BTK Inhibitors in Cancer Patients with COVID-19: "The Winner Will be the One Who Controls That Chaos" (Napoleon Bonaparte)

Clin Cancer Res. 2020 Jul 15;26(14):3514-3516. doi: 10.1158/1078-0432.CCR-20-1427. Epub 2020 Apr 28.

Abstract

As the SARS-CoV-2 (COVID-19) pandemic spreads and the number of Bruton's tyrosine kinase inhibitor (BTKi)-treated COVID-19-affected patients grows, we must consider the pros and cons of BTKi discontinuation for our patients. In favor of BTKi continuation, BTK plays an active role in macrophage polarization. By modulating key transcription factors, BTK may regulate macrophage polarization downstream of classic M1 and M2 polarizing stimuli and mitigate the hyperinflammatory state associated with COVID-19. In favor of BTKi discontinuation, we note a potentially increased risk of secondary infections and impaired humoral immunity. We hypothesize that the potential benefit of blunting a hyperinflammatory response to SARS-CoV-2 through attenuation of M1 polarization outweighs the potential risk of impaired humoral immunity, not to mention the risk of rapid progression of B-cell malignancy following BTKi interruption. On the basis of this, we suggest continuing BTKi in patients with COVID-19.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenine / analogs & derivatives
  • Agammaglobulinaemia Tyrosine Kinase / antagonists & inhibitors
  • Anti-Inflammatory Agents / adverse effects
  • Anti-Inflammatory Agents / therapeutic use*
  • Antineoplastic Agents / adverse effects
  • Antineoplastic Agents / therapeutic use
  • Benzamides / therapeutic use
  • Betacoronavirus / drug effects
  • COVID-19
  • Coronavirus Infections / drug therapy*
  • Coronavirus Infections / pathology
  • Humans
  • Inflammation / prevention & control
  • Leukemia, Lymphocytic, Chronic, B-Cell / drug therapy*
  • Lymphoma, B-Cell / drug therapy*
  • Macrophages / immunology
  • Pandemics
  • Piperidines / therapeutic use
  • Pneumonia, Viral / drug therapy*
  • Pneumonia, Viral / pathology
  • Protein Kinase Inhibitors / adverse effects
  • Protein Kinase Inhibitors / therapeutic use*
  • Pyrazines / therapeutic use
  • Pyrazoles / therapeutic use
  • Pyrimidines / therapeutic use
  • SARS-CoV-2

Substances

  • Anti-Inflammatory Agents
  • Antineoplastic Agents
  • Benzamides
  • Piperidines
  • Protein Kinase Inhibitors
  • Pyrazines
  • Pyrazoles
  • Pyrimidines
  • ibrutinib
  • zanubrutinib
  • Agammaglobulinaemia Tyrosine Kinase
  • acalabrutinib
  • Adenine