Ibrutinib and Acalabrutinib for COVID-19

There has been a significant buzz about the possibility that two drugs approved to treat chronic lymphocytic leukemia (CLL) might also help those with COVID-19, specifically those with significant breathing issues requiring supplemental oxygen and mechanical ventilation.

It is thought in patients with severe distress when infected with the novel coronavirus, SARS-CoV- 2, that much of the potentially fatal lung damage is not directly a result of the virus itself, but rather from the body’s overly vigorous immune response to the virus. For more on this research, see this from Lancet.

There are many theoretical reasons and some good animal studies that suggests it’s sensible to consider exploring whether acalabrutinb (Calquence) and ibrutinib (Imbruvica) would work in very sick COVID patients.

Both BTK inhibitors work in CLL by blocking an enzyme called Bruton Tyrosine Kinase or BTK. BTK is part of the B cell receptor or BCR pathway. CLL cells are addicted to stimulation from the BCR and turning it off, turns off the cancer cells and they eventually die.

But both drugs do more than inhibit BTK. They have so called off target effects that block other kinases or enzymes such as HCK. This in turn, at least theoretically, might dampen the immune system and prevent severe lung damage.

Ibrutinib is already being used in other over-active inflammatory conditions, such as graft versus host disease that can be seen after a bone marrow transplant, and also to calm the cytokine release syndrome (CRS) or cytokine storm seen post CAR-T treatments. It has been shown to reduce the infusion related reactions associated with obinutuzumab, which are another type of CRS.

We now believe severe CRS also contributes to the morbidity and mortality of infections with SARS-CoV- 2 and calming CRS may save lives as it does post CAR-T.

Now we have some encouraging human data that it might do just that in patients on ibrutinib for a related B cell cancer, Waldenstrom’s Macroglobulinemia from this correspondence (with thanks to ASH publication, BLOOD) by Dr. Treon published in Blood. Only 6 patients, but promising.

So now let’s do bigger controlled prospective studies and see if it really does help.

Here is a link to the article in Forbes that interviews two major CLL researchers, Dr. Byrd and Sharman on just such trials.

And here is the press release from AstraZeneca  about their trial with acalabrutinib.

Will it work? Looks as if we are going to find out.

Stay strong. We are all in this together.

Brian