title: The use of erythropoiesis-stimulating agents with ruxolitinib in patients with myelofibrosis in COMFORT-II: an open-label, phase 3 study assessing efficacy and safety of ruxolitinib versus best available therapy in the treatment of myelofibrosis.
abstract: BACKGROUND
  Anemia is considered a negative prognostic risk factor for survival in patients with myelofibrosis. Most patients with myelofibrosis are anemic, and 35-54 % present with anemia at diagnosis. Ruxolitinib, a potent inhibitor of Janus kinase (JAK) 1 and JAK2, was associated with an overall survival benefit and improvements in splenomegaly and patient-reported outcomes in patients with myelofibrosis in the two phase 3 COMFORT studies. Consistent with the ruxolitinib mechanism of action, anemia was a frequently reported adverse event. In clinical practice, anemia is sometimes managed with erythropoiesis-stimulating agents (ESAs). This post hoc analysis evaluated the safety and efficacy of concomitant ruxolitinib and ESA administration in patients enrolled in COMFORT-II, an open-label, phase 3 study comparing the efficacy and safety of ruxolitinib with best available therapy for treatment of myelofibrosis. Patients were randomized (2:1) to receive ruxolitinib 15 or 20 mg twice daily or best available therapy. Spleen volume was assessed by magnetic resonance imaging or computed tomography scan.
  
  
  RESULTS
  Thirteen of 146 ruxolitinib-treated patients had concomitant ESA administration (+ESA). The median exposure to ruxolitinib was 114 weeks in the +ESA group and 111 weeks in the overall ruxolitinib arm; the median ruxolitinib dose intensity was 33 mg/day for each group. Six weeks before the first ESA administration, 10 of the 13 patients had grade 3/4 hemoglobin abnormalities. These had improved to grade 2 in 7 of the 13 patients by 6 weeks after the first ESA administration. The rate of packed red blood cell transfusions per month within 12 weeks before and after first ESA administration remained the same in 1 patient, decreased in 2 patients, and increased in 3 patients; 7 patients remained transfusion independent. Reductions in splenomegaly were observed in 69 % of evaluable patients (9/13) following first ESA administration.
  
  
  CONCLUSIONS
  Concomitant use of an ESA with ruxolitinib was well tolerated and did not affect the efficacy of ruxolitinib. Further investigations evaluating the effects of ESAs to alleviate anemia in ruxolitinib-treated patients are warranted (ClinicalTrials.gov identifier, NCT00934544; July 6, 2009).
authors.affiliation: Center for Cancer Research and Cell Biology, Queen's University, Belfast, UK.
authors.forename: Mary Frances
authors.initials: MF
authors.lastname: McMullin
authors.affiliation: Guy's and St. Thomas' NHS Foundation Trust, London, UK.
authors.forename: Claire N
authors.initials: CN
authors.lastname: Harrison
authors.affiliation: University of Leipzig, Leipzig, Germany.
authors.forename: Dietger
authors.initials: D
authors.lastname: Niederwieser
authors.affiliation: H. Hartziekenhuis, Roeselare, Belgium.
authors.forename: Hilde
authors.initials: H
authors.lastname: Demuynck
authors.affiliation: University of Leipzig, Leipzig, Germany.
authors.forename: Nadja
authors.initials: N
authors.lastname: Jäkel
authors.affiliation: Novartis Pharma AG, Basel, Switzerland.
authors.forename: Prashanth
authors.initials: P
authors.lastname: Gopalakrishna
authors.affiliation: Novartis Pharma AG, Basel, Switzerland.
authors.forename: Mari
authors.initials: M
authors.lastname: McQuitty
authors.affiliation: Novartis Pharma AG, Basel, Switzerland.
authors.forename: Viktoriya
authors.initials: V
authors.lastname: Stalbovskaya
authors.affiliation: Institut Universitaire du Cancer de Toulouse, Université de Toulouse III, Toulouse, France.
authors.forename: Christian
authors.initials: C
authors.lastname: Recher
authors.affiliation: Limburgs Oncologisch Centrum, Hasselt, Belgium.
authors.forename: Koen
authors.initials: K
authors.lastname: Theunissen
authors.affiliation: Medical University of Vienna, Vienna, Austria.
authors.forename: Heinz
authors.initials: H
authors.lastname: Gisslinger
authors.affiliation: Hôpital Saint-Louis et Université Paris Diderot, Paris, France.
authors.forename: Jean-Jacques
authors.initials: JJ
authors.lastname: Kiladjian
authors.affiliation: University of Leipzig, Leipzig, Germany.
authors.forename: Haifa-Kathrin
authors.initials: HK
authors.lastname: Al-Ali
keywords: Anemia management; ESA; Erythropoiesis-stimulating agents; Myelofibrosis; Ruxolitinib