key: cord-0848310-z47sbs8h
authors: Aroldi, Andrea; Chiarle, Roberto; Gambacorti-Passerini, Carlo
title: Clinical Benefit of Lenzilumab in Cases of Coronavirus Disease 2019
date: 2021-01-11
journal: Mayo Clin Proc
DOI: 10.1016/j.mayocp.2020.12.030
sha: 9e1d702051eba6dcd58bb9e9bdfa2472bac0f2a7
doc_id: 848310
cord_uid: z47sbs8h

nan

To the Editor: Temesgen et al 1 host monocyte-macrophage system is the major source of cytokine production (e.g. interleukin (IL)-1 and IL-6). 2 In this setting, Lenzilumab showed to be effective in reducing CAR T-mediated CRS and neuroinflammation at the same time, enhancing adoptive T cell therapy as well. 3 Previous preclinical data in SARS-CoV infected mice showed that inflammatory monocyte-macrophage response, secondary to dysregulated type-I interferon activity during SARS-CoV infection, results in lethal pneumonia and cytokine-induced apoptosis of T cells (specifically mediated by tumor necrosis factor alpha -TNF-α). 4

As already known, GM-CSF inhibition turned out to broadly modulate monocytemacrophage activity by simultaneously reducing a spectrum of inflammatory cytokines, including TNF-α. 3 We therefore suggest that the direct regulation of monocytemacrophage activity by Lenzilumab, with subsequent broad cytokines shutdown, could provide a more favorable micro-environment where effector T cells could also be protected from cytokine-induced apoptosis. This would preserve a non-exhausted T cell phenotype, being more effective against infections and performing more potently T cell specific antiviral immunity to achieve viral clearance.

Aware of the good safety profile of Lenzilumab in this current study and previous analysis, 1,5 the treatment is feasible and safe and the ongoing randomized phase III trial (NCT04351152) will extensively confirm the lymphocyte recovery in Sars-CoV-2 infection and the impact of the drug on COVID-19 clinical improvement.

Andrea Aroldi, MD San Gerardo Hospital University of Milano-Bicocca Monza, Italy

GM-CSF Neutralization With Lenzilumab in Severe COVID-19 Pneumonia: A Case-Cohort Study

Harnessing CAR T-cell Insights to Develop Treatments for Hyperinflammatory Responses in Patients with COVID-19

GM-CSF inhibition reduces cytokine release syndrome and neuroinflammation but enhances CAR-T cell function in xenografts

Dysregulated Type I Interferon and Inflammatory Monocyte-Macrophage Responses Cause Lethal Pneumonia in SARS-CoV-Infected Mice

Phase 1 study of lenzilumab, a recombinant anti-human GM-CSF antibody, for chronic myelomonocytic leukemia