The International Chronic Lymphocytic Leukemia–International Prognostic Index (CLL-IPI) working group has developed an International Prognostic Index for patients with chronic lymphocytic leukemia based on a meta-analysis of individual patient data, as reported in The Lancet Oncology.
The meta-analysis included individual patient data from eight phase III trials performed in France, Germany, Poland, the United Kingdom, and the United States. Univariate and multivariate analyses were performed using 27 baseline factors and overall survival as an endpoint. A total of 3,472 treatment-naive patients were included in the full analysis data set, with 2,308 randomly segregated into the training dataset and 1,164 categorized into an internal-validation data set. Two additional data sets (n = 838 and 416) were used as external validation sets.
Five independent prognostic factors were identified in the training set: TP53 mutation status (no abnormalities vs del[17p] or TP53 mutation or both); IGVH mutation status (mutated vs unmutated), serum β2-microglobulin concentration (≤ 3.5 mg/L vs > 3.5 mg/L), clinical stage (Binet A or Rai 0 vs Binet B-C or Rai I-IV), and age (≤ 65 years vs > 65 years).
A weighted grading of the independent factors was developed, with TP53 mutation = 4, unmutated IGVH = 2, β2-microglobulin > 3.5 mg/L = 2, Rai I-VI or Binet B-C = 1, and age > 65 years = 1. The risk score ranged from 0 to 10, with 0–1 = low (28% of patients in training set), 2–3 = intermediate (39%), 4–6 = high (28%), and 7–10 = very high (5%). Overall survival at 5 years was 93.2% (95% confidence interval [CI] = 90.5%–96.0%) for low risk, 79.3% (95% CI = 75.5%–83.2%) for intermediate risk, 63.3% (95% CI = 57.9%–68.8%) for high risk, and 23.3% (95% CI = 12.5%–34.1%) for very high risk (P < .0001 overall; C-statistic = 0.723, 95% CI = 0.684–0.752).
The prognostic ability of these risk groups was confirmed in internal-validation and external-validation data sets.
The investigators concluded:
The CLL-IPI combines genetic, biochemical, and clinical parameters into a prognostic model, discriminating four prognostic subgroups. The CLL-IPI will allow a more targeted management of patients with chronic lymphocytic leukaemia in clinical practice and in trials testing novel drugs.