BTK Inhibitor Zanubrutinib Appears Promising in Waldenström Macroglobulinemia

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BeiGene released results from its phase 1 clinical trial of the investigational BTK inhibitor zanubrutinib.
BeiGene released results from its phase 1 clinical trial of the investigational BTK inhibitor zanubrutinib.

Zanubrutinib was well tolerated and highly active in patients with Waldenström macroglobulinemia (WM), with more than 90% of patients experiencing a response, according to phase 1 data that were presented at the 10th International Workshop on Waldenström's Macroglobulinemia (IWWM).1

Zanubrutinib is a Bruton's tyrosine kinase (BTK) inhibitor. BTK is known to play a critical role in B-cell receptor signaling, which mediates cell proliferation, migration, and adhesion.

At data cutoff in July 2018, the study included 77 patients with treatment-naive or relapsed/refractory WM; 73 patients were evaluable for efficacy.

The median follow-up time was 22.5 months. The overall response rate was 91.8%, including 41.1% of patients with a very good partial response.

There was increased depth of response over time. In the 46 patients with more than 1 year of follow-up, only 4.3% had achieved very good partial response up to week 14, but up to week 26 this increased to 15.2%, and up to 1 year, it was 32.6%.

The estimated 12-month progression-free survival in evaluable patients through 36 months of follow-up was 89%. Median progression-free survival had not yet been reached.

The researchers also looked at efficacy in a subset of 54 patients with a MYD88L255P mutation. In this group, there was an overall response rate of 94% with very good partial response in 46% of patients. Patients who were known to be MYD88WT—a characteristic that is normally tied to a suboptimal response to BTK inhibitors—had an overall response rate of 94% to the investigational drug, with a major response rate of 89%.

Treatment discontinuation due to adverse events occurred in 11.7% of patients, but was determined not to be related to the investigational agent. Common grade 3/4 adverse events included neutropenia, anemia, hypertension, basal cell carcinoma, renal and urinary disorders, and pneumonia. Forty-two percent of patients had serious adverse events, with 7% of them considered to be related to zanubrutinib.

BeiGene expects to file a new drug application with the US Food and Drug Administration during the first half of 2019.


  1. BeiGene, LTD. BeiGene announces updated results from phase 1 clinical trial of zanubrutinib in patients with Waldenström's Macroglobulinemia. Published October 12, 2018. Accessed October 16, 2018.

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