Altered cytokine profiles in multiple myeloma (MM) and precursor disease: Predictors of progression and potential targets for treatment.

Abstract

8597 Background: Presently, there is no reliable biomarker for predicting clinical progression from smoldering (SMM) to symptomatic MM for individual patients. To improve our understanding on the pathogenesis from SMM to MM, we conducted a screening study of circulating cytokines using peripheral blood (PB) and bone marrow supernatant (BM) collected from treatment naïve SMM and MM patients as well as healthy donors as controls. Methods: PB samples from 14 SMM and 38 MM patients and 7 controls and BM obtained from 17 MM patients and 9 controls were assayed in duplicates using ultra-sensitive Human TH1/TH2 10-plex multi-spot plate and multi-array plate for interleukin-(IL)-6. Two-tailed Mann-Whitney test was used for statistical analysis. Results: PB of SMM patients (vs controls) had increased levels of several cytokines, including IL-8 (p=0.008) and IFN-gamma (p=0.002). In PB, MM patients (compared to SMM patient and controls) had increased levels of IL-6 (p=0.006 and 0.001, respectively), IL-8 (p=0.0001 and 0.008), IL-10 (p=0.02 and 0.02), TNF-alpha (p=0.01 and 0.009), and IFN-gamma (p=0.01 and 0.02). Analysis of BM revealed a similar profile with increased levels of IL-2, IL-6, IL-8, and TNF-alpha in MM patients compared with controls (p=0.007, p=0.0003, p=0.0001 and p=0.0008). Conclusions: We found significantly increased levels of key cytokines associated with progressive disease state (controls→SMM→MM). Patterns of cytokines were similar in BM and PB, suggesting that serum based cytokines may have a future role as biomarkers for disease progression, and could potentially be assessed as novel targets for treatment.