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Ruxolitinib controls disease-related symptoms in CLL
Ruxolitinib led to symptom improvement, including a reduction in fatigue, among patients with chronic lymphocytic leukemia who did not require systemic therapy, according to results of a prospective study.
“We have tried to address a very important and often neglected aspect of managing patients with CLL,” Preetesh Jain, MBBS, MD, DM, PhD, from the department of leukemia at The University of Texas MD Cancer Center, told HemOnc Today. “Adequate control of symptoms has not been a focus of clinical studies reported in patients with CLL.”
Ruxolitinib (Jakafi, Incyte) has shown improvement of symptoms in patients with myelofibrosis, and it was associated with improvement of symptoms and decreased concentrations of inflammatory biomarkers in patients with steroid-refractory graft-versus-host disease or pancreatic cancer.
In this phase 2 clinical trial, the researchers evaluated wither ruxolitinib conferred any relief in CLL symptoms. Researchers enrolled 41 patients — including 25 who were previously untreated and 16 who were previously treated for CLL — from MD Anderson Cancer Center. Patients received 10 mg ruxolitinib orally twice per day, with potential for dose adjustment.
Researchers assessed symptoms before treatment and at 3 months using the Brief Fatigue Inventory (BFI) and CLL module of the MD Anderson Symptom Inventory (MDASI). Researchers also evaluated symptom-associated interference in daily activities.
Improvement in mean BFI score after 3 months and reduction of at least two points in a patient rating of their worst fatigue in the past 24 hours, as measured by BFI score, served as the study’s primary outcomes. Improvement in MDASI score and disease response assessment were secondary endpoints.
The median follow-up from enrollment was 11.3 months (interquartile range [IQR], 2-18) and the median duration of therapy with ruxolitinib was 7.7 months (IQR, 2-18).
At 3 months after the start of treatment, the mean percentage change from baseline was 44.3% (standard deviation [SD], 35; P < .0001) for the BFI score, 43.4% (SD, 51.5; P < .0001) for the symptom interference score and 42.1% (SD, 37.4; P < .0001) for the MDASI score.
“The significant improvement in symptoms assessed concomitantly by these three scoring systems indicated that excessive activation of JAK1/2 might induce disease-related symptoms,” Jain said.
Thirty-two patients (78%) experienced a 20% or greater reduction in the mean BFI, and 24 patients (59%) had a reduction of two points or more in worst fatigue score in past 24 hours.
Twenty-one patients discontinued ruxolitinib use. The most common reasons for discontinuation were disease progression and lack of response to treatment (n = 5 for each). Generally, ruxolitinib was not associated with the occurrence of any grade 3 or grade 4 adverse events, with three patients discontinuing treatment due to side effects. The most common grade 3 and grade 4 events were neutropenia (5%), hypertension (5%), insomnia (2%), tinnitus and dizziness (2%), and thrombocytopenia (2%).
“Overall, we have identified that ruxolitinib should be tested further as an agent for symptom control in CLL and in other cancers,” Jain said. “Ruxolitinib may also be tested as a therapeutic agent in CLL.”
This safety profile appeared different from a study by Spaner and colleagues and indicates further studies are needed, Stefano Molica, MD, from the Azienda Ospedaliera Pugliese-Ciaccio in Italy, and Emili Montserrat, MD, from the Institute of Hematology and Oncology, Hospital Clinic University of Barcelona in Spain, wrote in an editorial.
“That trial was interrupted because of a high incidence of anemia and no treatment effect on blood lymphocytosis, perhaps reflecting differences in disease status between patient populations,” Molica and Montserrat wrote. “The clinic-biological activity of ruxolitinib in CLL should be explored in other studies.”
A phase 1/phase 2 trial investigating the safety and efficacy of ibrutinib (Imbruvica; Janssen, Pharmacyclics) in patients with CLL and at high risk for progression will be launched soon, they added. – by Melinda Stevens
For more information:
Preetesh Jain, MBBS, MD, DM, PhD, can be reached at The University of Texas MD Anderson Cancer Center, Department of Leukemia, 1515 Holcombe Blvd. Unit 428, Houston, TX 77030; email: pjain@mdanderson.org.
Disclosure: Jain reports no relevant financial disclosures. One researcher reports a consultant role with and research support from Incyte. Molica and Montserrat report no relevant financial disclosures.