Impact Of Il-1 Beta And The Il-1r Antagonist On Relapse Risk And Survival In Aml Patients Undergoing Immunotherapy For Remission Maintenance

Interleukin-1 beta (IL-1 beta), a pro-inflammatory cytokine, has been ascribed a role in the expansion of myeloid progenitors in acute myeloid leukemia (AML) and in promoting myeloid cell-induced suppression of lymphocyte-mediated immunity against malignant cells. This study aimed at defining the potential impact of IL-1 beta in the post-remission phase of AML patients receiving immunotherapy for relapse prevention in an international phase IV trial of 84 patients (ClinicalTrials.gov; NCT01347996). Consecutive serum samples were collected from AML patients in first complete remission (CR) who received cycles of relapse-preventive immunotherapy with histamine dihydrochloride (HDC) and low-dose interleukin-2 (IL-2). Low IL-1 beta serum levels before and after the first HDC/IL-2 treatment cycle favorably prognosticated leukemia-free survival and overall survival. Serum levels of IL-1 beta were significantly reduced in patients receiving HDC/IL-2. HDC also reduced the formation of IL-1 beta from activated human PBMCs in vitro. Additionally, high serum levels of the IL-1 receptor antagonist IL-1RA were associated with favorable outcome, and AML patients with low IL-1 beta along with high IL-1RA levels were strikingly protected against leukemic relapse. Our results suggest that strategies to target IL-1 beta might impact on relapse risk and survival in AML.