TY - JOUR
T1 - Ruxolitinib for symptom control in patients with chronic lymphocytic leukaemia
T2 - a single-group, phase 2 trial
AU - Jain, Preetesh
AU - Keating, Michael
AU - Renner, Sarah
AU - Cleeland, Charles
AU - Xuelin, Huang
AU - Gonzalez, Graciela Nogueras
AU - Harris, David
AU - Li, Ping
AU - Liu, Zhiming
AU - Veletic, Ivo
AU - Rozovski, Uri
AU - Jain, Nitin
AU - Thompson, Phillip
AU - Bose, Prithviraj
AU - DiNardo, Courtney
AU - Ferrajoli, Alessandra
AU - O'Brien, Susan
AU - Burger, Jan
AU - Wierda, William
AU - Verstovsek, Srdan
AU - Kantarjian, Hagop
AU - Estrov, Zeev
N1 - Publisher Copyright:
© 2017 Elsevier Ltd
PY - 2017/2/1
Y1 - 2017/2/1
N2 - 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). Findings 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%]). Interpretation 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. Funding Incyte, National Cancer Institute.
AB - 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). Findings 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%]). Interpretation 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. Funding Incyte, National Cancer Institute.
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U2 - 10.1016/S2352-3026(16)30194-6
DO - 10.1016/S2352-3026(16)30194-6
M3 - Article
C2 - 28089238
AN - SCOPUS:85009454823
SN - 2352-3026
VL - 4
SP - e67-e74
JO - The Lancet Haematology
JF - The Lancet Haematology
IS - 2
ER -