title: Markers of iron deficiency in patients with polycythemia vera receiving ruxolitinib or best available therapy.
abstract: 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.
authors.affiliation: University of Texas MD Anderson Cancer Center, Houston, TX, USA. Electronic address: sverstov@mdanderson.org.
authors.forename: Srdan
authors.initials: S
authors.lastname: Verstovsek
authors.affiliation: Guy's and St. Thomas NHS Foundation Trust, London, UK.
authors.forename: Claire N
authors.initials: CN
authors.lastname: Harrison
authors.affiliation: Centre d'Investigations Cliniques (INSERM CIC 1427), APHP, Hôpital Saint-Louis, INSERM and Université Paris Diderot, Paris, France.
authors.forename: Jean-Jacques
authors.initials: JJ
authors.lastname: Kiladjian
authors.affiliation: Saint Agnes Cancer Institute, Baltimore, MD, USA.
authors.forename: Carole
authors.initials: C
authors.lastname: Miller
authors.affiliation: Incyte Corporation, Wilmington, DE, USA.
authors.forename: Ahmad B
authors.initials: AB
authors.lastname: Naim
authors.affiliation: Incyte Corporation, Wilmington, DE, USA.
authors.forename: Dilan C
authors.initials: DC
authors.lastname: Paranagama
authors.affiliation: Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA.
authors.forename: Dany
authors.initials: D
authors.lastname: Habr
authors.affiliation: CRIMM-Center of Research and Innovation for Myeloproliferative Neoplasms, AOU Careggi and University of Florence, Florence, Italy.
authors.forename: Alessandro M
authors.initials: AM
authors.lastname: Vannucchi
mesh_terms: D015415:Biomarkers / Q000097:blood; D005260:Female; D006801:Humans; D000090463:Iron Deficiencies; D008297:Male; D008875:Middle Aged; D009570:Nitriles; D011087:Polycythemia Vera / Q000188:drug therapy*; D011446:Prospective Studies; D011720:Pyrazoles / Q000494:pharmacology / Q000627:therapeutic use*; D011743:Pyrimidines; D016896:Treatment Outcome
chemical_list: D015415:Biomarkers; D009570:Nitriles; D011720:Pyrazoles; D011743:Pyrimidines; C540383:ruxolitinib
keywords: Iron deficiency; JAK2; Janus kinase 2; Polycythemia vera; Ruxolitinib