Combined analysis of the impact of second-generation BTK inhibitors on patient outcomes

Abstract

BTK inhibitors (BTKi) are highly effective in B-cell malignancies. Acalabrutinib and zanubrutinib have exhibited favorable safety profiles when compared with ibrutinib. We identified all published/presented randomized trials comparing a second-generation BTKi with ibrutinib and reconstructed individual patient-level, censored time-to-event data for adverse events to evaluate the impact of second-generation BTKi on safety outcomes including atrial fibrillation/flutter [AF], hypertension, bleeding, diarrhea, and infection. 1386 pts from ELEVATE-RR (n = 533), ALPINE (n = 652), and ASPEN (n = 201) trials were included in the analyses. Acalabrutinib or zanubrutinib were associated with significant reductions in cumulative event rates of AF (HR 0.28, 95% CI 0.18–0.42, p < 0.001), bleeding (HR 0.65, 95% CI 0.52–0.81, p < 0.001), diarrhea (HR 0.61, 95% CI 0.47–0.78, p < 0.001), hypertension (HR 0.40, 95% CI 0.27–0.61, p < 0.001), and infections (HR 0.83, 95% CI 0.70-0.98, p = 0.032). In summary, zanubrutinib and acalabrutinib have a favorable safety profile among pts with r/r B-cell malignancies. These data support use of acalabrutinib or zanubrutinib as preferred BTK inhibitors for approved indications.

Keywords:

• BTK inhibitor
• zanubrutinib
• acalabrutinib
• ibrutinib
• chronic lymphocytic leukemia
• small lymphocytic lymphoma

Acknowledgements

The authors are grateful to the patients for participating in the included trials.

Disclosure statement

Robert Redd and Josie Ford report no conflict of interest. Matthew Lei reports consulting fees from BTG Therapeutics, AstraZeneca, Genentech, Genmab, and TScan Therapeutics. Jeremy S. Abramson reports consulting fees from Beigene, Bluebird Bio, Kymera, Genentech, Incyte, Kite Pharma, Epizyme, Genmab, Bristol Myers Squibb, Ono Pharma, Mustang Bio, Century Therapeutics, AstraZeneca, AbbVie, Lilly, Takeda, Caribou Bioscences, Interius, and Cellectar, honoraria from Genmab, Bristol Myers Squibb, AstraZeneca, MorphoSys, Regeneron, Janssen, Incyte, and Abbvie, and research funding paid to institution from Bristol Myers Squibb, Seattle Genetics, Merck, Cellectis, and Mustang Bio. Jacob D. Soumerai reports consulting fees from Abbvie, AstraZeneca, Beigene, Bristol Myers Squibb, Roche, Seattle Genetics, and TG Therapeutics, and research funding paid to institution from Adaptive Biotechnologies, Beigene, BostonGene, Genentech/Roche, GlaxoSmithKline, Moderna, Takeda, and TG Therapeutics.

Additional information

Funding

Jacob D. Soumerai MD is supported by the National Cancer Institute of the National Institutes of Health under award number [K08CA270202].