Cytokine profile in multiple myeloma

Abstract

Background Cytokines play a crucial role in the growth, survival and dissemination of malignant plasma cells in patients of multiple myeloma (MM). We estimated concentrations of five key cytokines: Vascular Endothelial Growth Factor (VEGF), Interleukin-6 (IL-6), Tumor Necrosis Factor- alpha (TNF- α), B-cell activating factor (BAFF), and Receptor Activator of Nuclear Factor-κB ligand (RANKL) in newly diagnosed and relapsed/refractory MM (RRMM). Methods The study groups include 68 newly diagnosed and 21 relapsed/refractory (RR) MM patients. 32 out of 68 newly diagnosed MM patients were evaluated for serum cytokine concentrations after their treatment. For survival analysis, the various parameters were studied in relation to both progression free survival (PFS) and overall survival (OS). Results The median serum levels of VEGF, IL-6, BAFF and RANKL were higher in RRMM compared with newly diagnosed patients. However, the difference was significant for BAFF levels (p = 0.04). The median serum levels of VEGF, IL-6, TNF-α, BAFF and RANKL were significantly higher in newly diagnosed and RRMM patients, compared to controls. We also observed lower plasma levels of VEGF (p≤0.0001) and BAFF (p≤0.0001) in BM compartment compared to the levels in serum from peripheral blood of newly diagnosed patients. Significant reduction in the median levels of IL-6, TNF-α, BAFF and RANKL was seen after 4–6 cycles of induction treatment in responders but not in non-responders. On survival analysis, RRMM patients had inferior median OS and PFS compared to that in newly diagnosed MM patients and found to be significantly associated with low haemoglobin representing the more aggressive disease biology in recurrent myeloma. The mean levels of IL-6 were significantly different in patients who died as compared to patients who were alive. Conclusions The present study demonstrates that the serum levels of VEGF, IL-6, TNF, BAFF and RANKL are significantly elevated and decrease significantly after treatment. The concentrations of circulating cytokines will reflect those of the bone marrow and could be used for subsequent analyses.