Health-Related Quality of Life Outcomes in Newly Diagnosed Chronic Myeloid Leukemia Patients Treated with Dasatinib and Low Dose Pegylated Interferon

Background: Tyrosine kinase inhibitors (TKI) have revolutionized CML treatment but only a minority of patients are candidates to discontinue their TKI treatment, i.e. achieve treatment-free remission (TFR). Therefore, for the majority of patients TKI treatments are lifelong and it becomes critical to understand impact of therapy on patients' health-related quality of life (HRQoL).To obtain a maximal response for TFR, second generation TKIs like Dasatinib (DAS) induce deeper and faster responses than imatinib,and combination with pegylated forms of interferon-α2 have shown promising effect in several studies.

Aims: To prospectively examine HRQoL outcomes in CML patients treated with DAS plus low-dose pegylated interferon- α2b (PegIFN).

Methods: We have performed a single armed study (NordCML007) using DAS 100 mg OD from inclusion through the study including 40 patients, of these 31 were male. From month 3 (M3) low-dose PegIFN was added for one year until M15. We chose, based on previous experience, a dose of only 15 µg/week for 3 months and if tolerated, the dose was increased to 25 µg/week from M6. At M12, 80% of patients still took PegIFN and the mean administered dose was 18 µg/week. Side effects were moderate and fewer patients than expected developed pleural effusions in the combination period. Efficacy of the combination measured by BCR-ABL1 RQ-PCR was superior to the historical control DASISION, exemplified by M12 achievement of MMR, 46% vs 86% and MR4, 12% vs 46%.

Before starting this project, concern was raised regarding tolerability of PegIFN. An acceptable tolerability of combined TKI+PegIFN is key for inclusion of combination treatment as standard of caretreatment. We did expect moderate negative effect of PegIFN treatment on HRQoL parameters. We assessed HRQoL with the well validated and widely used EORTC-QLQC30 questionnaire combined with the disease-specific CML module EORTC-CML24 at study inclusion and thereafter at 3, 6, 12 and at 18 months. Patient scoring was also compared with sex- and age-matched normative data.

Results: Patients completed HRQOL questionnaires at baseline, M3 (DAS only), M6 and M12 (on combination) and finally at M18 (DAS only). About 80% of HRQOL forms were completed, withh 31-33 respondents at each time point. Most of these patients completed all forms. CML patients at baseline had statistically and clinically significant poorer scores for "Overall quality of life" (65 vs 77 points), "Role functioning" (72 vs 87 points), "Emotional functioning" (73 vs 82 points,) "Social functioning" (79 vs 91 points), "Fatigue" (32 vs 19 points) and "Insomnia" (25 vs 16 points) compared to matched normal populations (a difference of >5 pts is estimated to representa difference of clinically significance) During treatment, scoring of all modalities approached the normative (i.e. no statistical difference), except for "Fatigue". Most of the improvement occurred during the first 3 months, i.e on DAS alone. Of note, HRQOL scores remained stable or improved further also with combination treatment, hence we observed no negative effect of low dose PegIFN treatment.

Conclusions: These preliminary results suggest that low-dose PegIFN in combination with DAS has no detrimental effects on HRQOL over time. Rather we observed improvement with regard to CML disease specific HRQOL domains. The efficacy, safety and HRQoL data encourages further study of PegIFN in combination with 2^nd generation TKIs.