FDA approves zanubrutinib for chronic lymphocytic leukemia or small lymphocytic lymphoma

Regulatory approval: On January 19, 2023, the FDA approved zanubrutinib (Brukinsa; BeiGene USA, Inc.) for chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL). The approval was supported by efficacy results from the SEQUOIA trial in treatment-naïve CLL/SLL and the ALPINE trial in relapsed/refractory CLL/SLL, with key outcomes including progression-free survival and response rates as assessed by independent review.

FDA approval: zanubrutinib for CLL/SLL (Jan 19, 2023)

Type: Regulatory approval
Agency/date: FDA, 2023-01-19
Indication: Chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL)

The FDA approved zanubrutinib (Brukinsa; BeiGene USA, Inc.) for CLL/SLL.

Efficacy (treatment-naïve): SEQUOIA (NCT03336333)

  • In the randomized cohort without 17p deletion, 479 patients were randomized 1:1 to zanubrutinib (until progression/toxicity) vs bendamustine + rituximab (BR) for 6 cycles.
  • Primary endpoint: PFS by independent review committee (IRC).
  • Median PFS: not reached (95% CI: NE, NE) with zanubrutinib vs 33.7 months (95% CI: 28.1, NE) with BR; HR 0.42 (95% CI: 0.28, 0.63; p<0.0001). Median PFS follow-up: 25.0 months.
  • In a separate non-randomized cohort (n=110) with 17p deletion, ORR (IRC) was 88% (95% CI: 81, 94); median DOR not reached at median follow-up 25.1 months.

Efficacy (relapsed/refractory): ALPINE (NCT03734016)

  • 652 patients randomized 1:1 to zanubrutinib vs ibrutinib; median prior lines of therapy 1 (range 1–8).
  • At this response analysis: ORR (IRC) 80% (95% CI: 76, 85) vs 73% (95% CI: 68, 78); response rate ratio 1.10 (95% CI: 1.01, 1.20; p=0.0264). Median DOR not reached in either arm (median follow-up 14.1 months).

Safety (across trials): Common adverse reactions (≥30%) included 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) occurred in 13%; atrial fibrillation/flutter in 3.7%; grade ≥3 ventricular arrhythmias in 0.2%.

Recommended dosage: 160 mg orally twice daily or 320 mg orally once daily until progression or unacceptable toxicity.

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