Ibrutinib for chronic lymphocytic leukemia in the setting of respiratory failure from severe COVID-19 infection: Case report and literature review

Ibrutinib, a known Burton's tyrosine kinase (BTK) and interleukin-2 inducible T-cell kinase (ITK) inhibitor, is used for the treatment of B-cell disorders (chronic lymphocytic leukemia [CLL] and various other lymphomas) and chronic graft versus host disease following allogeneic hematopoietic cell transplantation. Because it is considered an immunosuppressant, continuation of ibrutinib is often debated when patients have an active infection, and this becomes an especially difficult decision in the setting of coronavirus disease 2019 (COVID-19). Here, we describe a patient with CLL who was on ibrutinib then developed severe COVID-19 infection requiring mechanical ventilation. We elected to continue ibrutinib the same day he was intubated, reasoning that BTK inhibition in myeloid immune cells has been shown to reduce or even reverse influenza-mediated acute lung injury and that ITK inhibition in T cells has correlated with reduction in viral replication, and therefore may have an advantage in this setting. Ibrutinib also has been shown to block Src family kinases, which potentially could result in reduction of viral entry and the inflammatory cytokine response in the lungs. The patient was extubated after 9 days with a complex hospital course and eventually discharged on room air. The only way to rationally inform these decisions and explore similar potentially promising leads in this pandemic is to conduct carefully done clinical trials.

Keywords: BTK inhibitor; COVID‐19; Ibrutinib; acute respiratory distress syndrome; chronic lymphocytic leukemia.