Polycythemia vera (PV) is characterized by erythropoiesis and JAK2-activating mutations, with increased risks of morbidity and mortality. Most patients with PV are
iron deficient, and treatment often includes hematocrit control with phlebotomy, which may exacerbate
iron deficiency-associated complications. The phase 3 RESPONSE trial evaluated the JAK1/JAK2 inhibitor
ruxolitinib (n=110) versus best available
therapy (BAT; n=112) in patients with PV who were
hydroxyurea-resistant/intolerant.
Ruxolitinib was superior to BAT for hematocrit control, reduction in
splenomegaly, and blood count normalization. This exploratory analysis, the first to evaluate
iron status in a prospective study of patients with PV, investigated
ruxolitinib effects on 7 serum
iron markers and
iron deficiency-related patient-reported outcomes (PRO). Among patients with evidence of baseline
iron deficiency,
ruxolitinib was associated with normalization of
iron marker levels, compared with lesser improvement with BAT.
Iron levels remained stable in
ruxolitinib patients with normal
iron levels at baseline. Regardless of baseline
iron status, treatment with
ruxolitinib was associated with improvements in concentration problems, cognitive function,
dizziness,
fatigue,
headaches, and inactivity, although improvements were generally greater among patients with baseline
iron deficiency. The improvements in
iron deficiency markers and PROs observed with
ruxolitinib are suggestive of clinical benefits that warrant further exploration.