Inhibition of Bruton tyrosine kinase in patients with severe COVID-19

COVID-19 is an efficient killer in chronic lymphocytic leukemia (CLL) patients. While most patients recover, those who develop an exaggerated inflammatory response to the infection seem to be the ones who end up on supplement oxygen, in the ICU, on ventilators and too often end up not making it.

There is now research to support that activation of BTK may play a critical role in the development of the downhill inflammatory cascade seen in those patients with more severe disease.

To be clear, this is completely independent of BTK’s role in supporting the life and growth of CLL cells.

Now acalabrutinib and ibrutinib, both potent BTK blockers, are being investigated “off label” as possible therapies for COVID-19 patients who do not have CLL and should have a normal immune system.

While this substantial peer-reviewed published report of a trial of acalabrutinb is not a controlled study, the results of those who received a standard dose of acalabrutinb are very encouraging:

• Inflammatory markers that shoot up when the patients start to deteriorate seem to come down significantly with acalabrutinib.
• 8 of 11 or 73% of patients who had been on oxygen therapy no longer required supplemental oxygen and were able to be discharged from the hospital.
• 4 of 8 were able to get off their ventilator.

Here is a link to the rather technical research on Inhibition of Bruton tyrosine kinase in patients with severe COVID-19 published in Science Immunology that provides much more detail.

This report comes on top of the data of COVID-19 outpatients taking ibrutinib for Waldenstrom’s Macroglobulinemia we reported on last week. Together they suggest that this might be a real lead in helping COVID-19 patients. These data support the idea behind the CALAVI-US trial which is already underway to investigate acalabrutinib as a potential treatment for patients with life-threatening COVID-19 symptoms.

We will keep you updated as the research evolves.

Stay strong.  We are all in this together.

Brian

Brian Koffman MDCM (retired) MS Ed
Co-Founder, Executive VP and Chief Medical Officer
CLL Society, Inc.