A phase I trial of the IL1-receptor antagonist anakinra in previously untreated CLL patients at risk for progression

Inflammatory factors that activate NFkB play an important role in the pathogenesis of chronic lymphocytic leukemia (CLL) but are not addressed specifically by current therapies. Interleukin-1 (IL-1) is a master-regulator of inflammation that is inhibited safely in humans by the IL-1 receptor antagonist anakinra. Anakinra was found to inhibit NFkB activity in CLL cells in an IL-1 receptor independent manner and had properties of an intracellular anti-oxidant in vitro. A phase I dose-escalation trial in 11 previously untreated CLL patients (NCT04691765) indicated anakinra was safe at doses up to 400 mg daily and produced transient clinical responses associated with down-regulation of NFkB and oxidative stress in circulating CLL cells in vivo. However, type 1 interferon (IFN)-signaling and c-MYC-regulated genes and proteins were induced at the same time. Overall design: CLL cells were purified before starting anakinra (C1D1) and after 2 weeks on treatment with anakinra (C1D14). Bulk RNA seqeuencing was performed to compare gene expression at the two time-points.