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BTK inhibitors – do they have a role to play in reducing the impact of COVID-19?

BTK Inhibitors
Research amongst WM patients with COVID-19 shows interesting findings.
There is a suggestion that BTK inhibitors such as ibrutinib, acalabrutinib and zanubrutinib may provide favourable suppression of the immune system resulting in the reduction of inflammatory damage to the lungs due to COVID-19 - the so-called cytokine release syndrome (CRS).

Professor Steven Treon and his team at the Bing Center for Waldenstrom’s macroglobulinaemia at the Dana Farber Cancer Institute in Boston, USA, illustrated this in a letter to the Editor of Blood (American Society of Hematology medical journal) that was pre-published over the weekend:

https://ashpublications.org/blood/article/doi/10.1182/blood.2020006288/454437/The-BTK-inhibitor-ibrutinib-may-protect-against

Professor Treon and his team presented six cases of COVID-19 patients with Waldenstrom’s macroglobulinaemia who were on full-dose ibrutinib. Five of those patients overcame their COVID-19 disease with no shortness of breath or low blood oxygen levels. Another patient who was on a reduced dose of ibrutinib stopped taking the drug and required breathing support on a ventilator. While on the ventilator, the patient was given full doses of ibrutinib, which was mixed with water, through a nasogastric tube. Within two days, the patient was off the ventilator and then went home.

To summarise, the key scientific points are:

  1. Coronaviruses have been shown to cause lung injury via the response of the immune system to the infection which includes the release of a range of inflammatory chemicals (cytokines).
  2. Such proteins have been shown to promote lung injury in laboratory animals. The findings on the lungs of these animal are similar to that seen in COVID-19 patients’ lungs.
  3. Over-production of certain inflammatory proteins (including BTK) are typical in WM and form the basis for the use of BTK inhibitors.
  4. Since BTK inhibitors block this inflammatory pathway, the damaging inflammatory activity seen in the lungs of COVID-19 infected patients could be limited by ibrutinib and similar drugs.

The extent to which this can reliably be expected in individual patients is not clear, hence the setting up of trials of these agents in COVID-19 patients. At present, these trials are not yet open in the UK, although communications are underway to enable UK participation.

A number of WM patients in the UK are already on BTK inhibitors (including ibrutinib, acalabrutinib and zanubrutinib, the latter two agents only in clinical trials). The guidance at this time is for patients who are affected by COVID-19 whilst on these treatments to continue to take them if at all possible.

Those who are not currently receiving these agents will not be able to be converted to BTK inhibitors solely for the purpose of improving a COVID-19 infection or started on them solely as protection against COVID-19 as it has not yet been confirmed that these agents are protective.

WMUK will be keeping a close eye on events as they evolve and will make it a priority to ensure that UK patients are able to take up any opportunities that arise from this research.

 

Dr Shirley D’Sa
WMUK trustee
Consultant Haematologist and WM lead at University College London Hospitals

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