Zanubrutinib in TN CLL: Expert Insights on Latest Data From SEQUOIA Arm C

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The SEQUOIA trial’s Arm C provided crucial data for high-risk patients with chronic lymphocytic leukemia (CLL) and deletion 17p (del 17p), a population historically excluded from chemotherapy-based regimens. This dedicated cohort study followed more than 100 patients with TP53 aberrations for 5 years, demonstrating the efficacy of zanubrutinib monotherapy in this challenging patient population. The trial design recognized that patients with del 17p require specialized treatment approaches due to their poor response to conventional therapies.

The 5-year progression-free survival rate of 72% in patients with del 17p who were treated with zanubrutinib represents a remarkable achievement in high-risk CLL management. This outcome closely paralleled the progression-free survival observed in TP53 wild-type patients, suggesting that continuous Bruton tyrosine kinase (BTK) inhibition can effectively overcome the traditionally poor prognosis associated with TP53 aberrations. These results establish zanubrutinib as a highly effective therapeutic option for the highest-risk patients with CLL.

The SEQUOIA Arm C findings fundamentally changed the treatment paradigm for patients with CLL and del 17p by demonstrating that continuous monotherapy with a second-generation BTK inhibitor can achieve durable disease control. These data provide oncologists with confidence when treating this historically challenging patient population and support using zanubrutinib as a frontline option for patients with TP53 aberrations, offering them long-term outcomes similar to those of lower-risk patients.