Preliminary investigation into the association of serum free kappa light chains with risk stratification, clonal evolution and precision therapy in multiple myeloma

Multiple myeloma (MM) is a highly heterogeneous plasma cell malignancy whose progression and relapse are influenced by clonal heterogeneity. Although serum free light chains (sFLCs) are key biomarkers for tumour burden assessment, the clinical value of λ, κ and their ratio remains controversial. This study investigated the associations of sFLC κ, λ and the κ/λ ratio with clinical features, cytogenetic abnormalities, prognosis and response to the VRd regimen (bortezomib, lenalidomide, dexamethasone) in newly diagnosed MM (NDMM) patients, aiming to optimize risk stratification. A retrospective analysis of 113 NDMM patients was conducted. Baseline clinical data, cytogenetic markers (RB1/D13S319/IGH/1q21/P53/1p32) and treatment responses were collected, with stratification by renal function. Tumour proliferation, apoptosis and angiogenesis were assessed by immunohistochemistry. Prognostic factors were evaluated using Kaplan-Meier and Cox regression analyses. A modified revised International Staging System (R-ISS) (MR-ISS) model incorporating sFLC κ was then developed and temporally externally validated. Abnormal sFLC κ indicated poor prognosis. Among NDMM patients with normal renal function, abnormal sFLC κ was significantly associated with adverse clinical features, high tumour burden, an anti-apoptotic and angiogenic tumour microenvironment, D13S319 deletion and a lower rate of deep remission after VRd induction. Moreover, the MR-ISS model demonstrated superior risk discrimination compared with the R-ISS. In conclusion, abnormal sFLC κ is a potential marker of poor prognosis and suboptimal response to VRd therapy in NDMM. Integrating sFLC κ with the R-ISS improves risk stratification, providing new evidence for clinical application of this biomarker.