Pflug, Natali

7015 Background: Besides clinical staging, a number of biomarkers predicting OS in CLL have been identified. The multiplicity of markers, limited information on their independent value, and a lack of understanding of how to interpret discordant markers are major barriers to use in routine clinical practice. We developed an integrated prognostic index using the database of the German CLL Study Group (GCLLSG), which was subsequently validated in a cohort of untreated CLL patients (pts) from the Mayo Clinic. Methods: The analysis was based on a dataset collected between 1997 and 2006 in 3 GCLLSG phase III trials. The external validation was performed on a series of newly diagnosed CLL pts managed at Mayo Clinic. Results: The GCLLSG dataset (1,948 physically fit pts at early and advanced stage; median age: 60 yr (range 30-81); median observation time 63.4 mo) was used as a training dataset. 7 parameters were identified as independent predictors for OS: sex, age, ECOG status, del 17p, del 11q, IGHV mutation status, thymidine kinase and β2-microglobulin. By using a weighted grading a prognostic index was derived separating four different pts groups: low risk (score 0 - 2), intermediate risk (score 3-5), high risk (score 6-10) and very high risk (score 11-14) with significant different OS rates (95.2%, 86.9%, 67.7% and 18.7% OS after 5 yr for the low, intermediate, high and very high risk group respectively (p<0.001). This prognostic index was validated in a cohort of 676 newly diagnosed, untreated pts from the Mayo Clinic (median age 61.5 yr (range 32 - 89); median observation time 47.0 mo). The 4 risk groups were reproduced with 98.3%, 95.4%, 75.4% and 10.8% OS after 5 yr. The prognostic index predicts OS independent of Rai/Binet stage and provides accurate estimations regarding time to first treatment (TTF). C-statistic is 0.75. Conclusions: Using a multi-step process including external validation, we developed a comprehensive prognostic index combining clinical, serum, and molecular information into a single risk score for pts with untreated CLL. The prognostic index provides more accurate prediction of both TTF and OS. To our knowledge it is the first prognostic model in CLL to reach the C-statistic threshold (c > 0.70) necessary to have utility at the level of the individual.

Key PointsPrognostic tool for CLL patients with high discriminatory power compared with conventional clinical staging systems. Prognostication on the individual patient level independent of clinical stage.