CLL Coverage from Every Angle

SEQUOIA Update on Zanubrutinib Versus Bendamustine Plus Rituximab in CLL

By: Lauren Harrison, MS
Posted: Friday, January 7, 2022

The Bruton’s tyrosine kinase inhibitor zanubrutinib demonstrated statistically significant improvement in progression-free survival in patients with chronic lymphocytic leukemia or small lymphocytic leukemia (CLL/SLL), according to the interim results from the phase III SEQUOIA trial. Constantine S. Tam, MBBS, MD, of the Peter MacCallum Cancer Centre in Melbourne, Australia, and colleagues, who presented these findings at the 2021 American Society of Hematology (ASH) Annual Meeting & Exposition (Abstract 396), believe their data support “the potential utility” of this agent in the front-line management of treatment-naive CLL/SLL.

This study enrolled 479 patients with CLL/SLL who had never received treatment. Patients were randomly assigned to receive either 160 mg of zanubrutinib twice a day or 90 mg/m2 of bendamustine with 375 mg/m2 of rituximab in cycle 1, followed by 500 mg/m2 of rituximab in cycles 2 through 6. There were 241 patients in the zanubrutinib group and 238 in the bendamustine/rituximab group.

After a median follow-up of 26.2 months, progression-free survival as assessed by an independent review committee was prolonged in the zanubrutinib group (hazard ratio = 0.42, P < .0001). These benefits were seen in several subgroups, including those stratified by age, Binet stage, bulky disease, and del(11q) status. Patients with unmutated IGHV also had survival benefits with zanubrutinib compared with the combination therapy (hazard ratio = 0.24, P < .0001); however, those with IGHV did not (hazard ratio = 0.67, P = .0929). The objective response rate was 94.6% with the single therapy and 85.3% with the dual therapy. The complete response rate was 6.6% with zanubrutinib and 15.1% with bendamustine and rituximab.

The most common grade 3 or higher adverse events seen with zanubrutinib versus bendamustine/rituximab were neutropenia (9.2% vs. 41.4%, respectively), hypertension (6.3% vs. 4.8%), thrombocytopenia (1.7% vs. 7.0%), decreased neutrophil count (2.1% vs. 10.6%), and febrile neutropenia (0.8% vs. 7.5%).

Disclosure: For a full list of authors’ disclosures, visit

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