Validation of the CLL-IPI and comparison with the MDACC prognostic index in newly diagnosed patients

Recently, an international collaboration collected information from ∼3500 chronic lymphocytic leukemia (CLL) patients to develop a comprehensive tool for predicting overall survival (OS) (the international prognostic index for patients with chronic lymphocytic leukemia [CLL-IPI]).1 This score built on TP53 deletion and/or mutation, IGHV mutational status, β2-microglobulin (β2-M), clinical stage, and age may represent a simple “globally applied” model applicable in daily clinical practice and able to improve risk stratification for all CLL patients. Although it was primarily developed to predict OS, this tool can also predict time-to-first treatment (TTFT) in newly diagnosed patients.2 \n \nHerein, we evaluated the validity and reproducibility of the CLL-IPI in an independent cohort of newly diagnosed and nonreferred CLL patients collected from 5 Italian centers. We also evaluated whether CLL-IPI could predict TTFT. Finally, we compared this tool with the score proposed by the MD Anderson Cancer Center (MDACC) group3 in both the Italian cohort and in an additional cohort of newly diagnosed CLL patients from the Mayo Clinic (Rochester, MN). The study was approved by Institutional Review Boards with informed consent in accordance with the Declaration of Helsinki. \n \nCLL databases from 5 Italian centers were established for research purposes (supplemental Appendix, supplemental Figure 1, available on the Blood Web site). A total of 858 newly diagnosed and previously untreated CLL patients were included in this analysis. The majority of patients were Binet stage A (79.7%); median age was 65.5 years (supplemental Table 2 lists baseline patient features). After a median follow-up of 5.8 years (range, 3 months to 27.5 years), 167 patients died and 304 were treated (130 patients received chemotherapy and 174 received chemo-immunotherapy). \n \nWe evaluated the relationship between CLL-IPI and OS. Due to missing data regarding TP53 mutations, del17p was used as the sole marker of TP53 status. All parameters showed an independent prognostic impact (supplemental Table 3). \n \nAccording to the CLL-IPI, 471 patients were classified as low risk, 214 as intermediate risk, 139 as high risk, and 34 as very high risk. Stratification of patients according to the CLL-IPI showed significant differences in terms of OS (Figure 1A). The median, 5-year, and 10-year OS rates by CLL-IPI category in our cohort are quite similar to those observed in the original study1 (supplemental Table 4), suggesting that the survival estimates provided by the index are reproducible. The C-statistic was 0.71 (P < .0001) for predicting OS, exceeding the 0.70 threshold and underscoring the prognostic utility at the individual patient level.