In patients with
polycythemia vera (PV), an elevated JAK2 p.V617F allele burden is associated with indicators of more severe disease (e.g.,
leukocytosis,
splenomegaly, and increased
thrombosis risk); however, correlations between allele burden reductions and clinical benefit in patients with PV have not been extensively evaluated in a randomized trial. This exploratory analysis from the multicenter, open-label, phase 3 Randomized Study of Efficacy and Safety in
Polycythemia Vera With
JAK Inhibitor INCB018424 Versus Best Supportive Care trial evaluated the long-term effect of
ruxolitinib treatment on JAK2 p.V617F allele burden in patients with PV. Evaluable JAK2 p.V617F-positive patients randomized to
ruxolitinib (n = 107) or best available
therapy (BAT) who crossed over to
ruxolitinib at week 32 (n = 97) had consistent JAK2 p.V617F allele burden reductions throughout the study. At all time points measured (up to weeks 208 [
ruxolitinib-randomized] and 176 [
ruxolitinib crossover]), mean changes from baseline over time in JAK2 p.V617F allele burden ranged from -12.2 to -40.0% (
ruxolitinib-randomized) and -6.3 to -17.8% (
ruxolitinib crossover). Complete or partial molecular response was observed in 3 patients (
ruxolitinib-randomized, n = 2;
ruxolitinib crossover, n = 1) and 54 patients (
ruxolitinib-randomized, n = 33;
ruxolitinib crossover, n = 20; BAT, n = 1), respectively. Among patients treated with
interferon as BAT (n = 13), the mean maximal reduction in allele burden from baseline was 25.6% after crossover to
ruxolitinib versus 6.6% before crossover. Collectively, the data from this exploratory analysis suggest that
ruxolitinib treatment for up to 4 years provides progressive reductions in JAK2 p.V617F allele burden in patients with PV who are resistant to or intolerant of
hydroxyurea. The relationship between allele burden changes and clinical outcomes in patients with PV remains unclear.