Acalabrutinib, a Bruton tyrosine kinase (BTK) inhibitor, may be beneficial in the treatment of patients hospitalized with advanced COVID-19, according to the results of a small study presented at the American Association of Cancer Research (AACR) Virtual Meeting: COVID-19 and Cancer.
The BTK inhibitor, acalabrutinib, has been approved by the US Food and Drug Administraion (FDA) for the treatment of adult patients with some B-cell malignancies, including mantle cell lymphoma, chronic lymphocytic leukemia, and small cell lymphoma.2
Some of the rationales for using a BTK inhibitor to treat patients with moderate/severe SARS-CoV-2 infection included evidence of systemic inflammation associated with later stages of COVID-19, as well as the ability of BTK inhibitors to block BTK signaling in innate immune cells, such as macrophages/moncytes, that is associated with “cytokine storm” and a hyperinflammatory response, according to Mark Roschewski, MD, senior clinician at the Lymphoid Malignancies Branch of the National Cancer Institute Center for Cancer Research in Bethesda, Maryland, the lead author of this study.
In this single-arm study, emergency use of acalabrutinib was made available to hospitalized patients with moderate/severe COVID-19 through the Monitored Emergency Use of Unregistered and Investigational Interventions (MEURI) guidelines from the World Health Organization (WHO).
Study enrollment criteria specified that patients must be hospitalized with confirmed COVID-19-associated hypoxemia with an oxygen saturation less than 94%, and also show evidence of systemic inflammation, such as a serum ferritin level above 500 ng/mL or a serum C-reactive protein (CRP) level greater than 10 mg/dL. Study endpoints included the rates of mechanical ventilation and death, as well as the safety of acalabrutinib in these patients.
Of the 19 patients treated with acalabrutinib at a dose of 100 mg twice daily for 10 to 14 days, along with best supportive care, 11 patients received supplemental oxygen and 8 underwent mechanical ventilation.
Study findings showed that for non-intubated patients, blood oxygen saturation and lymphocyte level, with lymphopenia as another marker of inflammation, increased along with a corresponding decrease in serum CRP level following 1 to 3 days of treatment with acalabrutinib.
“This temporal association with the delivery of the drug made us feel that this is likely due to the drug although, of course, this was not a controlled trial,” Dr Roschewski noted.
Regarding these markers, some of the patients undergoing mechanical ventilation responded similarly to most of the nonintubated patients, although others did not.
Specifically, in the supplemental oxygen group, 9 patients were discharged to home on room air, 1 patient continued to receive supplemental oxygen at a rehabilitation facility, and 1 patient died. In the group receiving mechanical ventilation, 4 patients died with 3 patients discharged to home on room air and 1 patient w discharged to a rehabilitation facility where they required supplemental oxygen.
No serious acalabrutinib-associated toxicity was observed in the overall group of patients.
In his concluding remarks, Dr Roschewski, noted that “acalabrutinib was beneficial for patients with severe COVID-19,” with “greater efficacy seen in patients receiving supplemental oxygen.”
Nevertheless, he added that “these results need confirmation in a randomized, double-blind, placebo-controlled trial.”
A randomized, open-label, phase 2 study of acalabrutinib plus best supportive care compared with best supportive care alone (ClinicalTrials.gov Identifier: NCT04380688) is currently enrolling patients hospitalized with COVID-19.
- Roschewski M, Sharman JP, Roswarski J, et al. Inhibition of Bruton tyrosine kinase in patients with severe COVID-19. Presented at: American Association for Cancer Research (AACR) Virtual Meeting: COVID-19 and Cancer. July 20-22, 2020.
- Acalabrutinib (Calquence®) [package insert]. Wilmington, DE: AstraZeneca Pharmaceuticals LP, 2019.