FDA Approves Zanubrutinib for Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma

On January 19, 2023, the Food and Drug Administration (FDA) approved zanubrutinib for chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL). This approval was based on the SEQUOIA and ALPINE trials, respectively.

The efficacy of zanubrutinib in patients with treatment-naïve CLL/SLL was evaluated in SEQUOIA. In the randomized cohort, a total of 479 patients without 17p deletion were randomized 1:1 to receive either zanubrutinib until disease progression or unacceptable toxicity, or bendamustine plus rituximab for 6 cycles. The main efficacy outcome measure was progression-free survival (PFS) as determined by an independent review committee (IRC).

The median PFS was not reached (95% CI, not estimable [NE] to NE) in the zanubrutinib arm and was 33.7 months (95% CI, 28.1 to NE) in the bendamustine plus rituximab arm (HR = 0.42; 95% CI, 0.28 to 0.63; P = < .0001). Estimated median follow-up for PFS was 25.0 months. In a separate non-randomized cohort of SEQUOIA, zanubrutinib was evaluated in 110 patients with previously untreated CLL/SLL with 17p deletion. Overall response rate (ORR) per IRC was 88% (95% CI, 81 to 94). The median duration of response (DOR) was not reached after a median follow-up of 25.1 months.

The efficacy of zanubrutinib in patients with relapsed or refractory (R/R) CLL/SLL was evaluated in the ALPINE trial. A total of 652 patients were randomized 1:1 to receive either zanubrutinib or ibrutinib. The median number of prior lines of therapy was 1. The main efficacy outcome measures at the time of response analysis were ORR and DOR as determined by an IRC. The ORR was 80% (95% CI, 76 to 85) in the zanubrutinib arm and 73% (95% CI, 68 to 78) in the ibrutinib arm (response rate ratio 1.10; 95% CI, 1.01 to 1.20; P = .0264). The median DOR 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 decreased neutrophil count (42%), upper respiratory tract infection (39%), decreased platelet count (34%), hemorrhage (30%), and musculoskeletal pain (30%). Second primary malignancies, including non-skin carcinomas, developed in 13% of patients. Atrial fibrillation or flutter were reported in 3.7% of patients, and grade ≥3 arrhythmias in 0.2% of patients.

Source:

FDA approves zanubrutinib for chronic lymphocytic leukemia or small lymphocytic lymphoma. Press Release. The US Food and Drug Administration. Published online January 19, 2023. Accessed January 20, 2023. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-zanubrutinib-chronic-lymphocytic-leukemia-or-small-lymphocytic-lymphoma