Feb 2023: Zanubrutinib (Brukinsa, BeiGene USA, Inc.) is approved by FDA for chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL).
SEQUOIA was used to assess effectiveness in CLL/SLL patients who had not received treatment (NCT03336333). A total of 479 patients were randomised 1:1 to receive either zanubrutinib until disease progression or unacceptable toxicity or bendamustine plus rituximab (BR) for 6 cycles in the randomised cohort that included patients without 17p deletion. Progression-free survival (PFS) was the primary efficacy outcome metric, as established by a separate review committee (IRC). In the zanubrutinib arm, the median PFS was not achieved (95% CI: NE, NE), but in the BR arm, it was 33.7 months (95% CI: 28.1, NE) (HR= 0.42, 95% CI: 0.28, 0.63; p=0.0001). For PFS, the estimated median follow-up was 25.0 months. Zanubrutinib was assessed in 110 patients with previously untreated CLL/SLL with a 17p deletion in a different non-randomized cohort of SEQUOIA. IRC reported an overall response rate (ORR) of 88% (95% CI: 81, 94). After a median follow-up of 25.1 months, the median duration of response (DOR) had not yet been attained.
ALPINE assessed the effectiveness in patients with relapsed or refractory CLL/SLL (NCT03734016). 652 participants in total were randomly assigned to either zanubrutinib or ibrutinib. 1 was the median number of previous lines of treatment (range 1-8). ORR and DOR were the primary efficacy outcome measures at this point in the response analysis, according to an IRC. The ORR for the zanubrutinib arm was 80% (95% CI: 76, 85) and for the ibrutinib arm was 73% (95% CI: 68, 78) (response rate ratio: 1.10, 95% CI: 1.01, 1.20; p=0.0264). After a median follow-up of 14.1 months, neither arm had reached the median DOR.
The most frequent side effects of zanubrutinib (30%) included bleeding (42%), lower respiratory tract infection (39%), decreased platelet count (34%), decreased neutrophil count (42%), and musculoskeletal pain (30%). In 13% of individuals, secondary primary malignancies, such as non-skin carcinomas, occurred. 3.7% of patients had atrial fibrillation or flutter, while 0.2% of patients had ventricular arrhythmias grade 3 or above.
Until the disease progresses or there is intolerable toxicity, the recommended zanubrutinib dosage is 160 mg taken orally twice day or 320 mg taken orally once daily.
