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This controlled comparison study evaluated objective and subjective cognitive function and their relationships with patient-reported symptoms (depression, fatigue, insomnia) in patients receiving tyrosine kinase inhibitors (TKIs) for chronic myeloid leukemia (CML) and non-cancer controls. Patients with CML in chronic phase treated with the same oral TKI for ≥6 months (n = 90) and non-cancer controls (n = 87) completed a neurocognitive battery and self-report measures. Patients demonstrated worse overall neuropsychological performance (p =.05) and verbal memory (p =.02) compared to controls. Patients were not more likely to meet criteria for impaired cognitive performance compared to controls (ps>.26). Patients reported worse subjective global and domain-specific cognitive complaints and less satisfaction with cognitive function compared to controls (ps <.05). Patients also reported greater fatigue and insomnia symptoms (ps <.001). In both groups, greater fatigue, insomnia, and depressive symptoms were associated with worse subjective cognition (ps <.01). Longitudinal studies are needed to examine changes in cognitive function in patients before and during TKI treatment. [ABSTRACT FROM AUTHOR]

Background: Cognitive behavioral therapy for targeted-therapy related fatigue (CBT-TTF) has demonstrated preliminary efficacy in reducing fatigue in patients treated with tyrosine kinase inhibitors (TKIs) for chronic myeloid leukemia (CML).Purpose: The aim of the current analyses was to explore whether fatigue perpetuating factors (disturbed sleep/wake cycle, dysregulated activity patterns, maladaptive cognitions about fatigue and cancer, insufficient processing of cancer and treatment, inadequate social support and interactions, heightened fear of cancer progression) changed over time in patients receiving CBT-TTF, and whether the effect of CBT-TTF on fatigue was mediated by these factors.Methods: Secondary data analyses were conducted from a pilot randomized controlled trial. Patients with CML treated with a TKI who reported moderate to severe fatigue were randomized 2:1 to CBT-TTF delivered via FaceTime for iPad or a waitlist control condition (WLC). Self-report measures of fatigue and fatigue perpetuating factors were obtained before randomization and post-intervention (i.e., approximately 18 weeks later). Mixed model and mediation analyses using bootstrap methods were used.Results: A total of 36 participants (CBT-TTF n = 22, WLC n = 14) who had baseline and 18-week follow-up data and attended >5 sessions for CBT-TTF were included. Participants randomized to CBT-TTF reported improvements in activity (mental, physical, social, p's ≤ .023) and cognitions (helplessness, catastrophizing, focusing on symptoms, self-efficacy, p's ≤ .003) compared to WLC. Mental activity, social activity, self-efficacy, helplessness, and focusing on symptoms, as well as sleep and insufficient processing (avoidance) mediated the relationship between treatment group and fatigue.Conclusions: CBT-TTF appears to improve TKI-related fatigue in CML patients through changes in behavior (sleep, activity patterns) and cognitions about fatigue and cancer. A larger randomized controlled trial is warranted to confirm these findings. [ABSTRACT FROM AUTHOR]

Background: Fatigue is a common and disabling side effect of targeted therapies such as tyrosine kinase inhibitors (TKIs) used to treat chronic myeloid leukemia (CML). The goal of the current study was to conduct a pilot randomized trial of the first cognitive behavioral intervention developed for fatigue due to targeted therapy.Methods: Patients with CML treated with a TKI who were reporting moderate to severe fatigue were recruited and randomized 2:1 to cognitive behavioral therapy for targeted therapy-related fatigue (CBT-TTF) delivered via FaceTime for the iPad or to a waitlist control (WLC) group. The outcomes were acceptability, feasibility, and preliminary efficacy for fatigue (Functional Assessment of Chronic Illness Therapy-Fatigue; primary outcome) and quality of life (Functional Assessment of Cancer Therapy-General; secondary outcome). Participants were assessed before randomization and after treatment (ie, approximately 18 weeks later).Results: A total of 44 patients (mean age, 55 years; 48% female) were assigned to CBT-TTF (n = 29) or WLC (n = 15). The study participation rate was 59%. Among the patients assigned to CBT-TTF, 79% completed the intervention. Intent-to-treat analyses indicated that patients assigned to CBT-TTF demonstrated greater improvements in fatigue (d = 1.06; P < .001) and overall quality of life (d = 1.15; P = .005) than those assigned to WLC. More patients randomized to CBT-TTF than WLC demonstrated clinically significant improvements in fatigue (85% vs 29%) and quality of life (88% vs 54%; P values ≤ .016).Conclusions: CBT-TTF displays preliminary efficacy in improving fatigue and quality of life among fatigued patients with CML treated with TKIs. The findings suggest that a larger randomized study is warranted. [ABSTRACT FROM AUTHOR]

Highlights • Inhibition of pSTAT3 may alter the bone marrow and sensitize CML stem cells to TKI. • Ruxolitinib and nilotinib can be safely combined in patients with chronic-phase CML. • Molecular responses after combination therapy are encouraging. Abstract Purpose Preclinical evidence indicates that the bone marrow microenvironment provides a protective niche for leukemic stem cells, allowing them to evade the effects of BCR-ABL tyrosine kinase inhibitors (TKIs), but that targeting of the JAK-STAT pathway with the JAK2 inhibitor ruxolitinib increases TKI-induced apoptosis. A phase I clinical trial (NCT01702064) investigated the tolerability and safety of treating chronic-phase chronic myeloid leukemia patients with ruxolitinib in combination with the BCR-ABL TKI nilotinib and explored initial efficacy evidence. Experimental design Eleven patients already treated with single-agent nilotinib (300–400 mg twice daily) commenced combination therapy, and molecular responses were evaluated after 6 months. Three ruxolitinib dose cohorts were studied: 5 mg, 10 mg, and 15 mg twice daily. Results One patient experienced a grade 3/4 adverse event (hypophosphatemia) and 36% of patients experienced grade 1/2 anemia. Of 10 patients who were evaluable for responses, 40% had undetectable BCR-ABL transcripts, as measured by quantitative RT-PCR after 6 months. Plasma inhibitory assay results revealed a decrease in phospho-STAT3 levels after treatment with ruxolitinib. The recommended phase 2 dose of ruxolitinib was 15 mg BID. Conclusions Overall, this combination was safe and well-tolerated, and the molecular responses were encouraging, thereby warranting further investigation in a phase 2 trial. [ABSTRACT FROM AUTHOR]