VALIDATION OF THE EUTOS SCORE FOR PREDICTION OF COMPLETE CYTOGENETIC RESPONSE AND PROGRESSION FREE SURVIVAL: APPLICATION TO INDEPENDENT DATA FROM THE EUTOS REGISTRY AND REVIEW OF PUBLICATIONS

Background:

The EUTOS score is predictive for complete cytogenetic remission (CCyR) at 18 months and subsequent progression free survival (PFS) in patients with chronic phase Chronic Myeloid Leukemia (CML) treated first line with imatinib. The score uses percentage of basophils and spleen size to classify patients into a high and a low risk group (Hasford et al., Blood 2011).

Aims:

The EUTOS score was developed and independently validated on patients enrolled in prospective, protocol-based phase III- and IV- studies of frontline therapy which typically recruit highly selected patients only. Now the score is tested in routine CML-patients, registered prospectively by National Study Groups and who were not included in clinical trials. Additionally, publications on validity of the EUTOS score are reviewed.

Methods:

A total of 1288 patients were collected from a hospital-based national group located in Madrid (n=193), from the national Polish registry (n=281), from two Russian registries located in Moscow and in St. Petersburg (n=493), from two Czech registries (Camelia and Infinity) (n=309, including 96 patients from Slovakia), and from a Romanian registry (n=12). PFS, time to CCyR and CCyR status 18 months after the start of therapy were calculated and analyzed using Kaplan-Meier and cumulative incidence curves, and respective Gray and Log-Rank tests. For cumulative incidence analyses death was considered a competing risk. PFS was measured from the start of imatinib treatment to date of death or progression to blastic or accelerated phase. PubMed and Abstract Books of relevant conferences were searched for publications on the EUTOS score. Information on sample size, percentage of high risk patients, median age and follow up time was collected.

Results:

Of 1288 patients 52% were male. Median age was 49 years (range 18-85), and median observation time was 65 months (range 2-112). There were 161 (12.5%) high risk patients. At 18 months 61.3% of the patients in the high risk and 73.0% of the low risk group were in CCyR (P=.036). In high risk patients, the cumulative probability of ever achieving a CCyR over the whole observation time, was significantly lower than in low risk patients (P<.0001), being 67.6% (95% CI 59.1–74.7) vs. 84.4% (95% CI82.1% - 86.7%) at 5 years. This indicates that patients not treated in clinical studies achieve CCyR later than patients enrolled in clinical trials. PFS differs significantly for EUTOS high and low risk group (P=.0395). After 5 years PFS was 89.3% (95% CI 87.1% - 91.1%) in low risk patients vs. 82.0% (95% CI 74.7% - 87.3%) in the high risk ones. Thus even in this sample of non-trial patients the EUTOS score identified two distinct prognostic groups. There were eight publications on the validity of the EUTOS score identified. Authors were located in Europe, Asia, North and South America and their reports included 139 to 279 patients. Median age ranged from 43 to 55 years, and median follow up time ranged from 29 to 117 months. Percentage of patients in the EUTOS high risk group started at 5% in Italy and went up to 31% in Singapore (median 9.6%). Most publications discussed patients treated with imatinib, a study from the USA had 34% of patients treated with second-generation tyrosine kinase inhibitors (TKIs) a study from Italy reported exclusively on patients with second-generation treatment. Further, six studies reported P-values for the cumulative incidence of CCyR, most of them indicating major differences between high and low risk group and half of them below 0.05. Six studies specified P-values for PFS, ranging from 0.01 to 0.73, four studies reported P-values of 0.05 or lower.

Summary and Conclusions:

The validity of the EUTOS score was confirmed in the patients treated outside of prospective, protocol-based clinical studies. In addition, many independent studies from all over the world reported a substantial predictive value for cytogenetic remission and progression free survival. Even considering the comparatively small number of events in patients treated with TKIs the combined evidence indicates that the EUTOS score is able to reliably identify a small group of patients at high risk of suboptimal outcome.

Abstrakta v časopise Haematologica 2013, Suppl1

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