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FDA Approves Zanubrutinib in Treatment of CLL or SLL

By: JNCCN 360 Staff
Posted: Monday, January 23, 2023

On January 19, 2023, the U.S. Food and Drug Administration (FDA) approved the kinase inhibitor zanubrutinib (Brukinsa) in the treatment of chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL).

Efficacy in patients with treatment-naive CLL or SLL was evaluated in the SEQUOIA trial (ClinicalTrials.gov identifier NCT03336333). In the randomized cohort of the SEQUOIA trial, including patients without 17p deletion, a total of 479 patients were randomly assigned 1:1 to receive either zanubrutinib until disease progression or unacceptable toxicity or bendamustine plus rituximab (BR) for six cycles. The median progression-free survival was not reached in the zanubrutinib arm and was 33.7 months in the BR arm (hazard ratio = 0.42, 95% confidence interval [CI] = 0.28–0.63; P < .0001). Estimated median follow-up for progression-free survival was 25.0 months.

In a separate nonrandomized cohort of SEQUOIA, zanubrutinib was evaluated in 110 patients with previously untreated CLL or SLL with 17p deletion. The overall response rate per independent review committee was 88% (95% CI = 81%–94%). The median duration of response was not reached after a median follow-up of 25.1 months.

Efficacy in patients with relapsed or refractory CLL or SLL was evaluated in the ALPINE trial (NCT03734016). A total of 652 patients were randomly assigned 1:1 to receive either zanubrutinib or ibrutinib. The median number of prior lines of therapy was one (range, 1–8). The overall response rate was 80% (95% CI = 76%–85%) with zanubrutinib and 73% (95% CI = 68%–78%) with ibrutinib (response rate ratio, 1.10, 95% CI = 1.01–1.20; P = .0264). The median duration of response was not reached in either arm, after a median follow-up of 14.1 months.

Across clinical trials of zanubrutinib, the most common adverse reactions (≥ 30%) were neutrophil count decreased (42%), upper respiratory tract infection (39%), platelet count decreased (34%), hemorrhage (30%), and musculoskeletal pain (30%). Second primary malignancies, including non-skin carcinomas, developed in 13% of patients. Atrial fibrillation or flutter was reported in 3.7% of patients, and grade 3 or higher ventricular arrhythmia was noted in 0.2% of patients.

The recommended zanubrutinib dosage is 160 mg taken orally twice daily or 320 mg taken orally once daily until disease progression or unacceptable toxicity.


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