Study Finds Zanubrutinib Active in CLL or Small Lymphocytic Lymphoma
Posted: Monday, January 27, 2020
The next-generation Bruton’s tyrosine kinase (BTK) inhibitor zanubrutinib demonstrated a high overall response rate against chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma, according to an update of a phase I/II study. Constantine S. Tam, MBBS, MD, of St Vincent’s Hospital, Peter MacCallum Cancer Centre, and the University of Melbourne, Australia, presented the research on behalf of colleagues at the 2019 American Society of Hematology (ASH) Annual Meeting & Exposition (Abstract 500).
“The overall response rate, complete response rate, and 2-year progression-free survival rates suggest this next-generation BTK inhibitor can achieve deep and durable responses,” the authors wrote.
The multicenter open-label study included 122 patients: 117 with CLL and 5 with small lymphocytic lymphoma. There were 120 evaluable patients who had enrolled at least 3 months before data cutoff. The doses of zanubrutinib ranged from 40 mg once daily to the final recommended phase II dose of 160 mg twice daily or 320 mg once daily until disease progression or unacceptable toxicity.
The median follow-up was 25 months. The overall response rate was 97%, and it was similar regardless of 17p deletion status. The complete response rate was 14%. Progression-free survival was 97% at 1 year and 89% at 2 years.
The primary endpoint was safety and tolerability. Grade 3 or higher adverse events occurred in 59% of patients. Serious adverse events occurred in 45% of patients, the most common being pneumonia (6%) and urinary tract infection (2%). Other noteworthy adverse events included bleeding (57%), secondary malignancies (20%), neutropenia (19%), hypertension (8%), thrombocytopenia (6%), atrial fibrillation (3%), and major hemorrhage (2%). A total of 4 patients (3%) discontinued treatment because of adverse events, and 13 (11%), because of disease progression.
Disclosure: The study authors’ disclosure information may be found at ash.confex.com.