Patients with chronic lymphocytic leukemia (CLL) assigned to treatment with a BTK inhibitor experienced an initial reduction in certain innate immune cell functions, but most of these processes were recovered in the long term, according to the results of a recent paper.

BTK inhibitors act on B cells and a wide variety of other tissues and cells, including immunity cells. Therefore, alteration in the function of BTK kinase could lead to immune impairment. 

Recently, researchers analyzed in vivo neutrophils oxidative burst, neutrophils granules release, and cytokine production in patients with relapsed or refractory CLL who had been treated with the BTK inhibitor ibrutinib. 

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The study showed that even during the first 48 hours of treatment, there was a dramatic reduction of neutrophils oxidative burst, Fc gamma receptor-mediated degranulation, and IL-8 plasma levels. No effect was seen on surface expression of CD11b nor cytokine and proteinases release not mediated by Fc gamma receptor engagement. 

At 3 weeks, oxidative burst was still impaired, “indicating a persistent inhibitory effect during the early phases of treatment,” but degranulation and IL-8 levels were restored, suggesting a transient inhibition.

In a group of 6 patients who survived more than 3 years, all processes triggered by Fc gamma receptors were completely recovered except for release of neutrophil elastase and IL-8. 

“These results suggest that in the long-term period the effects of BTK pharmacologic inhibition on FcγRs-mediated processes were mostly reverted,” the researchers wrote. 

“Taken together our data suggest that during the first phases of treatment, the inhibition of BTK suppresses FcγRs-mediated neutrophils functions, potentially in a clinically relevant way. This neutrophils impairment might represent an additional infectious risk in CLL patients receiving ibrutinib beyond the impairment of B-cell responses.”


Prezzo A, Cavaliere FM, Bilotta C, et al. Ibrutinib-based therapy impaired neutrophils microbicidal activity in patients with chronic lymphocytic leukemia during the early phases of treatment. Leuk Res. 2019;87:106233.