The Total Amount of Kappa Plus Lambda Serum Immunoglobulin Free Light Chains (sFLC κ+λ) Is a Powerful Independent Predictor of Time to First Treatment In Chronic Lymphocytic Leukemia (CLL) and Allows Definition of a Novel Prognostic Scoring System: A Study of 449 Therapy-naïve Patients

Abstract 2437 Clinical course in individual CLL patients (pts) is highly heterogeneous. Several pts show an indolent disease and other experience an aggressive course rapidly succumbing to disease-related events. Different biomarkers have been developed to identify pts with evolving disease but their application is mostly limited to clinical trials. It has been shown that measurement of clonal serum free light chains (sFLC) levels, through a straightforward assay validated for plasma cell disorders, could independently identify CLL pts with progressive disease. By analyzing the largest cohort of CLL pts ever reported, we wished to: i) determine the independent predictive value of sFLC abnormalities in the context of established biomarkers; ii) define the predictive hierarchy of these markers; iii) incorporate sFLC into a novel prognostic system. Cryopreserved sera at diagnosis from 449 untreated pts (282 males and 167 females, median age 65 yrs; r 33–89) were collected for analysis at two reference laboratories. After quantization (Freelite, The Binding Site, Ltd., UK) of sFLC k and l levels (r, k: 3.3–19.4 mg/mL; l: 5.71–26.3 mg/mL), their ratio was calculated as sFLC k/l (r: 0.26–1.65). An abnormal sFLCk/l was found in 150/449 cases (132 k/18 l). A significant correlation emerged between sFLCk/l and CD38, ZAP70, unmutated IgHV and unfavourable FISH but not with Binet stage (Table). At a median follow up of 3 yrs (r 1–20), 149 of 449 pts were treated due to progressive disease (NCI Guidelines). Treatment-free survival (TFS) was significantly shorter (p60.6 mg/mL (HR=2.5, C.I. 2.6–3.9), remained the strongest independent predictor of TFS together with ZAP70 (HR=2.8, C.I. 1.8–4.6) and stage (HR=2.5, C.I. 1.6–3.8), while CD38 and IgVH status lost their predictive power. Most intriguingly, it emerged that sFLCk/l is irrelevant in predicting TFS if sFLCk+l is above cut-off and that cytogenetic risk remains significantly associated with sFLCk+l (P=0.047) but not FLCk/l. sFLCk+l retained an independent association with TFS together with cytogenetics, ZAP70 and stage. A novel prognostic model was then constructed with 1 point for each of these unfavorable marker and a score given by their sum. On 260 pts scores were: 104=0, 79=1, 56=2, 19=3, 4=4. The 3 year probability of avoiding treatment was 94.8%, 84.5%, 61.6% and 21.1% for pts scoring 0, 1, 2 and 3+4, respectively (P sFLC k/l in 449 untreated CLL pts Table 1. Death in complete remission by year sFLC k/l P Normal (%) Abnormal (%) CD38 − 234 (70.9) 96 (29.1) Disclosures: Amoroso: The Binding Site, LtD: Consultancy.