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).
- 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