What are the longest term studies on ruxolitinib (Jakafi) in post-polycythemia vera myelofibrosis (post-PV MF)?

Longest-Term Studies on Ruxolitinib in Post-PV Myelofibrosis

The longest-term study on ruxolitinib in post-PV myelofibrosis is the 5-year follow-up data from the RESPONSE trial, which demonstrated sustained efficacy with a 74% probability of maintaining primary composite response at 5 years in patients with polycythemia vera, including those who progressed to post-PV myelofibrosis. 1

Evidence Base for Ruxolitinib in Post-PV MF

Ruxolitinib, an oral JAK1/JAK2 inhibitor, has been extensively studied in myeloproliferative neoplasms (MPNs), including post-PV myelofibrosis. The evidence supporting its use comes from several key studies:

Long-term Follow-up Studies

• RESPONSE trial (5-year follow-up): This phase 3 study provides the longest-term data on ruxolitinib in patients with polycythemia vera who were resistant to or intolerant of hydroxyurea, including those who progressed to post-PV MF 1

  • Demonstrated durable responses with 74% probability of maintaining primary composite response at 5 years
  • Complete hematological remission maintenance probability of 55% at 5 years
  • Overall survival probability at 5 years was 91.9% in the ruxolitinib group

• RESPONSE-2 trial (5-year follow-up): While focused on PV patients without splenomegaly, this study provides additional long-term safety and efficacy data relevant to the PV-MF disease continuum 2

  • 5-year overall survival was 96% in the ruxolitinib group
  • Sustained hematocrit control below 45% throughout the 5-year follow-up period

Efficacy in Post-PV MF

The NCCN guidelines highlight that ruxolitinib demonstrates significant benefits in post-PV MF patients, including:

• Reduction in spleen volume (≥35%) in 38% of patients 3
• Complete hematologic remission in 24% of patients 3
• Reduction in symptom burden (≥50%) in 49% of patients 3
• Lower rate of thromboembolic events compared to best available therapy (1.8% vs 8.2%) 3

Safety Profile in Long-term Treatment

Long-term ruxolitinib treatment in post-PV MF is generally well-tolerated with manageable adverse events:

• Hematologic adverse events: Anemia and thrombocytopenia are the most common hematologic toxicities 3, 1

  • Grade 3/4 anemia occurred in 2% of ruxolitinib-treated patients 3
  • Most anemia events were mild to moderate in severity 1

• Non-hematologic adverse events:

  • Herpes zoster infection occurred in 6% of ruxolitinib-treated patients 3
  • Risk of infections requires monitoring during long-term treatment 3

Important Clinical Considerations

When using ruxolitinib for post-PV MF patients:

1. Avoid abrupt discontinuation: Sudden withdrawal can provoke a shock-like syndrome due to re-emergence of suppressed inflammatory cytokines 3

2. Dose management: Optimal dosing management is critical to maintain long-term treatment benefit 4

   • Dose-dependent cytopenias can be managed with transfusions, dose reduction, or treatment interruption

3. Limited disease-modifying effect: Despite symptom improvement and spleen reduction, there is limited evidence of disease modification 3

   • Only a minority of patients show improvement in bone marrow fibrosis or reduction in JAK2 allele burden

4. Alternative for transplant-ineligible patients: While allogeneic stem cell transplantation remains the only curative approach for MF, ruxolitinib provides significant clinical benefit for transplant-ineligible patients 3

Pitfalls and Caveats

• Resistance development: Long-term efficacy may be limited by development of resistance in some patients
• Immunosuppression: Increased risk of infections, particularly herpes zoster, requires vigilance during long-term treatment
• Cytopenia management: Regular monitoring of blood counts is essential, as cytopenias may necessitate dose adjustments

Ruxolitinib remains the most extensively studied JAK inhibitor in post-PV MF with robust long-term data supporting its efficacy and safety profile over a 5-year period.