To The Editor:
We thank Dr Aroldi and colleagues 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 severe acute respiratory syndrome coronavirus 2 through modulation of monocyte-macrophage 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 monocyte-macrophage 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 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 the ACTIV-5/Big Effect Trial sponsored by the National Institutes of Health which will determine if the combination of lenzilumab and remdesivir is superior to remdesivir alone (NCT04583969). This trial is now actively enrolling patients.
Footnotes
Potential Competing Interests: The authors report no potential competing interests.
References
- 1.Temesgen Z., Assi M., Shweta F.N.U. GM-CSF Neutralization with lenzilumab in severe COVID-19 pneumonia: a case-cohort study. Mayo Clin Proc. 2020;95(11):2382–2394. doi: 10.1016/j.mayocp.2020.08.038. [DOI] [PMC free article] [PubMed] [Google Scholar]
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- 4.Humanigen announces positive interim phase 3 data of lenzilumab™ in patients hospitalized with COVID-19 [Press release] Humanigen, Inc; Burlingame, CA: November 6, 2020. [Google Scholar]