Abstract

Abstract 3838

Background:

Symptom burden is the combined impact of symptoms from disease and treatment on daily functioning. Lack of symptom recognition may result in failure to address symptoms and maximize patient functioning. Patient-reported outcomes (PROs) can be endpoints in clinical trials to establish treatment benefits. The purposes of this study are to develop a short, easily understood, valid, and reliable patient questionnaire for measuring Philadelphia-chromosome-positive chronic myeloid leukemia (CML) symptom burden and to describe the symptom burden. This abstract reports preliminary results.

Methods:

The 13 core symptom items and 6 interference items of the M. D. Anderson Symptom Inventory (MDASI), rated on a 0-to-10 scale, are the base for the MDASI-CML. In addition, 6 CML-specific symptom items were generated from interviews with patients and the ratings of an expert panel. 160 patients with CML will complete the MDASI-CML every 2 weeks for one year using interactive voice response (IVR) technology. Information on performance status and quality of life will be collected every 3 months. Psychometric analyses will reduce the number of items to the optimal set describing symptom burden; determine predictive, construct, and concurrent validity; and establish internal consistency and test-retest reliability. The feasibility of collecting symptom data from this population of chronic disease patients using IVR technology will be assessed. The symptom burden of CML will be described through descriptive, correlational, cluster, and factor analyses.

Results:

As of June 30, 2010, data was available on 71 patients. Average age at study enrollment is 51.6 years, 62% are male, 97.2% are in the chronic phase of CML, 91.5% are receiving kinase inhibitor (KI) therapy, and all patients have a clinician-rated ECOG performance status of 1 or less. Four patients have dropped out of the study because of time required to complete assessments. 70.5% (249/353) of IVR calls have been completed as planned, and 66% of patients have responded to at least 80% of planned calls. The reliability index (Cronbach alpha) for the 13 core symptom items is 0.90, for the 6 CML-specific items is 0.75, and for the 6 interference items is 0.93. Thirty-five patients on KI therapy reported symptoms for at least 3 months. An exploratory analysis of the area under the curve of the most severe symptoms and interference for the 3 groups over the initial 3 months of the study is shown in Table 1.

CORE SYMPTOMS TYPE OF KI THERAPY 
Imatinib N = 19 Dasatinib N = 8 Nilotinib N = 6 
Mean AUC SD Severity Rank Mean AUC SD Severity Rank Mean AUC SD Severity Rank 
Fatigue 252.4 174.3 243.9 239.7 127.1 130.7 
Drowsiness 216.2 174.3 133.6 83.7 104.3 160.2 
Disturbed sleep 188.4 176.0 232.1 339.7 94.2 110.3 
Difficulty remembering 160.1 134.9 143.4 209.3 105.3 140.5 
Distress 156.7 162.3 123.8 167.6 101.3 106.2 
Shortness of breath 127.3 133.6 136.3 195.7 99.8 143.6 
Pain 122.8 152.2 204.1 230.6 48.8 70.2 11 
CML-SPECIFIC SYMPTOMS 
Muscle soreness/cramping 243.9 193.9 217.1 248.8 80.6 99.9 
Swelling 221.2 178.9 191.6 286.4 58.4 76.7 
Malaise 140.2 146.0 147.2 202.5 77.3 105.1 
Rash 124.5 110.1 125.8 100.2 131.5 83.6 
INTEFERENCE ITEM 
Work 165.9 158.6 213.7 244.8 55.67 84.7 
Walking 143.2 160.2 293.3 257.2 42.7 64.8 
General Activity 167.0 157.9 183.2 221.4 50.8 67.7 
Mood 141.8 143.7 162.1 226.0 53.7 84.7 
CORE SYMPTOMS TYPE OF KI THERAPY 
Imatinib N = 19 Dasatinib N = 8 Nilotinib N = 6 
Mean AUC SD Severity Rank Mean AUC SD Severity Rank Mean AUC SD Severity Rank 
Fatigue 252.4 174.3 243.9 239.7 127.1 130.7 
Drowsiness 216.2 174.3 133.6 83.7 104.3 160.2 
Disturbed sleep 188.4 176.0 232.1 339.7 94.2 110.3 
Difficulty remembering 160.1 134.9 143.4 209.3 105.3 140.5 
Distress 156.7 162.3 123.8 167.6 101.3 106.2 
Shortness of breath 127.3 133.6 136.3 195.7 99.8 143.6 
Pain 122.8 152.2 204.1 230.6 48.8 70.2 11 
CML-SPECIFIC SYMPTOMS 
Muscle soreness/cramping 243.9 193.9 217.1 248.8 80.6 99.9 
Swelling 221.2 178.9 191.6 286.4 58.4 76.7 
Malaise 140.2 146.0 147.2 202.5 77.3 105.1 
Rash 124.5 110.1 125.8 100.2 131.5 83.6 
INTEFERENCE ITEM 
Work 165.9 158.6 213.7 244.8 55.67 84.7 
Walking 143.2 160.2 293.3 257.2 42.7 64.8 
General Activity 167.0 157.9 183.2 221.4 50.8 67.7 
Mood 141.8 143.7 162.1 226.0 53.7 84.7 

Fatigue was the most severe symptom reported by patients regardless of type of KI therapy. While the sample size is too small to determine significant differences, there is a trend toward lower symptom burden in nilotinib patients. Large effect sizes (>0.5) were found between mean AUCs for fatigue, disturbed sleep, pain, muscle soreness and cramping, and swelling in nilotinib patients and both imatinib and dasatinib patients. In addition, there were large effect sizes between mean interference AUCs for work, walking, general activity, and mood in nilotinib patients and both imatinib and dasatinib patients. Implications: Collecting symptom assessments at regular intervals using an IVR system is feasible and useful in patients with CML receiving KI therapy, as patients may experience significant symptom burden, especially fatigue. Different KI drugs may influence the level of symptom burden. The results of this preliminary analysis warrant further investigation of the symptom burden of KI therapies. Data collection for this study is ongoing.

Disclosures:

No relevant conflicts of interest to declare.

Author notes

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Asterisk with author names denotes non-ASH members.