MAJIC-PV trial update: Clinical benefit of ruxolitinib for the treatment of PV

The phase II MAJIC-PV trial (ISRCTN61925716) confirmed the clinical benefit of ruxolitinib treatment versus best available therapy (BAT) for patients diagnosed with polycythemia vera (PV) that is hydroxycarbamide intolerant or resistant.¹

For previous updates on this study from the 64th American Society of Hematology (ASH) Annual Meeting and Exposition and other phase I/II trials investigating JAK inhibition, read our recent article here.

Study design¹

• A total of 190 patients were enrolled between August 2012 and August 2016.
  • 180 patients were then randomized to receive ruxolitinib (n = 93) or BAT (n = 87).
• Patients were required to be ≥18 years old, diagnosed with high-risk PV, and be intolerant or resistant to hydroxycarbamide.
•  Patients received 10 mg of ruxolitinib twice daily.
  • Patients with platelet counts between 100 × 10⁹/L and 200 × 10⁹/L received 5 mg ruxolitinib twice daily.
• The primary endpoint for the trial was complete response, defined as:
  • hematocrit levels <45% without venesection for 3 months;
  • platelet counts ≤400 × 10⁹/L;
  • white blood cell counts ≤10 × 10⁹/L; and
  • normal spleen size.

Efficacy¹

• The median age of patients was 66 years.
• In total, 30%, 44%, and 26% of patients were resistant to, intolerant to, or both resistant and intolerant to hydroxycarbamide, respectively.
• The median durations of ruxolitinib and BAT treatments were 1,568 days and 1,220 days, respectively.
• The overall response rates for the ruxolitinib and BAT groups were 97% and 93%, respectively.
  • 54% of patients on ruxolitinib achieved a best response of partial response compared with 67% of patients on BAT.
• A total of 83 venesections were recorded in the ruxolitinib arm compared with 307 in the BAT arm.
• Ruxolitinib therapy significantly improved thromboembolic event-free survival (EFS) but not hemorrhage-free EFS (p < 0.001).
• The ruxolitinib group had a 3-year progression-free survival rate of 84% vs 75% for BAT.
• The ruxolitinib group had a 3-year overall survival rate of 88% vs 87% for BAT.
• At median follow-ups of 48 months and 36 months, 56% and 25% of evaluable patients in the ruxolitinib and BAT arms, respectively, achieved a >50% variant allele fraction reduction (p < 0.001).
• The median time to molecular response for ruxolitinib treatment was 36 months.
  • Median time was not reached for BAT.
• Patients with additional driver mutations had a poorer EFS (p = 0.01).
• The mean total symptom score was 52 months in the ruxolitinib arm.
  • Patients in the BAT arm experienced worsened symptom burden but improved to baseline at 56 months.
• Of evaluable patients, 61% and 30% of those in the ruxolitinib and BAT arms, respectively, had a ≥50% total symptom score reduction at one or more time points (p = 0.001).

Safety¹

• The most common adverse effects were gastrointestinal disorders, infections, and vascular disorders.
• A total of 27 Grade 3/4 infection events occurred in the ruxolitinib arm compared with 12 events in the BAT arm.
• There were no deaths due to infection.
• Squamous cell carcinoma was reported in 11 patients treated with ruxolitinib.

Conclusion

Results from the trial highlight that ruxolitinib treatment is associated with improved efficacy, hematologic control, and symptom responses for patients with PV compared with BAT. The safety profile is consistent with previous findings.