title: Safety and efficacy of ruxolitinib in an open-label, multicenter, single-arm phase 3b expanded-access study in patients with myelofibrosis: a snapshot of 1144 patients in the JUMP trial.
abstract: JUMP is a phase 3b expanded-access trial for patients without access to ruxolitinib outside of a clinical study; it is the largest clinical trial to date in patients with myelofibrosis who have been treated with ruxolitinib. Here, we present safety and efficacy findings from an analysis of 1144 patients with intermediate- or high-risk myelofibrosis, as well as a separate analysis of 163 patients with intermediate-1-risk myelofibrosis - a population of patients not included in the phase 3 COMFORT studies. Consistent with ruxolitinib's mechanism of action, the most common hematologic adverse events were anemia and thrombocytopenia, but these led to treatment discontinuation in only a few cases. The most common non-hematologic adverse events were primarily grade 1/2 and included diarrhea, pyrexia, fatigue, and asthenia. The rates of infections were low and primarily grade 1/2, and no new or unexpected infections were observed. The majority of patients achieved a ≥50% reduction from baseline in palpable spleen length. Improvements in symptoms were rapid, with approximately half of all patients experiencing clinically significant improvements, as assessed by various quality-of-life questionnaires. The safety and efficacy profile in intermediate-1-risk patients was consistent with that in the overall JUMP population and with that previously reported in intermediate-2- and high-risk patients. Overall, ruxolitinib provided clinically meaningful reductions in spleen length and symptoms in patients with myelofibrosis, including those with intermediate-1-risk disease, with a safety and efficacy profile consistent with that observed in the phase 3 COMFORT studies. This trial was registered as NCT01493414 at ClinicalTrials.gov.
authors.affiliation: University Hospital of Leipzig, Germany alah@medizin.uni-leipzig.de.
authors.forename: Haifa Kathrin
authors.initials: HK
authors.lastname: Al-Ali
authors.affiliation: Johannes-Wesling Academic Medical Center, University of Hannover Teaching Hospital, Minden, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Griesshammer
authors.affiliation: Charité - Universitätsmedizin Berlin, Germany.
authors.forename: Philipp
authors.initials: P
authors.lastname: le Coutre
authors.affiliation: Department of Medicine I: Hematology and Oncology, University Hospital Freiburg, Germany.
authors.forename: Cornelius F
authors.initials: CF
authors.lastname: Waller
authors.affiliation: University of Perugia, Azienda Ospedaliera S. Maria, Terni, Italy.
authors.forename: Anna Marina
authors.initials: AM
authors.lastname: Liberati
authors.affiliation: Department of Internal Medicine II, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Philippe
authors.initials: P
authors.lastname: Schafhausen
authors.affiliation: Universidade Federal de Goiania, Goiás, Brazil.
authors.forename: Renato
authors.initials: R
authors.lastname: Tavares
authors.affiliation: Miguel Servet University Hospital. IIS Aragon and Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Zaragoza, Spain.
authors.forename: Pilar
authors.initials: P
authors.lastname: Giraldo
authors.affiliation: St. Paul's Hospital, University of British Columbia, Vancouver, BC, Canada.
authors.forename: Lynda
authors.initials: L
authors.lastname: Foltz
authors.affiliation: Rabin Medical Center, Petah Tikva, Israel.
authors.forename: Pia
authors.initials: P
authors.lastname: Raanani
authors.affiliation: Princess Margaret Cancer Centre, Toronto, ON, Canada.
authors.forename: Vikas
authors.initials: V
authors.lastname: Gupta
authors.affiliation: Novartis Pharma AG, Basel, Switzerland.
authors.forename: Bayane
authors.initials: B
authors.lastname: Tannir
authors.affiliation: Novartis Pharma AG, Basel, Switzerland.
authors.forename: Julian Perez
authors.initials: JP
authors.lastname: Ronco
authors.affiliation: Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA.
authors.forename: Jagannath
authors.initials: J
authors.lastname: Ghosh
authors.affiliation: Azienda Ospedaliera Bianchi Melacrino Morelli, Reggio Calabria, Italy.
authors.forename: Bruno
authors.initials: B
authors.lastname: Martino
authors.affiliation: University of Florence, Italy.
authors.forename: Alessandro M
authors.initials: AM
authors.lastname: Vannucchi
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers; D005260:Female; D006454:Hemoglobins; D006801:Humans; D053612:Janus Kinases / Q000037:antagonists & inhibitors; D008297:Male; D008875:Middle Aged; D009570:Nitriles; D010641:Phenotype; D010976:Platelet Count; D055728:Primary Myelofibrosis / Q000175:diagnosis / Q000188:drug therapy*; 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; D011788:Quality of Life; D019233:Retreatment; D013154:Spleen / Q000473:pathology; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D015415:Biomarkers; D006454:Hemoglobins; D009570:Nitriles; D047428:Protein Kinase Inhibitors; D011720:Pyrazoles; D011743:Pyrimidines; C540383:ruxolitinib; D053612:Janus Kinases