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Jeremy S. Abramson, MD, MMSc
Jeremy S. Abramson, MD, MMSc
Posted: Wednesday, March 2, 2022
According to Constantine S. Tam, MD, of Peter MacCallum Cancer Centre, Melbourne, and colleagues, in the phase I/II AU-003 study, the next-generation Bruton’s tyrosine kinase inhibitor zanubrutinib seemed to be safe and active in patients with treatment-naive or relapsed or refractory chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL). The updated safety and efficacy data, which were published in the British Journal of Haematology, further supported these findings.
Patients were administered zanubrutinib at a dose level of 160 mg twice daily (n = 81), 320 mg once daily (n = 40), or 160 mg once daily (n = 2). Follow-up data were provided for a median of 47.2 months.
Treatment discontinuations due to adverse events or disease progression were uncommon, according to the investigators. The overall response and complete response rates were 95.9% (treatment-naive: 100%; relapsed or refractory: 95%) and 18.7%, respectively. An ongoing response was reported in 85.7% of patients at 3 years. In patients with del(17p) and TP53 mutation, the overall response rate was 87.5%; the complete response rate was 16.7%. The estimated 2- and 3-year progression-free survival rates were 90% (treatment-naive: 90%; relapsed or refractory: 91%) and 83% (treatment-naive: 81%; relapsed or refractory: 83%), respectively.
Neutropenia (15.4%), pneumonia (9.8%), hypertension (8.9%), and anemia (6.5%) were the most frequently reported adverse events of grade 3 or higher. The annual incidence rates of atrial fibrillation, major hemorrhage, neutropenia of grade 3 or higher, and infection of grade 3 or higher seemed to decrease over time. At a median follow-up of approximately 4 years, responses remained clinically meaningful and durable, according to the investigators.
“The combination of sustained efficacy with acceptable tolerability with prolonged single-agent zanubrutinib in patients with CLL or SLL suggest long-term use is feasible, even for those with unfavorable disease characteristics,” the investigators concluded.
Disclosure: For full disclosures of the study authors, visit onlinelibrary.wiley.com.
British Journal of Haematology
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