title: Ruxolitinib in clinical practice for primary and secondary myelofibrosis: an analysis of safety and efficacy of Gruppo Laziale of Ph-negative MPN.
abstract: Ruxolitinib, a JAK1 and JAK2 inhibitor, has been tested and approved for the treatment of primary and secondary myelofibrosis (MF). Aim of our study is to report safety and efficacy of ruxolitinib in 98 patients affected by MF treated outside clinical trials and collected and treated consecutively by the Lazio Cooperative Group for Ph negative myeloproliferative diseases.There were 45 males and 53 females; median age was 61.8 years (range 35.3-88). Forty-five patients were diagnosed as primary MF and 53 as secondary MF. Seventy-seven patients (78.5%) experienced constitutional symptoms at baseline, and out of 94 patients tested, 66 (70%) were JAK2V617Fmutated. Overall, 40 patients received hydroxyurea as firstline treatment, 30 patients received other chemotherapeutic approaches, whereas 28 were treated with ruxolitinib frontline. Median time from diagnosis to start of ruxolitinib in the whole cohort was 34.6 months. Fifty-eight patients (59%) required a dose reduction during the first 3 months due to hematological toxicity in the majority of cases. At 48 weeks, 52% of patients obtained a clinical benefit: of them 7 patients (7%) had a CR, 10 (10%) a PR, 6 patients (6%) a CI, and 28 patients (28.5%) a spleen response. Overall, 66% of patients had disappearance of baseline symptoms burden. After 1 year, of 72 evaluable patients, 52% achieved and maintained a clinical benefit. Adverse events of special interest at any grade included anemia (39.7%), thrombocytopenia (25.5%), infections (16.3%, of which 10 were bronchopneumonia), fluid retention (3%), diarrhea (2%) and abdominal pain (2%). After a median follow-up of 16 months from start of ruxolitinib, median daily dose decreased to 10 mg BID and 21 patients (21%) discontinued the drug. The results of this retrospective multicentric analysis confirmed the efficacy of ruxolitinib outside clinical trials with more than half of treated patients achieving and maintaining a clinical benefit and most of them reporting relief from symptoms.
authors.affiliation: Department of Cellular Biotechnologies and Hematology, Sapienza University, Via Benevento 6, 00161, Rome, Italy. breccia@bce.uniroma1.it.|Azienda Policlinico Umberto 1-Sapienza University, Rome, Italy. breccia@bce.uniroma1.it.
authors.forename: Massimo
authors.initials: M
authors.lastname: Breccia
authors.affiliation: Hematology, Nuovo Regina Margherita Hospital, Rome, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Andriani
authors.affiliation: Hematology, Belcolle Hospital, Viterbo, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Montanaro
authors.affiliation: Hematology, S. Eugenio Hospital, Rome, Italy.
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Abruzzese
authors.affiliation: Tor Vergata University, Rome, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Buccisano
authors.affiliation: Hematology, S. Giovanni Hospital, Rome, Italy.
authors.forename: Michele
authors.initials: M
authors.lastname: Cedrone
authors.affiliation: Hematology, S. Maria Goretti Hospital, Latina, Italy.
authors.forename: Antonietta
authors.initials: A
authors.lastname: Centra
authors.affiliation: Hematology, Nuovo Regina Margherita Hospital, Rome, Italy.
authors.forename: Nicoletta
authors.initials: N
authors.lastname: Villivà
authors.affiliation: Hematology, Belcolle Hospital, Viterbo, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Celesti
authors.affiliation: Hematology, S. Eugenio Hospital, Rome, Italy.
authors.forename: Malgorzata Monica
authors.initials: MM
authors.lastname: Trawinska
authors.affiliation: Azienda Policlinico Umberto 1-Sapienza University, Rome, Italy.
authors.forename: Fulvio
authors.initials: F
authors.lastname: Massaro
authors.affiliation: Tor Vergata University, Rome, Italy.
authors.forename: Ambra
authors.initials: A
authors.lastname: Di Veroli
authors.affiliation: Hematology, S. Giovanni Hospital, Rome, Italy.
authors.forename: Barbara
authors.initials: B
authors.lastname: Anaclerico
authors.affiliation: Azienda Policlinico Umberto 1-Sapienza University, Rome, Italy.
authors.forename: Gioia
authors.initials: G
authors.lastname: Colafigli
authors.affiliation: Azienda Policlinico Umberto 1-Sapienza University, Rome, Italy.
authors.forename: Matteo
authors.initials: M
authors.lastname: Molica
authors.affiliation: Hematology and Stem Cell Transplantation Unit, Regina Elena National Cancer Institute, Rome, Italy.
authors.forename: Antonio
authors.initials: A
authors.lastname: Spadea
authors.affiliation: Hematology, Fabrizio Spaziani Hospital, Frosinone, Italy.
authors.forename: Luca
authors.initials: L
authors.lastname: Petriccione
authors.affiliation: Hematology, S. Maria Goretti Hospital, Latina, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Cimino
authors.affiliation: Azienda Policlinico Umberto 1-Sapienza University, Rome, Italy.
authors.forename: Roberto
authors.initials: R
authors.lastname: Latagliata
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015331:Cohort Studies; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007558:Italy / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D009196:Myeloproliferative Disorders / Q000175:diagnosis / Q000188:drug therapy / Q000453:epidemiology; D009570:Nitriles; D055728:Primary Myelofibrosis / Q000175:diagnosis* / Q000188:drug therapy* / Q000453:epidemiology; D011720:Pyrazoles / Q000627:therapeutic use*; D011743:Pyrimidines; D012189:Retrospective Studies; D016896:Treatment Outcome
chemical_list: D009570:Nitriles; D011720:Pyrazoles; D011743:Pyrimidines; C540383:ruxolitinib
keywords: Myelofibrosis; Outcome; Response rate; Ruxolitinib