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Study Reports Early-Stage Impairment of Neutrophil Activity With Ibrutinib for CLL

By: Kayci Reyer
Posted: Monday, December 2, 2019

According to findings published in Leukemia Research, the tyrosine kinase inhibitor ibrutinib may result in the impairment of the microbicidal activity of neutrophils early on in the treatment process in patients with chronic lymphocytic leukemia (CLL). As a result, immunity may be compromised during initial treatment.

“Our results are consistent with the observation that infectious complications appear to occur more frequently during the early part of treatment and decline over time during ibrutinib therapy,” concluded Isabella Quinti, MD, PhD, of Sapienza University, Rome, and colleagues. “Reasons for the decrease in infectious morbidity over time are potentially related to several factors, and improvement of neutrophilic activity can be one of them.”

The study included 10 patients with CLL and 12 disease-free patients who acted as a control group. Among the patients with CLL, one was treatment-naive; the others underwent a median number of three previous treatments, with a median time from last antileukemic treatment of 6 months. None had taken antibiotics within 3 months of beginning the study. Due to unrelated conditions, 8 of the 10 patients received low-dose steroid treatment in conjunction with ibrutinib for the first 4 to 6 weeks of therapy.

Ibrutinib was found to impair the oxidative burst typically generated by neutrophils, with a decrease evident within 48 hours of treatment initiation and through the first 3 weeks of treatment. Levels of interleukin-8 (IL-8) plasma, which supports neutrophil activity, was observed to experience a similar decrease in the first 2 days of therapy, although the levels improved to baseline after 3 weeks. In addition, ibrutinib was found to inhibit the degranulation of FcγRs-mediated serine proteases NE, MPO, and LF, an effect that persisted for 48 hours after the initial dose of ibrutinib but increased slightly 3 weeks later. Despite these interactions, ibrutinib was not found to alter the expression of CD11b, an indicator of activation of neutrophils.

Disclosure: The study authors reported no conflicts of interest.



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