance or intolerance.
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