FDA Approves Zanubrutinib for Waldenstrom Macroglobulinemia

Non-Hodgkin lymphoma.

The FDA has granted approval to zanubrutinib (Brukinsa®, BeiGene) for the treatment of patients with Waldenstrom macroglobulinemia (WM).

“Bruton tyrosine kinase (BTK) inhibition is an emerging standard of care for WM,” wrote Constantine Si Lun Tam, MBBS, MD, FRACP, FRCPA, Professor at the Peter MacCallum Cancer Centre in Australia, and colleagues, in their publication of the ASPEN study results (NCT03053440), on which the approval was based. “ASPEN is a randomized phase 3 study comparing zanubrutinib, a potent and selective BTK inhibitor, versus ibrutinib, a first-generation BTK inhibitor, in WM patients.”

A total of 229 patients enrolled in this active control, open-label clinical trial. Patients in Cohort 1 (n=201) were randomized 1:1 to receive zanubrutinib 160 mg twice daily or ibrutinib 420 mg once daily until disease progression or unacceptable toxicity. The remaining patients were assigned to Cohort 2 because they either had MYD88 wild-type WM or MYD88 mutation unknown WM (n=26 and n=2, respectively); they received 160 mg zanubrutinib twice daily. The primary end point was the response rate, defined as partial response or better. The secondary end point was duration of response.

Zanubrutinib produced a response rate of 77.5% with a 12-month event-free duration of response rate of 94.4%. In Cohort 2, the response rate was 50%.

The most common adverse events and laboratory abnormalities occurring in at least 20% of patients were neutrophil count decrease, upper respiratory tract infection, platelet count decrease, rash, hemorrhage, musculoskeletal pain, hemoglobin decrease, bruising, diarrhea, pneumonia, and cough.

“Although not statistically significant, zanubrutinib was associated with a higher complete response or very good partial response rate, and demonstrated clinically meaningful advantages in safety and tolerability compared to ibrutinib,” concluded Dr. Tam and colleagues in their May 2020 abstract, presented at the American Society of Clinical Oncology (ASCO) Annual Meeting and published in the Journal of Clinical Oncology.

The recommended dose of zanubrutinib is 160 mg orally twice daily or 320 mg orally once daily.

For More Information

Tam CSL, Opat S, D’Sa S, et al (2020). ASPEN: results of a phase III randomized trial of zanubrutinib versus ibrutinib for patients with Waldenström macroglobulinemia (WM). J Clin Oncol (ASCO Annual Meeting Abstracts), 38(suppl_15). Abstract 8007. DOI:10.1200/JCO.2020.38.15_suppl.8007

Clinicaltrials.gov (2021). A study comparing BGB-3111 and ibrutinib in participants with Waldenström’s macroglobulinemia (WM) (ASPEN). NLM identifier: NCT03053440.

Brukinsa® (zanubrutinib) prescribing information (2021). BeiGene. Available at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/213217Orig1s004lbl.pdf

US Food & Drug Administration (2021). FDA approves zanubrutinib for Waldenström’s macroglobulinemia. Available at: https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-zanubrutinib-waldenstroms-macroglobulinemia

Image credit: Jensflorian. Licensed under CC BY-SA 3.0

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