Blood Cancer Drugs Show Promise in Treating Severe COVID-19
Drugs used to treat types of leukemia and lymphoma are showing promise for controlling “cytokine storms” in patients with severe COVID-19. Find out which agents have been investigated and how effective they were in helping patients be able to breath on their own.
BETHESDA, MD – Bruton tyrosine kinase (BTK) inhibitors used to treat blood cancers are showing promise in helping to control “cytokine storms,” the exaggerated immune response associated with COVID-19 in severely ill patients.
An article in Science Immunology describes how acalabrutinib, a selective BTK inhibitor, was administered off-label to 19 patients hospitalized with severe COVID-19. National Cancer Institute-led researchers note that 11 of them were on supplemental oxygen and eight on mechanical ventilation, with all but one of the 19 having increasing oxygen requirements at baseline.
Results indicate that, over a 10-14-day treatment course, acalabrutinib improved oxygenation in a majority of patients, often within one-to-three days, without discernable toxicity.
Background information in the articles points out that patients with severe COVID-19 have a hyperinflammatory immune response suggestive of macrophage activation, adding that BTK regulates macrophage signaling and activation.
In the patients receiving acalabrutinib, measures of inflammation – C-reactive protein and IL-6 – normalized quickly in most patients. So did lymphopenia, as oxygenation improved. By the end of acalabrutinib treatment, eight of 11, 72.7%, patients in the supplemental oxygen cohort had been discharged on room air, and half of the eight patients in the mechanical ventilation cohort had been successfully extubated, with two of them discharged on room air.
“Ex vivo analysis revealed significantly elevated BTK activity, as evidenced by autophosphorylation, and increased IL-6 production in blood monocytes from patients with severe COVID-19 compared with blood monocytes from healthy volunteers,” the authors write. “These results suggest that targeting excessive host inflammation with a BTK inhibitor is a therapeutic strategy in severe COVID-19 and has led to a confirmatory international prospective randomized controlled clinical trial.”
Use of BTK inhibitors to help treat severe COVID-19 got further support from research at the Dana Farber Cancer Institute. A letter in the journal Blood discussed the potential for ibrutinib, which is used to treat indolent B-cell malignancies and chronic graft-versus-host disease, to moderate pulmonary inflammatory cytokines, lung injury, and death. Those effects also were demonstrated in a highly relevant lethal flu animal model, according to the study team.
Dana Farber researchers describe how they care for 600 to 800 Waldenstrom macroglobulinemia (WM) patients each year, and about 300 of them are on a BTK inhibitor. Recently, six of the WM patients receiving ibrutinib were diagnosed with COVID-19; five were on the recommended treatment dose of 420 mg/d, while the sixth patient was on a reduced dose of 140 mg/d because of arthralgias. For all patients, the median time on ibrutinib was 52 months.
The authors point out, the five patients on ibrutinib, 420 mg/d, did not experience dyspnea and did not require hospitalization. “Their course was marked by steady improvement, and resolution or near resolution of COVID-19–related symptoms during the follow-up period,” according to the report.
The patient on reduced dose ibrutinib experienced progressive dyspnea and hypoxia prompting hospitalization, however.
Noting the lack of hypoxia in the other COVID-19–infected WM patients on full-dose ibrutinib, clinicians increased ibrutinib for the severely ill patient to 420 mg/d on days 11 and 12. They report a rapid improvement in oxygenation, adding that, by day 14, oxygen saturation was 95% on room air, and he was discharged home off of supplemental oxygen and prescribed 420 mg/d of ibrutinib.
“Therefore, ibrutinib, and possibly other BTK inhibitors, may 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,” the researchers wrote. “These findings should be considered 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.”
The authors call for validating their findings in other patient populations who are taking BTK inhibitors, including chronic lymphocytic leukemia patients.