The U.S. Food and Drug Administration (FDA) has approved zanubrutinib (Brukinsa) to treat adults with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL).

CLL is a rare blood cancer resulting in a build-up of lymphocytes in bone marrow, lymph nodes, and blood. The disease is considered treatable, but relapse is very common.

Zanubrutinib is a Bruton’s tyrosine kinase (BTK) inhibitor. The drug has previously been approved to treat patients with mantle cell lymphoma, Waldenstrom’s macroglobulinemia, and marginal zone lymphoma.

The approval was largely based on data from two phase 3 clinical trials – the ALPINE study (relapse/refractory patients) and the SEQUOIA study (newly diagnosed patients).

In the ALPINE study, patients with relapsed or refractory CLL or SLL were randomized to receive zanubrutinibor ibrutinib. At a median follow-up of 29.6 months, zanubrutinib was superior to ibrutinib regarding progression-free survival among 652 patients. At 24 months, progression-free survival was 78.4% in the zanubrutinib group and 65.9% in the ibrutinib group. These results were recently published in the New England Journal of Medicine.

In the open-label SEQUOIA study, three cohorts were studied. All patients with CLL or SLL were treatment-naïve. In cohort 1, patients (n=479)  not harboring del(17p) were randomized to receive zanubrutinib or bendamustine + rituximab. In cohort 2, patients with del(17p) (n=110) received zanubrutinib monotherapy. In cohort 3, patients with del(17p) or pathogenic TP53 variant (ongoing study) are receiving  zanubrutinib plus venetoclax.

Data from the first cohort was published in Lancet Oncology and  showed zanubrutinib was superior to bendamustine + rituximab regarding progressive-free survival in patients without del(17p).

the most common adverse reactions (≥30%), observed with zanubrutinib treatment were decreased neutrophil count (42%), upper respiratory tract infection (39%), decreased platelet count (34%), hemorrhage (30%), and musculoskeletal pain (30%).

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