Dr. Constantine Tam on the Role of Zanubrutinib in Frontline CLL Treatment

During the 2025 ASCO Annual Meeting, Dr. Constantine Tam, MD, MBBS, hematologist at Alfred Hospital and Professor of Hematology at Monash University in Melbourne, Australia, discusses the long-term outcomes from arm C of the SEQUOIA study—an important registration trial evaluating zanubrutinib, a next-generation BTK inhibitor, in chronic lymphocytic leukemia (CLL). The conversation focuses on updated results being presented at ASCO, specifically in patients with high-risk 17p deletion.

Dr. Tam walks through the study’s context, which compared frontline zanubrutinib to bendamustine and rituximab, demonstrating the superiority of zanubrutinib in both efficacy and safety. Importantly, for the subgroup of patients with 17p deletion—who were not randomized due to ethical concerns surrounding chemotherapy—zanubrutinib showed remarkable durability. After five years, patients showed a median progression-free survival not previously seen in this high-risk population.

The interview highlights a 97% overall response rate, which Dr. Tam says is both reassuring and expected for BTK inhibitors. While the complete remission (CR) rate was 18%, he explains that CR is not essential for long-term success with these agents. Most patients begin in partial remission, which matures over time while maintaining a high quality of life.

Dr. Tam also addresses the practicalities of managing older, comorbid patients—the real-world population enrolled in SEQUOIA. The long-term safety profile remains favorable, with atrial fibrillation occurring in just 8% and hypertension in fewer than 20% of patients over five years, and no increased infection risk.

The findings affirm zanubrutinib as a highly effective and tolerable option for older CLL patients with 17p deletion, and Dr. Tam reinforces its place as the go-to therapy in this challenging group.