title: Ruxolitinib for symptom control in patients with chronic lymphocytic leukaemia: a single-group, phase 2 trial.
abstract: BACKGROUND
  Disease-related symptoms impair the quality of life of patients with chronic lymphocytic leukaemia (CLL) who do not require systemic therapy. Available therapies are not specifically aimed at symptom control. Because stimulation of the B-cell receptor activates JAK2 in CLL cells and the JAK2 inhibitor ruxolitinib improves symptoms in patients with myelofibrosis, we postulated that ruxolitinib would improve disease-related symptoms in patients with CLL. We did a phase 2 trial of ruxolitinib to test this hypothesis.
  
  
  METHODS
  Symptomatic patients with CLL who did not require systemic therapy were enrolled at MD Anderson Cancer Center (Houston, TX, USA) between Sept 15, 2014, and Sept 20, 2015. Participants were given 10 mg ruxolitinib orally twice a day. Scores on the Brief Fatigue Inventory (BFI), CLL module of the MD Anderson Symptom Inventory (MDASI) and symptom-associated interference in daily activities, were assessed before treatment and after 3 months. This trial is ongoing and is registered at ClinicalTrials.gov (NCT02131584).
  
  
  RESULTS
  41 patients (25 previously untreated for CLL and 16 previously treated) were enrolled. At 3 months, the mean percentage change from baseline in BFI score was 44·3% (SD 35·0, p<0·0001), in symptom interference score was 43·4% (51·5, p<0·0001), and in MDASI score was 42·1% (37·4, p<0·0001). 32 (78%) of the patients experienced 20% or greater reduction in the mean BFI, and 24 (59%) had a reduction of two units or more in worst fatigue score in past 24 hours as assessed by the BFI. The most comment grade 3-4 adverse events were neutropenia (n=2 [5%]), hypertension (n=2 [5%]), insomnia (n=1 [2%]), tinnitus and dizziness (n=1 [2%]), and thrombocytopenia (n=1 [2%]).
  
  
  CONCLUSIONS
  In patients with CLL, ruxolitinib was associated with significant improvements in disease-related symptoms as measured by BFI, MDASI, and symptom interference scores. Further studies to test the therapeutic efficacy of ruxolitinib in CLL are warranted.
  
  
  BACKGROUND
  Incyte, National Cancer Institute.
authors.affiliation: Departments of Leukemia, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Preetesh
authors.initials: P
authors.lastname: Jain
authors.affiliation: Departments of Leukemia, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Keating
authors.affiliation: Departments of Leukemia, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Sarah
authors.initials: S
authors.lastname: Renner
authors.affiliation: Symptom Research, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Charles
authors.initials: C
authors.lastname: Cleeland
authors.affiliation: Biostatistics, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Huang
authors.initials: H
authors.lastname: Xuelin
authors.affiliation: Biostatistics, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Graciela Nogueras
authors.initials: GN
authors.lastname: Gonzalez
authors.affiliation: Departments of Leukemia, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: David
authors.initials: D
authors.lastname: Harris
authors.affiliation: Departments of Leukemia, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Ping
authors.initials: P
authors.lastname: Li
authors.affiliation: Departments of Leukemia, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Zhiming
authors.initials: Z
authors.lastname: Liu
authors.affiliation: Departments of Leukemia, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Ivo
authors.initials: I
authors.lastname: Veletic
authors.affiliation: Departments of Leukemia, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Uri
authors.initials: U
authors.lastname: Rozovski
authors.affiliation: Departments of Leukemia, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Nitin
authors.initials: N
authors.lastname: Jain
authors.affiliation: Departments of Leukemia, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Phillip
authors.initials: P
authors.lastname: Thompson
authors.affiliation: Departments of Leukemia, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Prithviraj
authors.initials: P
authors.lastname: Bose
authors.affiliation: Departments of Leukemia, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Courtney
authors.initials: C
authors.lastname: DiNardo
authors.affiliation: Departments of Leukemia, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Ferrajoli
authors.affiliation: Departments of Leukemia, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Susan
authors.initials: S
authors.lastname: O'Brien
authors.affiliation: Departments of Leukemia, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Jan
authors.initials: J
authors.lastname: Burger
authors.affiliation: Departments of Leukemia, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: William
authors.initials: W
authors.lastname: Wierda
authors.affiliation: Departments of Leukemia, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Srdan
authors.initials: S
authors.lastname: Verstovsek
authors.affiliation: Departments of Leukemia, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Hagop
authors.initials: H
authors.lastname: Kantarjian
authors.affiliation: Departments of Leukemia, University of Texas MD Anderson Cancer Center, Houston, TX, USA. Electronic address: zestrov@mdanderson.org.
authors.forename: Zeev
authors.initials: Z
authors.lastname: Estrov
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D005221:Fatigue; D005260:Female; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D011788:Quality of Life; D000069283:Rituximab / Q000009:adverse effects / Q000627:therapeutic use*
chemical_list: D000970:Antineoplastic Agents; D000069283:Rituximab