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Leo I. Gordon, MD, FACP


SITC 2022: Identifying Markers for Grade 3 Toxicities in Patients With LBCL Treated With Axicabtagene Ciloleucel

By: Joseph Fanelli
Posted: Friday, November 18, 2022

Findings presented at the 2022 Society for Immunotherapy of Cancer (SITC) Annual Meeting (Abstract 687) attempted to identify potential markers linked to the development of high-grade toxicities for patients with relapsed or refractory large B-cell lymphoma (LBCL) and follicular lymphoma who receive axicabtagene ciloleucel. Frederick Locke, MD, of the Moffitt Cancer Center, Tampa, Florida, and colleagues also observed that pretreatment markers such as serum levels of lactate dehydrogenase, interleukin-6 (IL-6), and IL-5 had positive associations with grade 3 cytokine-release syndrome and neurologic events after treatment with this anti-CD19 chimeric antigen receptor (CAR) T-cell therapy.

“Safety of CAR T-cell therapy may be improved by optimization of product or conditioning regimen to reduce adverse event–dependent proinflammatory activities while maintaining efficacy,” the authors said.

In this analysis, the authors collected serum samples from 142 patients in the ZUMA-1 phase II trial. All patients were diagnosed with relapsed or refractory LBCL or follicular lymphoma. The samples were collected before conditioning chemotherapy and CAR T-cell therapy. The authors tested the association between marker expression and early grade 3 toxicities using the Wilcoxon test and logistic regression as well as weighted gene coexpression network analysis (WGCNA) to identify highly coexpressed protein clusters.

Following CAR T-cell infusion, 24 patients (17%) experienced grade 3 cytokine-release syndrome and/or neurologic events. Univariate and WGCNA analyses revealed clusters of pretreatment markers were associated with these toxicities and revealed these clusters had positive correlations with poor prognostic factors. Additional analysis of these clusters demonstrated enrichment of proteins involved in the metabolic processes and leukocyte activation.

In addition, the authors noted that IL-1 and IL-6 pathway markers may prove to be helpful in identifying grade 3 cytokine-release syndrome. Moreover, inflammatory endothelial markers (eg, ACE2, CEACAM1, ICAM2, and ADAM15) may be used to classify patients with both grade 3 cytokine-release syndrome and neurologic events after treatment with axicabtagene ciloleucel.

Disclosure: No information regarding conflicts of interest was provided.

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