Role of Serum Free Light Chain Assay in Relapsed/Refractory Multiple Myeloma. A Real-Life Unicentric Retrospective Study

SIMPLE SUMMARY: According to the International Myeloma Working Group diagnostic criteria serum free light chain (sFLC) assay is recommended for disease monitoring in oligo-secretory and micromolecular multiple myeloma (MM). However, normo-secretory patients could suffer from oligo-secretory/micromolecular escape at disease relapse, making it difficult to monitor disease relapse with serum protein electrophoresis alone. The possibility of a simple and manageable biochemical exam able to predict either future treatment response at disease relapse or relapse type in the course of treatment could be of great aid. In this work, we retrospectively analyzed the occurrence of oligo-secretory/micromolecular escape at disease relapses and its impact on disease outcome. Moreover, we have retrospectively evaluated the role of sFLC ratio and involved sFLC at disease relapse in a historical real-life single-center cohort of MM patients that underwent at least three lines of treatment. ABSTRACT: Background: In the era of novel drugs a growing number of multiple myeloma (MM) patients are treated until disease progression. Serum free light chain (sFLC) assay is recommended for disease monitoring in oligo-secretory and micromolecular MM. Methods: In this real-life survey, a total of 130 relapsed/refractory MM patients treated at our center with at least three lines were investigated as a retrospective cohort. Results: The median age at diagnosis was 64 years and more than half of patients were male. A total of 24 patients (18%) had oligo-secretory/micromolecular disease at diagnosis. More than 20% of 106 normo-secretory patients had oligo-secretory/micromolecular escape. In order to evaluate potential role of sFLC assay before (“pre”) and after (“post”) every treatment line, involved serum free light chain values (iFLC) less than 138 mg/mL and serum free light chain ratios (FLCr) <25 were identified by using ROC curve analysis. The analysis of the entire cohort throughout four treatment lines demonstrated a statistically significant negative impact on progression-free survival (PFS) for both involved pre-sFLC and its ratio (respectively p = 0.0086 and p = 0.0065). Furthermore, both post-iFLC and post-FLCr greater than the pre-established values had a negative impact on PFS of the study cohort; respectively, p = 0.014 and p = 0.0079. Odds ratio analysis evidenced that patients with both involved post-sFLC greater than 138 mg/mL and post-FLCr above 25 at disease relapse had a higher probability of having clinical relapse (respectively p = 0.026 and p = 0.006). Conclusions: Alterations of sFLC values, namely iFLC and FLCr, both prior to treatment initiation and in the course of therapy at every treatment line, could be of aid in relapse evaluation and treatment outcome. We therefore suggest close periodical monitoring of sFLC assay, independently from secretory status.