Fatigue in Chronic Myelogenous Leukemia Patients (pts) Treated with Tyrosine Kinase Inhibitors (TKI),

Despite the excellent outcome for most patients (pts) with chronic myelogenous leukemia (CML) treated with tyrosine kinase inhibitors (TKIs), many experience chronic adverse events that compromise their quality of life and require multiple drug interruptions and discontinuations. Fatigue is one of the most common chronic problems among pts with CML treated with TKIs.

To investigate the pt characteristics and outcome of pts with CML treated with TKIs that report higher levels of fatigue versus pts reporting lower levels of fatigue.

We conducted a prospective, questionnaire-based study of pts with CML who were treated at our institution between March 2010 and May 2011. Pts were eligible if they were 18 years of age or older, were able to speak and read English, and were diagnosed with chronic phase (CP), Philadelphia chromosome-positive CML, confirmed by pathological and cytogenetic analysis. Pts with a history or recent diagnosis of CML in accelerated or blastic phase and pts with an active diagnosis of psychosis or severe cognitive impairment were excluded. Subjects completed the 26-item MD Anderson Symptom Inventory for CML multiple times over 6 months, including at baseline, three months, and six months. Symptoms, including fatigue, were rated on a severity scale from 0–10 (with 10 being as bad as could be imagined). Descriptive statistics, Fisher Exact test, and Mann-Whitney U tests were used to analyze the data.

A total of 148 pts were included in the analysis. The mean fatigue score for the overall sample was 2.95 (sd [standard deviation]=2.619). The median age was 52 yrs (range (r)=21–81). 138 patients received their current TKI for a median of 43 months (r=0–125) at the time of the first assessment. 2/138(1%) pts were receiving their initial therapy for CML and 82/138(59%) were receiving a TKI after failure of prior therapies. Pts were divided into two groups by trajectory analysis including a low fatigue group (LFG) with a mean fatigue score of 1.34 (sd=0.213) and a high fatigue group (HFG) with a mean score of 4.59 (sd=0.446). Median age was 53 (r=25–81) and 52 (r=21–78) yrs for the LFG and HFG respectively (P=0.48). Gender (P=0.69), race (P=0.25), education (P=0.15), and employment status (P=0.06) were not significantly correlated with group membership. Marital status was significantly correlated with group membership (P=0.007). More unmarried pts were in the HFG than in the LFG, and more married or partnered patients were in the LFG than HFG. Pts in the HFG had significantly higher scores of many symptoms such as pain (P=0.00001), disturbed sleep (P=0.00001), shortness of breath (P=0.0001), sadness (0.00003), swelling (0.0004), muscle soreness (P=0.00001), and malaise (P=0.00001) than pts in the LFG, but not higher scores of other symptoms such as diarrhea (P=0.07) and skin rash (P=0.22). There was no significant correlation with fatigue group membership for pts receiving imatinib (35 pts in LFG, 32 in HFG), dasatinib (18 pts in LFG, 17 pts in HFG), bosutinib (3 pts in LFG,4 pts in HFG), or other treatments (5 pts in LFG, 8 pts in HFG), but there was a trend for LFG membership for pts receiving nilotinib (18,8). Imatinib dose (high >400 mg daily; low ≤400 mg daily) was not significantly correlated with fatigue group membership (P=0.10). Pts who had good response to therapy at the time of the assessment (defined by a complete cytogenetic response and major or complete molecular response during study period) had similar fatigue group membership compared to the pts without good response. 124 pts had documented follow up at 3 months and 120 pts at 6 months. Mean fatigue score for the entire sample was 2.95 (sd=2.619) at baseline, 2.79 (sd=2.526) at 3 month, and 2.53 (sd=2.286) at 6 month. LFG mean fatigue scores were 1.33, 1.32, and 1.27 respectively. HFG mean fatigue scores were significantly higher (all P<0.01) at 4.81, 4.57, and 4.07 respectively.

The HFG had higher severity levels of other symptoms of pain, sleep disturbance, shortness of breath, sadness, swelling, muscle soreness, and malaise. Neither disease status nor treatment with different TKIs correlated with fatigue group membership. Marital status was the only socio-demographic variable that was correlated with fatigue group membership. Further possible determinants of fatigue severity and longer follow up studies are needed in future analyses.

Williams:Novartis: Research Funding. Ault:Bristol-Myers Squibb: Speakers Bureau; Novartis: Speakers Bureau. Cortes:Pfiser: Consultancy, Research Funding; Ariad: Consultancy, Research Funding; Bristol-Myers Squibb: Consultancy, Research Funding; Novartis: Consultancy, Research Funding.