Case Report: Ibrutinib Might Protect Against Acute Lung Injury in Patients With CLL, COVID-19

One of the most difficult decisions facing oncologists is whether to suspend immunosuppressive therapy due to the risk of coronavirus disease 2019 (COVID-19) infection. In a new case report in eJHaem, investigators outlined what happened when they continued a course of ibrutinib (Imbruvica) with a patient who had chronic lymphocytic leukemia (CLL).

Ibrutinib is a Bruton’s tyrosine kinase (BTK) inhibitor and an interleukin-2 inducible T-cell kinase (ITK) inhibitor. The patient had developed a severe case of COVID-19, but was able to successfully continue taking ibrutinib, and the authors suggest the drug may have helped protect the patient.

The subject, a 77-year-old male, is a patient at the Robert H. Lurie Comprehensive Cancer Center, part of the Northwestern University Feinberg School of Medicine. His CLL, 13q del, was diagnosed in 2005. He was started on ibrutinib at a dosage of 420 mg/day in March 2016. He had been stable for 4 years.

In March 2020, he visited an urgent care clinic, reporting a sore throat, fevers up to 101°F,and a slight dry cough; he had recently been on an overseas trip. He tested positive for strep throat, so the clinic did not send his COVID-19 test for analysis.

Six days later, he arrived in the emergency department with progressive symptoms and oxygen saturation of 89% on a 2L nasal cannula. He was given a COVID-19 test, and it came back positive. He was sent to the intensive care unit.

Initially, his doctors stopped ibrutinib. On the second day of his admission, he was intubated and put on oxygen ventilation, as the doctors feared his case might be more severe than average due to his age and underlying conditions. His physicians conducted an interdisciplinary discussion to consider what to do about ibrutinib.

“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 (ALI) and that ITK inhibition in T cells has correlated with reduction in viral replication, and therefore may have an advantage in this setting,” wrote corresponding author Leo I. Gordon, MD, and colleagues.

They also noted that ibrutinib has been shown to block Src family kinases, which could reduce viral entry and the inflammatory cytokine response in the lungs. So, they started the patient on a higher dose of 560 mg.

On the 12th day of his admission, the patient was extubated to a high-flow nasal cannula. Day 14 saw him transferred to the COVID-19 unit on a 2L nasal cannula. However, the next day, the patient had recurrent acute hypoxemic respiratory failure with apparent ventilator-associated pneumonia.

He was extubated after 2 days, weaned off oxygen 3 days later, and eventually discharged to acute rehabilitation 28 days after admission. At that point, his dose was returned to 420 mg. After 2 weeks of rehab, he was sent home.

The authors concluded that it is possible ibrutinib played a protective role against ALI, but they said it’s difficult to know for sure, since he was also on other medications, such as tocilizumab (Actemra).

“Although logically BTK inhibitors should have efficacy in preventing or treating ALI in COVID-19, further studies in animal models as well as clinical trials are required to define the optimal role of ibrutinib in patients with life-threatening viral infections,” they said.

Reference

Lin AY, Cuttica MJ, Ison MG, Gordon LI.Ibrutinib for chronic lymphocytic leukemia in the setting of respiratory failure from severe COVID‐19 infection: case report and literature review. eJHaem. 2020;1-5. doi:10.1002/jha2.98