Understanding the Role of Zanubrutinib for the Treatment of CLL

Current frontline treatment options for patients with chronic lymphocytic leukemia (CLL) have grown over the past year, specifically with the approval of 2 Bruton’s tyrosine kinase (BTK) inhibitors. Notably, in January 2023, the FDA approved zanubrutinib (Brukinsa) for adult patients with CLL or small lymphocytic leukemia (SLL) based on data from 2 phase 3 randomized studies: ALPINE (NCT03734016) and SEQUOIA study (NCT03336333).

ALPINE Trial

In the phase 3 ALPINE trial, investigators assessed treatment with zanubrutinib vs ibrutinib (Imbruvica) in patients with relapsed/refractory CLL.

Of the 415 evaluated patients included in the study, the overall response rate (ORR) among those treated with zanubrutinib was 80% (95% CI, 76-85) vs 73% (95% CI, 68-78) in the ibrutinib arm (HR, 1.10; 95% CI, 1.01-1.20; P =.0264). After a median follow-up of 14.1 months, the median duration of response (DOR) was not reached in either arm.

SEQUOIA Trial

In the SEQUOIA trial, zanubrutinib was compared with bendamustine and rituximab (Rituxan) in treatment of treatment-naïve patients with CLL. Here, the median progression-free survival (PFS) was not reached in the zanubrutinib arm vs 33.7 months (95% CI, 28.1-NE) in the bendamustine and rituximab arm (HR, 0.42; 95% CI, 0.28-0.63; P ≤ .0001). The estimated median follow-up was 25.0 months.

A total of 110 patients were given zanubrutinib within a separate non-randomized cohort of the study. Of these patients, all had previously untreated CLL/SLL with 17p deletion. In this cohort, the ORR was 88% (95% CI, 81-94), and the median DOR was not reached after a median follow-up of 25.1 months.

Safety

The most frequent adverse events seen in at least 30% of patients who received zanubrutinib included neutrophil count decrease (42%), upper respiratory tract infection (39%), platelet count decrease (34%), hemorrhage (30%), and musculoskeletal pain (30%). Zanubrutinib was generally well-tolerated among patients with CLL, low rates of atrial fibrillation were strong efficacy seen compared [with] ibrutinib and chemoimmunotherapy.