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Leo I. Gordon, MD, FACP


SITC 2022: Anakinra Prophylaxis and Toxicity of Axicabtagene Ciloleucel in Resistant LBCL

By: Gavin Calabretta, BS
Posted: Tuesday, November 15, 2022

Findings presented at the 2022 Society for Immunotherapy of Cancer (SITC) Annual Meeting (Abstract 301) identified several molecular pathways and immune cell populations believed to be modulated by the recombinant interleukin-1 receptor antagonist anakinra. According to Ning Yao, MS, of The Broad Institute, Cambridge, Massachusetts, and colleagues, anakinra—which has been suggested to manage toxicity in B-cell malignancies by previous animal studies—appeared to modulate interleukin (IL) signaling pathways in certain T-cell populations and influence the proportion of regulatory T cells.

“The wider utilization of CAR-T [chimeric antigen receptor T-cell therapy] is limited by CAR-T–induced adverse events including cytokine-release syndrome,” the researchers commented. They leveraged single-cell RNA sequencing to analyze the pathways altered by anakinra and the potential mediators of breakthrough cytokine-release syndrome cases.

The phase II trial tested the use of prophylactic anakinra in patients with relapsed or refractory large B-cell lymphoma (LBCL) who were eligible to receive axicabtagene ciloleucel as per the ZUMA-1 registration study. The investigators sequenced the peripheral blood mononuclear cells of 10 patients 7 days after infusion, along with the infusion products. Results were compared with 4 control samples, as well as 19 other patients who were treated with axicabtagene ciloleucel but without anakinra prophylaxis.

The authors observed that IL-4 and IL-10 anti-inflammatory pathways were negatively associated with breakthrough cytokine-release syndrome in the infusion products of both the anakinra and non-anakinra cohorts. The same pathways appeared to be enriched in anakinra-treated CAR-positive, CD4-positive T-cell populations, and anakinra prophylaxis was additionally associated with an increased proportion of CAR-positive regulatory T cells. Moreover, in patients who received tocilizumab in addition to anakinra, expression of interferon gamma pathways, along with cytokine levels of interferon gamma and interferon gamma–induced protein 10 in CD14-positive monocytes, was enriched in patients with breakthrough cytokine-release syndrome. This enrichment, according to the researchers, suggests that interferon gamma may be targetable but is not inhibited by anakinra alone.

Disclosure: No disclosure information was provided.

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