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FDA Approves Zanubrutinib for CLL/SLL

The FDA has permitted zanubrutinib (Brukinsa) for sufferers with persistent lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL).one

The really useful dose for the oral BTK inhibitor is 160 mg twice day by day or 320 mg as soon as day by day; the prescribing label comes with warnings for hemorrhage, infections, cytopenias, second main malignancies, and cardiac arrythmias.2

The regulatory determination is supported by efficacy information from the part 3 SEQUOIA (NCT03336333), and ALPINE (NCT03734016) trials. Throughout medical trials, the commonest antagonistic occasions (AEs) had been decreased neutrophil counts (42%), higher respiratory tract infections (39%), decreased platelet counts (34%) hemorrhage (30%), and musculoskeletal ache (30%) . Second main malignancies had been noticed in 13% of sufferers. Atrial fibrillation or flutter had been reported in 3.7% and 0.2% of sufferers skilled grade 3 or greater ventricular arrhythmias.

Zanubrutinib must be swallowed complete with water. It may be taken with or with out meals. Coadministration with sturdy or average CYP3A inducers must be averted and the dosage for zanubrutinib must be modified whether it is being taken with a CYP3A inhibitor.


In SEQUOIA, 479 treatment-naïve sufferers with CLL/SLL who didn’t have a 17p deletion had been randomly assigned 1:1 to obtain both zanubrutinib (n = 241) or bendamustine (Treanda) plus rituximab (Rituxan; BR) for six cycles ( n=238). The median progression-free survival (PFS) was not estimable (NE) with zanubrutinib (95% CI, NE-NE) vs 33.7 months with BR (95% CI, 28.1-NE). The estimated median follow-up time was 25.0 months, and the HR was 0.42 (95% CI, 0.28-0.63; P < .001). The general response fee (ORR) for sufferers receiving zanubrutinib was 93% (95% CI, 89%-96%) vs 85% (95% CI, 80%-90%) for these receiving BR. The entire response (CR) charges had been 7% vs 15%, respectively.2

Moreover, in a separate nonrandomized cohort wherein zanubrutinib was assessed in sufferers with a 17p deletion (n = 110), the ORR was 88% (95% CI, 81%-94%) and the median period of response was not reached after a median 25.1 months of follow-up. The CR fee was 6%.


Knowledge from the ALPINE trial additionally supported this approval, wherein zanubrutinib demonstrated superior efficacy and security when put next with ibrutinib (Imbruvica) in a inhabitants of sufferers with relapsed or refractory CLL/SLL. The ORR within the zanubrutinib arm (n = 327) was 80% (95% CI, 76%-85%) with 13 sufferers having a CR. Within the ibrutinib arm (n = 325) the ORR was 73% (95% CI, 68%-78%) with 8 sufferers experiencing a CR. The response fee ratio was 1.10 (95% CI, 1.01-1.20; P = .0264). Median period of response was not estimable in both arm and the median follow-up time was 14.1 months.1,2


For sufferers and not using a 17p deletion in SEQUOIA, 36% of sufferers had a severe AE, the commonest of which (≥ 5%) had been COVID-19, pneumonia, and secondary main malignancy. Everlasting discontinuation and doe discount had been noticed in 8% of sufferers, respectively, and dose interruptions had been noticed in 46%. The commonest any-grade AEs with zanubrutinib had been musculoskeletal ache (33%), higher respiratory tract an infection (28%), and hemorrhage (27%).2

Within the cohort of sufferers with a 17p deletion the speed of great AEs was 41% with pneumonia (8%) and second main malignancy (7%) having the very best incidence. Everlasting discontinuation and doe discount had been noticed in 5% of sufferers, respectively, and dose interruptions had been noticed in 51%. Musculoskeletal ache (38%), higher respiratory tract an infection 328%), and rash (28%) had been the commonest any-grade AEs.2

In ALPINE, severe AEs occurred in 42.0% of sufferers receiving zanubrutinib in contrast with 50.0% of sufferers receiving ibrutinib. Remedy discontinuation on account of AEs was 15.4% and 22.2%, respectively, and occasions resulting in loss of life was 10.2% in contrast with 11.1%. The commonest AEs had been neutropenia (16.0% vs 13.9%), hypertension (14.8% vs 11.1%), pneumonia (5.9% vs 8.0%), and COVID-19–associated pneumonia (7.1% vs 4.0%), respectively.

Sufferers taking zanubrutinib must be taught to report and indicators or signs of extreme bleeding or an infection. They need to be told that they’ll want periodic blood exams to observe for cytopenia. They need to be made conscious that different malignancies have been reported with zanubrutinib, and suggested to put on solar safety and monitor for different malignancies. They need to additionally report any indicators of palpitations, lightheadedness, dizziness, fainting, shortness of breath, and chest discomfort.2

Zanubrutinib may cause embryo-toxicity. Sufferers ought to use efficient contraception throughout therapy and for 1 week after the final therapy dose.2


  1. FDA approves zanubrutinib for persistent lymphocytic leukemia or small lymphocytic lymphoma. Information launch. FDA. January 19, 2023. Accessed January 19, 2023.
  2. Brukinsa. Prescribing data. BeiGene USA, Inc; 2023. Accessed January 19, 2023.


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