title: Which patients with myelofibrosis should receive ruxolitinib therapy? ELN-SIE evidence-based recommendations.
abstract: Ruxolitinib is an oral Janus-activated kinase 1 (JAK1)/JAK2 inhibitor approved for the treatment of patients with myelofibrosis based on the results of two randomized clinical trials. However, discordant indications were provided by regulatory agencies and scientific societies for selecting the most appropriate candidates to this drug. The European LeukemiaNet and the Italian Society of Hematology shared the aim of building evidence-based recommendations for the use of ruxolitinib according to the GRADE methodology. Eighteen patient-intervention-comparator-outcome profiles were listed, each of them comparing ruxolitinib to other therapies with the aim of improving one of the three clinical outcomes: (a) splenomegaly, (b) disease-related symptoms, and (c) survival. Ruxolitinib was strongly recommended for improving symptomatic or severe (>15 cm below the costal margin) splenomegaly in patients with an International Prognostic Scoring System (IPSS)/dynamic IPSS risk intermediate 2 or high. Ruxolitinib was also strongly recommended for improving systemic symptoms in patients with an MPN10 score >44, refractory severe itching, unintended weight loss not attributable to other causes or unexplained fever. Because of weak evidence, the panel does not recommend ruxolitinib therapy for improving survival. Also, the recommendations given above do not necessarily apply to patients who are candidates for allogeneic stem cell transplant.
authors.affiliation: Ospedale Cardinal Massaia, Asti, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Marchetti
authors.affiliation: IRCCS Policlinico San Matteo Foundation, Pavia, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Barosi
authors.affiliation: Hospital Clinic, IDIBAPS, Barcelona, Spain.
authors.forename: F
authors.initials: F
authors.lastname: Cervantes
authors.affiliation: Uppsala University Hospital, Uppsala, Sweden.
authors.forename: G
authors.initials: G
authors.lastname: Birgegård
authors.affiliation: Johannes Wesling Klinikum Minden, Minden, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Griesshammer
authors.affiliation: Guy's and St Thomas' NHS Foundation, London, UK.
authors.forename: C
authors.initials: C
authors.lastname: Harrison
authors.affiliation: Medizinische Fakultät Mannheim, Universität Heidelberg, Mannheim, Germany.
authors.forename: R
authors.initials: R
authors.lastname: Hehlmann
authors.affiliation: Centre d'Investigations Cliniques - CIC 1427, Paris, France.
authors.forename: J-J
authors.initials: JJ
authors.lastname: Kiladjian
authors.affiliation: University Hospital Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: N
authors.initials: N
authors.lastname: Kröger
authors.affiliation: Queen's University Belfast, Belfast, UK.
authors.forename: M F
authors.initials: MF
authors.lastname: McMullin
authors.affiliation: Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy.
authors.forename: F
authors.initials: F
authors.lastname: Passamonti
authors.affiliation: Ospedale di Circolo e Fondazione Macchi, Varese, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Vannucchi
authors.affiliation: Research Foundation, Ospedale Papa Giovanni XXIII, Bergamo, Italy.
authors.forename: T
authors.initials: T
authors.lastname: Barbui
mesh_terms: D015897:Comorbidity; D006470:Hemorrhage / Q000209:etiology; D006801:Humans; D006975:Hypertension, Portal / Q000209:etiology; D007239:Infections / Q000209:etiology; D053613:Janus Kinase 1 / Q000037:antagonists & inhibitors; D053614:Janus Kinase 2 / Q000037:antagonists & inhibitors; D058990:Molecular Targeted Therapy; D009570:Nitriles; D010641:Phenotype; D055728:Primary Myelofibrosis / Q000175:diagnosis / Q000188:drug therapy* / Q000378:metabolism / Q000401:mortality; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D011720:Pyrazoles / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D011743:Pyrimidines; D013163:Splenomegaly; D016896:Treatment Outcome
chemical_list: D009570:Nitriles; D047428:Protein Kinase Inhibitors; D011720:Pyrazoles; D011743:Pyrimidines; C540383:ruxolitinib; D053613:Janus Kinase 1; D053614:Janus Kinase 2