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Ibrutinib May Improve Pulmonary Outcomes in Certain COVID-19 Cases

Findings from a small clinical trial of patients with Waldenstrom’s macroglobulinemia (WM) suggest that ibrutinib may protect against lung injury and improve pulmonary function in hypoxic patients with COVID-19 (https://doi.org/10.1182/blood.2020006288).

“The potential for ibrutinib to abrogate pulmonary inflammatory cytokines, lung injury and death was previously demonstrated in a highly relevant, lethal flu animal model. We therefore sought to clarify the impact of ibrutinib in COVID-19 patients,” explained Steven P. Treon, MD, PhD, Dana Farber Cancer Institute and Brigham and Women’s Hospital, Boston, Massachusetts, and colleagues.

With between 600 and 800 patients with WM under their care each year—approximately 300 of whom receive BTK inhibitor therapy—Dr Treon et al identified 6 patients (median age, 66 years) receiving ibrutinib for WM who had COVID-19.

Treatment lasted for a median of 52 months for all patients, including 5 were receiving 420 mg daily (the recommended dose) and 1 receiving 140 mg daily because of arthralgias. The median duration that patients had COVID-19–related symptoms before diagnostic testing was 5 days, and the median time since COVID-19 diagnosis was 22 days.

Although all 6 patients had fever and cough, only the patient given ibrutinib 140 mg daily had progressive dyspnea and hypoxia that required hospitalization; the 5 recipients of ibrutinib 420 mg daily had no dyspnea and did not need to be hospitalized. According to Dr Treon and co-investigators, there was a steady improvement observed in these 5 patients during the follow-up period, with resolution or near-resolution of COVID-19–related symptoms.

After a CT scan of the chest showed bilateral ground glass opacities and a pleural effusion in the sixth patient receiving reduced-dose ibrutinib, treatment with ibrutinib was held and hydroxychloroquine (HCQ) and azithromycin were administered for 3 and 5 days, respectively.

On the fifth day, ibrutinib 140 mg daily was restarted and co-administered with tocilizumab 400 mg. Because this patient had worsening hypoxia whereas recipients of ibrutinib 420 mg had no hypoxia, Dr Treon et al increased the ibrutinib dose to 420 mg daily on days 11 and 12.

The patient’s oxygen levels gradually improved, and by day 14 they were discharged with continued receipt of ibrutinib 420 mg daily.

The investigators report that, 1 week later, the patient is doing well without fever, cough, or dyspnea at rest and continues to receive ibrutinib 420 mg daily.

“Ibrutinib and possibly other BTK-inhibitors may therefore provide protection against lung injury, and even improve pulmonary function in hypoxic patients with COVID-19 as we observed in this series of WM patients on ibrutinib,” Dr Treon and colleagues posited.

“These findings should be considered as hypothesis generating and preliminary in nature. Patients on ibrutinib, and possibly other BTK-inhibitors may well benefit with continuation of their therapy despite the diagnosis of COVID-19,” they concluded.—Hina M. Porcelli

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