Evaluating the effectiveness and safety of zanubrutinib versus ibrutinib in patients with Waldenström Macroglobulinemia.

This study evaluated the effectiveness and safety of zanubrutinib (Brukinsa) versus ibrutinib (Imbruvica) in patients with Waldenström Macroglobulinemia (WM). The data showed that zanubrutinib had higher long-term response rates and lower side effects than ibrutinib in these patients.

WM is a type of cancer in which the bone marrow makes too many lymphocytes (a type of white blood cell). These lymphocytes produce a protein that accumulates in the blood and impairs blood circulation and causes complications. Highly effective targeted therapies have been developed for WM as it can be challenging to treat.

Zanubrutinib and ibrutinib are a type of targeted therapy known as Bruton tyrosine kinase (BTK) inhibitors. Ibrutinib is approved for the treatment of chronic lymphocytic leukemia (CLL). Zanubrutinib is approved for the treatment of mantle cell lymphoma (an aggressive type of lymphoma). However, the effectiveness and safety of zanubrutinib compared to ibrutinib in patients with WM are still unknown.

This study involved 229 patients with WM. Patients were divided into two groups. Group 1 included 201 patients with MYD88 mutations (gene mutated in 90% of WM cancers) who were randomly assigned to receive either zanubrutinib (160 mg twice daily) (102 patients) or ibrutinib (420 mg once daily) (99 patients). Group 2 included 28 patients without MYD88 mutations, who received zanubrutinib (160 mg twice daily). The average follow-up time was 43 months.

The average treatment duration was 42 months for zanubrutinib and 41 months for ibrutinib. 67% of the patients remained on treatment with zanubrutinib and 58% of the patients remained on treatment with ibrutinib.

In group 1, 36% of the patients who received zanubrutinib achieved complete response/very good partial response (CR+VGPR; complete or partial disappearance of cancer cells) versus 22% of the patients who received ibrutinib. In group 2, the CR+VGPR rate was 31%.

For patients with wild-type CXCR4 (gene mutated in 30-40% of WM cancers), the CR+VGPR rates were 45% with zanubrutinib versus 28% with ibrutinib. For patients with mutated CXCR4, the CR+VGPR rates were 21% with zanubrutinib versus 5% with ibrutinib.

Survival without cancer worsening and overall survival exceeded the average follow-up period in all patients. 

The rate of serious side effects was lower in patients who received zanubrutinib compared to patients who received ibrutinib. The most common side effects were irregular heartbeats, diarrhea, high blood pressure, bleeding, muscle spasms, and pneumonia.

This study concluded that zanubrutinib had higher long-term response rates and lower side effects than ibrutinib in patients with WM.

This study was sponsored by BeiGene, the manufacturer of zanubrutinib.