Fewer Infections, Partial Restoration of Humoral Immunity Linked With Ibrutinib Use

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Ibrutinib is a well-tolerated therapy in patients with chronic lymphocytic leukemia that may increase IgA levels and decrease infection rate.
Ibrutinib is a well-tolerated therapy in patients with chronic lymphocytic leukemia that may increase IgA levels and decrease infection rate.

Ibrutinib is a well-tolerated therapy in patients with chronic lymphocytic leukemia (CLL) that may increase IgA levels and conversely decrease infection rate, but extended studies are required to investigate the safety of long-term Bruton's tyrosine kinase (BTK) inhibition, according to an article published online ahead of print in Blood.1

CLL has been known to cause immunoglobulin deficiencies, which may result in infection-related morbidity and mortality. Ibrutinib is a novel therapy that binds BTK to inhibit B-cell receptor signaling.

A phase 2 trial investigated ibrutinib's effect on humoral immunity and infection rate in patients with treatment-naïve or relapsed/refractory CLL.

Eighty-six patients received ibrutinib 420 mg daily for 2 years, and analyses on serum immuoglobulins, B-cells, and infection rates were performed.

Stable levels of IgG were observed within the first 6 months but declined at 12 and 24 months (P<0.0001), while IgA levels increased at both time points (P<0.0001).

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At 12 months, the percentage of normal B-cells was superior in treatment-naïve patients (78% vs. 29%, P<0.0001), but at 24 months this difference was no longer detectable.

Infections were frequent in the first 6 months of treatment and may have been due to the disease itself. Infections of any grade occurred more in previously treated patients, and patients with a 50% or greater increase in IgA had a lower infection rate (P=0.3).

Reference

  1. Sun C, Tian X, Lee YS, et al. Partial reconstitution of humoral immunity and fewer infections in patients with chronic lymphocytic leukemia treated with ibrutinib. Blood. 2015 Sep 3. doi: 10.1182/blood-2015-04-639203

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