Abstract

Background:Tyrosine kinase inhibitors (TKIs) have prolonged the survival of patients with chronic myeloid leukemia (CML). Nowadays, the life expectancy of these patients is approaching that of an age‐matched population. Since Imatinib, a first generation TKI, was first introduced 20 years ago, several newer more potent TKIs, have been approved for CML treatment. While these drugs are effective in treating CML, they come with the trade‐off of adverse effects. Some are common to all and some are drug‐specific. As most patients will receive lifelong treatment, quality of life (QOL) is becoming a major concern. Yet, QOL under treatment with these drugs has not been directly compared. In this study, we assessed the QOL and symptom burden in a cohort of patients with CML, using a patient reported outcomes (PROs) questionnaire.Aims:To compare QOL and symptom burden in patients with chronic phase (CP) CML treated with first generation compared to the newer generation TKIs.Methods:This is a nationwide study of patients with CP‐CML who were treated with TKIs. This study was initiated in collaboration with the Israeli CML Patients Organization. Study participants completed the validated European Organization for Research and Treatment of Cacner (EORTC) 30 items questionnaire (core30)and a supplementary EORTC 24 items CML‐specific questionnaire. Additional QOL items were added by the researchers and in addition demographics and treatment related information were documented. validated scales were used for evaluation. T‐test was used to compare the scales. We used the Mann‐Whitney test to compare medians and χ2 to compare categorical variables.Results:Overall, 129 patients completed the questionnaire. The median age of these patients was 56 (range: 25 to 89) years and 67 (60%) were males. Patients were treated with first generation TKIs [original imatinib (Gleevec®) (n = 21, 16%) or imatinib‐Teva (n = 25, 19%)] and second or third generation TKIs [dasatinib (n = 22, 17%), nilotinib (n = 17, 13%), bosutinib (n = 2, 1.5%) or ponatinib (n = 2, 1.5%)]. 22 patients (17%) discontinued TKI treatment. The median duration of treatment free remission (TFR) in patients who discontinued TKIs was 13 (range: 1 ‐ 59) months.The median age of patients who received first generation TKI was 67 (range: 32 ‐ 89) years, and 45 years (range: 25 ‐ 82) of patients treated with second or third generation TKIs (P < 0.0001). Patients on first generation TKIs expressed significantly more satisfaction from their quality of life during the preceding week (P = 0.006) and during the preceding 3 months (P = 0.001). Patients on first generation TKIs also reported lesser limitations in daily (P = 0.02) and social (P = 0.02) activities in the preceding week and also expressed a lesser degree of negative emotions such as anxiety or depression (P = 0.006). In patients treated with first generation TKIs the symptoms’ burden was significantly lower. For example, patients reported of less fatigue (P = 0.0021), less pain (P = 0.004), less dyspnea (P = 0.029) or constipation (P = 0.038), lesser degree of impaired body image (P = 0.01) and even less financial burden (P = 0.005) during the preceding week if they were treated with first generation TKIs. In a linear regression model, only the type of drug (first generation vs. newer generations) predicted global QOL (P = 0.006) whereas age and gender did not.Summary/Conclusion:The reported QOL of patients with CP‐CML who receive first generation TKI is superior to that of patients receiving newer generation TKIs.

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