ANALYSIS OF TREATMENT AND OUTCOME DATA OF 2904 PATIENTS FROM THE EUTOS POPULATION-BASED REGISTRY

Background
Most of the knowledge about treatments and outcomes of patients with chronic myeloid leukemia (CML) originates from clinical trials. To get new and unbiased insights the European Treatment and Outcome Study (EUTOS) for CML collected population based data in 20 European countries.

Aims
The population-based registry was set up inside the infrastructure of the EUTOS to further explore the epidemiology, patient and disease characteristics, treatment and outcomes of CML in Europe. This work focuses on the treatment and early outcomes of CML in Europe.

Methods
The population-based registry aimed to identify and to document all newly diagnosed adult patients with Ph+ and/or BCR-ABL+ CML at any stage of disease in whole countries or specified regions in Europe. First-line treatment and treatment changes were documented.  Cytogenetic responses are analyzed using cumulative incidences considering death and progression as competing risks.

Results
Overall 2904 Ph+ and/or BCR/ABL1+ adult CML-patients were registered. 94% of the patients were diagnosed in chronic phase (CP), 3.5% in accelerated phase (AP) and 2% in blastic phase (BP). 57% of patients were male. The median age was 56 years (18-99). Clonal chromosomal abnormalities (CCAs) in Ph+ cells were found in 11% of patients. 12% of the patients were at high risk of not achieving CCyR 18 months after start of therapy according to the EUTOS score. According to the Euro score 38% of patients were low risk, 51% intermediate risk and 11% high risk.

The follow-up data of 2499 and the first-line therapy of 1986 patients were documented, for 1954 patients both, first-line therapy and follow-up is known.

As first-line therapy 81% of patients received imatinib, 12% nilotinib, 3% dasatinib and 4% a treatment based on HU. Patients with high EUTOS or Euro risk and patients in AP and BP did not receive second generation tyrosine kinase inhibitors (TKIs) as a frontline therapy more often than patients with low EUTOS risk or Euro low and intermediate risk or in chronic phase (16% EUTOS low risk vs. 13% EUTOS high risk, 16% euro low risk vs. 14% Euro high or intermediate risk, 16% in CP vs. 12% in AC or BP received second generation TKIs). Patients with CCAs in Ph+ cells, however, received more often second generation TKIs (22% vs. 15%).

Median time to first complete cytogenetic remission (CCyR) was 8 months for all patients. There were major differences observed between different EUTOS classes (high: 13 months vs. low: 8 months), CCAs in Ph+ cells (with CCAs: 10 months vs. without CCAs: 8 months) and treated with different medications first-line (Imatinib: 8 months vs. second generation TKIs: 5 months).

Survival probabilities 12 and 24 months after diagnosis were 95% and 92%, respectively. Stratified by Euro score the survival probability at 12 months was 97% for Euro low and intermediate risk patients and 96% for Euro high risk patients. At 24 months the survival probability was 96%, 93% and 91%, for Euro low, intermediate and high risk, respectively.

Summary
This is the first analysis of the treatment and outcome data from the EUTOS population-based registry, which provides an unselected sample of Ph+ and / or BCR/ABL1+ adult CML patients in Europe. Imatinib is the first choice in treatment of CML, while second generation TKIs as a first-line treatment are not very common. Median time to CCyR in the population is comparable to the one reported in patients enrolled in prospective randomized trials, while survival at 12 and 24 months are lower probably due to the selection of patients that are included in clinical trials.'

Keyword(s): Chronic myeloid leukemia, Outcome, Tyrosine kinase inhibitor

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