To the Editor:
We have read with interest the article published in CHEST (January 2021) by Patel et al1 in which the authors present a single case of cytokine storm due to coronavirus disease 2019 (COVID-19) treated with etoposide. The authors claim that this is the first report of a severe acute respiratory syndrome coronavirus 2-related hyperinflammatory state treated with topoisomerase II inhibitor etoposide. However, we previously reported on 11 patients with COVID-19 who presented with hyperinflammation treated with etoposide as salvage therapy.2 In our experience, just one to two doses of etoposide (50-150 mg/m2) were clinically effective and resulted in a significantly decreased need for intubation in the majority of patients from a selected cohort with alarming Pao 2/Fio 2 ratios, commonly under 150. We advocate for administering etoposide to patients with biochemical alterations suggestive of severe hyperinflammation (ferritin levels >1000 ng/mL and/or IL-6 values >50 pg/mL), acute respiratory distress syndrome (defined by Pao 2/Fio 2 <300), and failure of previous treatment with methylprednisolone (or dexamethasone) plus tocilizumab or anakinra. After treatment, we observed a rapid and nearly 200% overall improvement of Pao 2/Fio 2 ratios; >80% of the patients finally could be discharged home. We also observed three cases of profound leukopenia. However, hepatotoxicity was not relevant in our series. All patients had received methylprednisolone and interleukin inhibitors before etoposide, which could have been potential confounders in the interpretation of results. At present, etoposide is offered to patients who present with cytokine storm release syndrome resembling that of hemophagocytic lymphohistiocytosis, in which corticoid plus interleukin inhibitor treatment fails to improve the clinical course, as part of our institutional therapeutic protocol for COVID-19. The currently ongoing clinical trial3 that started on May 8, 2020 will likely contribute to evaluate the safety and efficacy of etoposide in these patients.
Footnotes
FINANCIAL/NONFINANCIAL DISCLOSURES: None declared.
References
- 1.Patel M., Dominguez E., Sacher D., et al. the Temple University COVID-19 Research Group. Etoposide as salvage therapy for cytokine storm due to coronavirus disease 2019. Chest. 2021;159(1):e7–e11. doi: 10.1016/j.chest.2020.09.077. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 2.Montero-Baladía M., Buzón L., Astigarraga I., et al. Etoposide treatment adjunctive to immunosuppressants for critically ill COVID-19 patients. J Infect. 2020;81(3):452–482. doi: 10.1016/j.jinf.2020.06.006. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 3.National Institutes of Health Clinical Center. Etoposide in patients with COVID-19 infection. NCT04356690. ClinicalTrials.gov. National Institutes of Health; 2020. Updated January 5, 2021. https://clinicaltrials.gov/ct2/show/NCT04356690.