Long-term follow-up of patients with CLL treated with the selective Bruton's tyrosine kinase inhibitor ONO/GS-4059.

[First paragraph] The inhibitor of Bruton’s tyrosine kinase (BTK) ibrutinib has transformed the treatment of chronic lymphocytic leukemia (CLL); many patients with previously untreatable disease may now enter durable remissions.1,2 Nevertheless, the kinome of ibrutinib is broad, resulting in toxicities including bleeding, arthralgia, diarrhea, hypertension, and atrial fibrillation.3-6 Up to 20% of patients discontinue ibrutinib due to toxicity.7-9 More selective BTK inhibitors (BTKis) include ONO/GS-4059, acalabrutinib, and BGB-3111. Preliminary data indicate that these drugs have comparable activity to ibrutinib, but with reduced toxicities.10-12 However, long-term follow-up and response data have not yet been reported. We provide an updated, 3-year follow-up of treatment efficacy, safety, and laboratory correlates, including baseline mutational profiling of CLL patients in the phase 1 ONO/GS-4059 extension study.