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Kinase Inhibitor Screening In Self-assembled Human Protein Microarrays
Published on: October 23, 2019
Pooled safety analysis of zanubrutinib monotherapy in Asian patients with B-cell malignancies
1Peking University Cancer Hospital & Institute (Beijing Cancer Hospital), Beijing, China.
Background:
In patients with B-cell malignancies, treatment with the first-generation Bruton tyrosine kinase (BTK) inhibitor ibrutinib can be limited by toxicities resulting from off-target binding. Zanubrutinib, a next-generation BTK inhibitor, was designed to maximize BTK occupancy and minimize off-target effects.
Materials And Methods:
A post hoc safety analysis was carried out with pooled data from Asian patients with B-cell malignancies who received zanubrutinib in eight clinical trials, including ALPINE, which compared zanubrutinib with ibrutinib. Rates and severity of treatment-emergent adverse events (TEAEs), overall exposure-adjusted incidence rates (EAIRs) of AEs of special interest (AESIs; defined as pooled terms), and EAIRs of AESIs over time were assessed.
Results:
The analyses included 406 Asian patients with a median treatment duration of 25.0 months; 38.7% of patients received treatment for ≥36 months. Upper respiratory tract infection (38.2%), pneumonia (26.4%), rash (21.2%), and diarrhea (16.5%) were the most common nonhematologic TEAEs. The most common nonhematologic grade ≥3 TEAEs were pneumonia (16.0%) and upper respiratory tract infection (6.9%). Serious TEAEs occurred in 43.8% of patients; pneumonia (14.5%) was the only event occurring in >10% of patients. TEAEs led to treatment discontinuation in 10.6% of patients and death in 4.9%, mostly due to infections. EAIRs for atrial fibrillation/flutter and hypertension were 0.02 and 0.56 persons per 100 person-months, respectively. In the comparative analysis, most EAIRs of AESIs were numerically lower in patients treated with zanubrutinib versus ibrutinib. Over time, EAIRs of AESIs remained relatively constant or decreased in the pooled Asian population and were similar to or lower than those with ibrutinib for up to 36 months.
Conclusions:
Zanubrutinib was well tolerated in Asian patients with B-cell malignancies. The safety profile in this population was consistent with that in previous global study populations. These findings suggest that long-term zanubrutinib treatment is an appropriate option for Asian patients with B-cell malignancies.
