key: cord-1056264-fhduogci
authors: Temesgen, Zelalem; Kenderian, Saad S.; Badley, Andrew D.
title: In Reply - Clinical Benefit of Lenzilumab in Cases of Coronavirus Disease 2019
date: 2021-01-11
journal: Mayo Clin Proc
DOI: 10.1016/j.mayocp.2020.12.029
sha: c3388569627db5d3a7f6990fe1706bc6da08f4f2
doc_id: 1056264
cord_uid: fhduogci

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We thank Aroldi et al. for their letter in response to our manuscript "GM-CSF Neutralization with Lenzilumab in Severe COVID-19 Pneumonia: A Case-Cohort Study". 1 We agree that lenzilumab may benefit patients with SARS-CoV-2 through modulation of monocytemacrophage activity by reducing a spectrum of hyperinflammatory cytokines. We are also intrigued by the observation that lenzilumab may improve lymphocyte counts. Although the mechanism remains to be elucidated in full, we have observed improved lymphocyte proliferation and lymphocyte effector function in preclinical models with lenzilumab. 2, 3 We agree that modulation of the monocytemacrophage activity may provide a more favorable micro-environment for T cells resulting in reduced apoptosis.

We look forward to replicating the positive signal in clinical and laboratory markers as well as the excellent safety profile of lenzilumab that we noted in our study being in the ongoing randomized phase 3 clinical trial (NCT04351152). This phase 3 trial is now 80% enrolled and a recent interim analysis was favorable with lenzilumab showing clinical benefit over and above concomitant dexamethasone and remdesivir. 4 We also look forward to results from ACTIV-5/Big Effect Trial (BET) sponsored by the NIH which will determine if the combination of lenzilumab and remdesivir is superior to remdesivir alone (NCT04583969). This trial is now actively enrolling patients.

J o u r n a l P r e -p r o o f

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

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

Improved Anti-Tumor Response of Chimeric Antigen Receptor T Cell (CART) Therapy after GM-CSF Inhibition Is Mechanistically Supported By a Novel Direct Interaction of GM-CSF with Activated Carts

Humanigen announces positive interim phase 3 data of lenzilumab™ in patients hospitalized with COVID-19