External validation on a prospective basis of a nomogram for predicting the time to first treatment in patients with chronic lymphocytic leukemia

Background: A nomogram that incorporates traditional and newer prognostic factors to identify patients with chronic lymphocytic leukemia (CLL) who are at high risk of receiving therapy was developed by investigators at The University of Texas M. D. Anderson Cancer Center (MDACC). Because the model required validation before its extensive use could be recommended, the authors sought to externally validate the nomogram in an independent, community-based cohort of patients with CLL. METHODS: In total, 328 previously untreated patients with newly diagnosed, asymptomatic, Binet stage A CLL from different primary hematology centers who were registered on a prospective basis during 2006 to 2010 on an observational database of the Italian Lymphoma Study Group were considered suitable for external validation of the model. RESULTS: A total point score was calculated for each patient using a formula proposed by MDACC investigators, and the median score was 19.9 (range, 0-69.5). Furthermore, when the score was evaluated as continuous variable (ie, by measuring the risk of each point increase), the total point score was associated with the time to first treatment (hazard ratio [HR], 1.04; 95% confidence interval [CI], 1.02-1.05; P <.0001). Receiver operating characteristic analysis identified a point score of 25 (area under curve; 0.64; sensitivity, 61.5; specificity, 72.1; P <.0001) as the best threshold capable of separating patients who needed therapy from patients who did not (HR, 3.27; 95% CI, 2,07-5.18; P <.0001). The prognostic index category also remained a predictor of the time to first treatment when the analysis was limited to patients with Rai stage 0 disease (HR, 4.05; 95% CI, 2.25-7.52; P <.0001). Finally, a goodness-of-fit test demonstrated that the nomogram model had a significantly good fit at 2 years (correlation coefficient [r2] = 0.966; P =.002). CONCLUSIONS: The current results confirmed the ability of a newly developed prognostic index to predict the time to first treatment among previously untreated patients with CLL who had early disease and extended the utility of the model to those with Rai stage 0 disease. In addition, the actual and predicted time to first treatment outcomes revealed good agreement, suggesting that, externally, the results provided by the model are well calibrated.