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.