A role of light as potential biomarker for progression of smoldering to symptomatic multiple myeloma

Background:In 2014 the definition of smoldering multiple myeloma (sMM)was updated by the International Myeloma Working Group (IMWG). Thus,at present, the detection of SLIM CRAB can be considered for treatmentneed. In addition, several clinical and biological predictors of progressionto symptomatic MM can be used to discriminate sMM patients on the basisof their different degree of risk of progression. Beside to the validated criteriaincluded in Mayo Clinic or Spanish models, several other potential bio-markers have been each time proposed. We previously demonstrated thatLIGHT/TNFSF14, a TNF superfamily member, is over-expressed on CD14+monocytes, CD8+ T-cells and neutrophils of patients with MM lytic bonedisease.Aims:Given lytic bone disease as the most frequent MM-defining event insymptomatic MM patients, here we aimed to test LIGHT as potential bio-marker for progression of sMM to symptomatic MM.Methods:PB samples were obtained from 58 patients (30 M/28 F, 63±10years) newly diagnosed as having symptomatic MM with related-bone dis-ease, 60 with sMM (36/24, M/F, 54±20 years) and 50 healthy controls.Patients and controls were age and sex matched. Patients were diagnosedas having symptomatic MM or sMM based on IMWG criteria. By meansof multiparameter flow cytometry (MFC), we evaluated LIGHT expressionon circulating CD14+-monocytes, CD16+-neutrophils, CD4+- and CD8+-T cells. The results were compared to those obtained in healthy controls.Results:The levels of LIGHT measured on CD14+ monocytes of sympto-matic MM, sMM patients, compared to those of healthy controls gave thefollowing results: 47.1%±9.5% (range 30-90%), 14.75%±20% (range0-88%)vs 2.1%±1.2 (range 0-4%), p<0.01. In addition, we found that insMM patients, LIGHT levels positively correlated with high involved/unin-volved serum free light chain (FLC) ratio r=0.613 p<0.001.Summary/Conclusion:Several clinical and biological biomarkers haverecently been proposed to stratify sMM patients on their risk of progressionto symptomatic disease. Based on the positive correlation between LIGHTexpression levels on circulating monocytes, and involved/uninvolved serumFLC ratio, we could argue that LIGHT may be further assessed as a potentialbiological precursor of lytic bone-disease development in sMM patients.Reliable clinical and biological biomarkers for risk stratification of sMM can allow to plan optimized follow-up as well as to identify further sub-groups of patients, who could benefit from an early treatment. The highlevels of LIGHT expressed by circulating monocytes and their correlationwith FLC ratio, suggest a possible role of this cytokine as biological predictorof sMM progression to symptomatic MM