Managing Inflammation in Chronic Lymphocytic Leukemia Treatment

Clinical trials for lenalidomide as a treatment for chronic lymphocytic leukemia (CLL) were halted by the FDA due to safety concerns involving higher death rates. Tumor flare inflammatory reactions occurred in 30% of patients in one study. In patients that did not respond to lenalidomide treatment, IL-6 was significantly increased. In contrast, lenalidomide, approved for use with multiple myeloma, decreases IL-6. In the experiment reported here, natural killer (NK) cells and chronic lymphocytic leukemia cells were treated with lenalidomide and QNZ which inhibits NF-κB, a transcription factor that enhances transcription of IL-6. A potential new therapeutic option in CLL patients may be to administer lenalidomide and QNZ to treat the cancer while inhibiting NF-κB which would lead to decreased levels of IL-6. Results of this study demonstrate a statistically significant decrease in IL-6 in a NK and CLL co-culture as compared to treatment with lenalidomide alone (p<0.05). In non-treated co-cultures, there was a statistically significant decrease in viable cells compared to individual culture, indicating cytotoxicity and efficacy as a chemotherapeutic regime (p<0.05). NK cell viability determined through CD56 labelling showed a significant increase when cells were treated with both lenalidomide and QNZ as opposed to lenalidomide alone (p<0.05).