Quality of Life (QoL) and Clinical Outcomes of Dasatinib Treatment in TKI-Naive and Early Switched from Imatinib Patients with Chronic Myeloid Leukemia in Chronic Phase (CP CML) in a Real World Setting
Authors: Ionova Tatyana , Bulieva Natalia , Vinogradova Olga , Kurbatova Kira , Lomaia Elza , Nikitina Tatyana , Novitskaya Natalia , Rodionova Anna , Usacheva Elena , Chukavina Marina , Shumkova Marina 
Published: October 2019

Abstract
Dasatinib as a front-line is a promising treatment option for CP-CML pts. Assessment of benefits and risks of this treatment regimen both from physician's and patient's perspective sounds worthy. We aimed to study QoL and clinical outcomes of dasatinib as a front-line treatment in CP CML pts in a real world setting.
The total of 30 pts with CP CML (16 pts - TKI-naive, 14 pts - early switched to dasatinib after failure of imatinib treatment, median duration of imatinib treatment - 6 mths; switched pts) were involved in the multicenter observational prospective study. Median age - 47.6 y.o. (20-74), female - 33.3%; median disease duration - 5 mths; distribution of pts according to the Sokal score - 27.6% pts at low risk, 41.4% - at intermediate risk, 31% - at high risk. 27% pts had comorbidities: median Charlson Comorbidity Index was 3.0. All the pts filled out the QoL questionnaire SF-36 before dasatinib treatment, 3 and 12 mths after treatment start. Hematological, cytogenetic and molecular response rates (HR, CyR, MR) were registered after 3 and 12 mths of dasatinib treatment. Healthy controls (n=30) from QoL population normative database adjusted by age and gender to pts group were used for QoL comparison at baseline. Group comparisons were made using Mann-Whitney test, ANOVA and Wilcoxon matched pair test.
QoL in CP CML pts at baseline was lower than in healthy controls: Integral QoL Index - 0.358 in pts vs 0.497 in healthy controls (p<0.05). Physical functioning in CP CML pts was significantly lower than in healthy controls: 78.8 vs 90.8 (p<0.05). No QoL differences were found between TKI-naive and switched pts before dasatinib treatment (p>0.05). During 12 months of dasatinib treatment positive changes in QoL were observed: Integral Quality of Life Index increased from 0.358 at baseline to 0.493 after 12 mths (p=0.05) and became comparable to healthy controls (p>0.05). Significant QoL improvement was registered in 12 mths of dasatinib treatment for role emotional (48.1 vs 81.5), role physical (44.4 vs 56.5) and social functioning(62.5 vs 80.6); p<0.05. Clinical outcomes were similar to the data of randomized clinical trials. After 3 mths of dasatinib treatment the majority of pts (92%) achieved complete HR, others had partial HR. After 12 mths of treatment 81.6% pts maintained or achieved complete HR; 69.2% pts exhibited complete CyR; 53.8% pts - major/complete MR. Four pts were dropped out of the study due to resistance to dasatinib (n=2) or due to severe AE (n=2). No cases of death were observed during the study. AE were similar to the ones registered within the clinical trials: in the most cases they were non-severe/moderate; severe AE (lung edema, bleeding from stomach ulcer) were observed in 2 pts; no cases of pleural effusion were revealed.
In conclusion, patient-reported and clinical outcomes of dasatinib treatment in TKI-naïve pts and in pts early switched to dasatinib after failure of imatinib were obtained in a real world study. Significant QoL improvement in terms of role physical, role emotional and social functioning was observed. Clinical outcomes support the data obtained in clinical trials. Benefits and risks of front-line treatment with dasatinib in CML-CP both from physician's and patient's perspective were demonstrated in a real world setting.

Disclosures
Ionova: BMS: Research Funding; MSD: Speakers Bureau. Bulieva:BMS: Research Funding. Vinogradova:BMS: Research Funding. Kurbatova:BMS: Research Funding. Nikitina:BMS: Research Funding. Novitskaya:BMS: Research Funding. Rodionova:BMS: Research Funding. Usacheva:BMS: Research Funding. Chukavina:BMS: Research Funding. Shumkova:BMS: Research Funding.