DP070 | FREE LIGHT CHAIN RATIO IS AN INDEPENDENT RISK FACTOR FOR PROGRESSION TO SYMPTOMATIC WALDENSTROM MACROGLOBULINEMIA

Background. Free Light Chains (FLC) prognostic role in Waldenstrom’s Macroglobulinemia (WM) or IgM monoclonal gammopathies has been not well investigated. Aim. We sought to evaluate whether an abnormal FLC ratio confers a higher risk of progression to symptomatic WM in patients with IgM-MGUS, IgM-related disorders or asymptomatic WM. Methods. We reviewed data from two prospectively maintained databases including 613 patients, diagnosed and followed at Division of Hematology of IRCCS Policlinico San Matteo and Azienda Ospedale-Università Padova between 2000 and 2023. Patients were classified as IgM-MGUS, IgM-related disorders, asymptomatic or symptomatic WM according to the diagnostic criteria established at the second International Workshop on WM (Owen et al 2003). Statistical analysis. FLC effect on progression was evaluated by multivariable Fine&Gray regression model for competing events. Parameters with a p-value<0.15 at univariable analysis entered multivariable models. Two sided type I error was set at 5%. Results. Baseline serum FLC were available in 402 patients: 176 (43.8%) with IgM-MGUS or IgM-related disorder, 137 (34.1%) asymptomatic WM and 89 (22.1%) symptomatic WM. An abnormal FLC ratio was detected in 58/176 (33%) patients with IgM-MGUS/IgM-related disorder, 100/137 (73%) patients with asymptomatic WM and 69/89 (77.5%) patients with symptomatic WM. The median period of follow-up was 6.5 years. The 5-year cumulative incidence of progression was higher in patients with an abnormal FLC ratio, both in IgM-MGUS/IgM-related disorders (8.7%, 95%CI: 3.2-17.8% vs 2.6% 95%CI: 0.7-6.8%, Pepe&Mori test p=0.023) and in asymptomatic WM (35.4%, 95%CI: 25.1-45.8% vs 8.3% 95%CI: 2.1-20.1%, Pepe&Mori test p=0.011). At univariable analysis, a higher risk of progression was found in patients with an abnormal FLC ratio (sub-hazard ratio, sHR=4.5, 95%CI: 2.6-8.0, p<0.001), in those with asymptomatic WM (vs other IgM related disorders), in patients with polyclonal IgG <800 mg/dL, with lactate dehydrogenase LDH < 225 mU/ml, with hemoglobin <12 g/dL and with serum albumin <3.5 g/dl. After adjusting for diagnosis, reduction of polyclonal IgG, lactate dehydrogenase LDH, hemoglobin and serum albumin, abnormal FLC ratio maintained its prognostic impact on progression (sHR=2.53, 95%CI: 2.0-3.2, p<0.001). Conclusions. In this study we demonstrated that an abnormal FLC ratio is an independent risk factor for progression to symptomatic WM.