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June 16, 2020
Cancer drug may reduce symptoms of severe COVID-19
At a Glance
- Early data showed that off-label use of a cancer drug reduced respiratory distress and over-reactive immune responses in patients with COVID-19.
- Based on these results, researchers have designed a clinical trial to test whether the drug can be used as a safe and effective treatment for patients with COVID-19.
Coronavirus disease 2019 (COVID-19), which is caused by the virus SARS-CoV-2, is a respiratory illness that can bring mild to severe symptoms. These often include fever, cough, and shortness of breath. Some patients with severe COVID-19 have a hyper immune system response. The immune system normally protects your body from microscopic infections, like bacteria and viruses, by attacking the infection. But an exaggerated immune response can damage the function of your organs, such as the lungs.
This dangerous hyperinflammatory state in patients with severe COVID-19 is known as a cytokine storm. Cytokines act as chemical messengers that help to stimulate and direct the immune response. But when large amounts of cytokines are released in the body, it can be dangerous. Currently, there are no proven treatment strategies for this phase of the illness.
The Bruton tyrosine kinase (BTK) protein plays an important role in the immune system response. Macrophages, a type of immune cell, use BTK to produce cytokines and inflammation. BTK inhibitors are approved to treat certain cancers, but they are not approved as a treatment for COVID-19.
A research team led by Drs. Wyndham H. Wilson, Louis M. Staudt, and Mark Roschewski at NIH’s National Cancer Institute (NCI) and Mihalis Lionakis at NIH’s National Institute of Allergy and Infection Diseases (NIAID) tested the off-label use of a BTK inhibitor called acalabrutinib to treat COVID-19. They carried out a clinical study of 19 patients with a confirmed COVID-19 diagnosis who required hospitalization and had low blood-oxygen levels and evidence of inflammation. Of these, 11 had been receiving supplemental oxygen for a median of two days, and eight others had been on ventilators for a median of 1.5 days.
The study, which was funded by NCI and NIAID, was done in collaboration with researchers at the U.S. Department of Defense’s Walter Reed National Military Medical Center and four other hospitals nationally. Results were published on June 05, 2020 in Science Immunology.
Within one to three days after receiving acalabrutinib, the majority of patients receiving supplemental oxygen experienced a substantial drop in inflammation, and their breathing improved. Eight of these 11 patients were able to come off supplemental oxygen and were discharged from the hospital. Four of the eight patients who were on a ventilator were able to come off it, and two were eventually discharged. Two of the patients in this group died.
Blood samples from the patients showed that levels of interleukin-6 (IL-6), a major cytokine associated with hyperinflammation in severe COVID-19, decreased after treatment with acalabrutinib. Counts of lymphocytes, a type of white blood cell, also rapidly improved in most patients. Low lymphocyte counts have been associated with worse outcome for patients with severe COVID-19.
The researchers compared blood cells from healthy volunteers and patients with severe COVID-19 who were not in the study. Those from patients with COVID-19 had higher activity of the BTK protein and greater production of IL-6.
“If these results are confirmed by a randomized, controlled clinical trial, this therapy may play an important role in the control of severe COVID-19,” Wilson says.
“We have been successfully treating lymphoma patients with BTK inhibitors for years and were eager to lend our expertise to help address the global COVID-19 pandemic,” Staudt adds.
The results of this study were used to inform the design of a clinical trial to further investigate the drug’s safety and efficacy.
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- Coronavirus (COVID-19)
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References: Inhibition of Bruton tyrosine kinase in patients with severe COVID-19. Roschewski M, Lionakis MS, Sharman JP, Roswarski J, Goy A, Monticelli MA, Roshon M, Wrzesinski SH, Desai JV, Zarakas MA, Collen J, Rose K, Hamdy A, Izumi R, Wright GW, Chung KK, Baselga J, Staudt LM, Wilson WH. Sci Immunol. 2020 Jun 5;5(48):eabd0110. doi: 10.1126/sciimmunol.abd0110. Epub 2020 Jun 5. PMID: 32503877.
Funding: NIH’s National Cancer Institute (NCI) and National Institute of Allergy and Infectious Diseases (NIAID).