Ruxolitinib for symptom control in patients with chronic lymphocytic leukaemia: a single-group, phase 2 trial

Preetesh Jain, Michael Keating, Sarah Renner, Charles Cleeland, Huang Xuelin, Graciela Nogueras Gonzalez, David Harris, Ping Li, Zhiming Liu, Ivo Veletic, Uri Rozovski, Nitin Jain, Phillip Thompson, Prithviraj Bose, Courtney DiNardo, Alessandra Ferrajoli, Susan O'Brien, Jan Burger, William Wierda, Srdan Verstovsek, Hagop Kantarjian, Zeev Estrov, Preetesh Jain, Michael Keating, Sarah Renner, Charles Cleeland, Huang Xuelin, Graciela Nogueras Gonzalez, David Harris, Ping Li, Zhiming Liu, Ivo Veletic, Uri Rozovski, Nitin Jain, Phillip Thompson, Prithviraj Bose, Courtney DiNardo, Alessandra Ferrajoli, Susan O'Brien, Jan Burger, William Wierda, Srdan Verstovsek, Hagop Kantarjian, Zeev Estrov

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).

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.

Conflict of interest statement

Conflicts-of-Interest Disclosure: Z.E. receives research support from and serves as a consultant to Incyte Corporation. None of the other authors have any conflicts of interest to disclose.

Copyright © 2017 Elsevier Ltd. All rights reserved.

Figures

Figure 1. (A-B). Ruxolitinib treatment reduces symptom…
Figure 1. (A-B). Ruxolitinib treatment reduces symptom scores of patients with CLL
Waterfall plot showing the mean percentage change from baseline to 3-month scores on BFI (brief fatigue inventory), MDASI (CLL module of the MD Anderson symptom inventory), IS (symptom-associated interference in daily activities) and worst fatigue in 24 hours on BFI scale. Each vertical line represents an individual participant. Significant reductions in symptom scores were observed after ruxolitinib treatment (P<0.0001 in all three scoring systems). The proportion of participants with ≥20% reduction in BFI and/or MDASI score was 78% (32 of 41).
Figure 2. Ruxolitinib induced mobilization of CLL…
Figure 2. Ruxolitinib induced mobilization of CLL cells from lymph nodes to the peripheral blood
Ruxolitinib treatment increased and then decreased absolute lymphocyte counts (ALC) of CLL patients. Mean changes in peripheral blood ALC are depicted. Overall, ALC increased initially and then decreased. Previously treated participants showed a dampened response compared to previously untreated participants.

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