Zanubrutinib is as effective as — but safer than — ibrutinib for patients with Waldenström macroglobulinemia (WM), according to research published in the Journal of Clinical Oncology.

Researchers compared zanubrutinib and ibrutinib in WM patients enrolled in the phase 3 ASPEN trial ( Identifier: NCT03053440).

Patients were enrolled in 2 cohorts. Cohort 1 included 201 patients with MYD88-mutant WM who were randomly assigned to receive zanubrutinib (n=102) or ibrutinib (n=99). Cohort 2 included 28 patients with wild-type MYD88 who received zanubrutinib.

At a median follow-up of 44.4 months for patients with MYD88-mutant WM, the proportion of patients still on treatment was 65.7% in the zanubrutinib arm and 51.5% in the ibrutinib arm. At a median follow-up of 42.9 months for patients with MYD88 wild-type WM, the proportion of patients still on zanubrutinib was 35.7%.

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The study’s primary endpoint was the sum of very good partial response (VGPR) and complete response (CR) rates.

In patients with MYD88-mutant WM, the VGPR rate was 36.3% with zanubrutinib and 25.3% with ibrutinib. There were no CRs. Among patients in this cohort with CXCR4 mutations, the VGPR rate was 21.2% with zanubrutinib and 10.5% with ibrutinib.

The median duration of response was not reached in either arm of the MYD88-mutant cohort. The median time to VGPR was faster with zanubrutinib than with ibrutinib — 6.7 months and 16.6 months, respectively.

In patients with MYD88-mutant WM, there were no significant differences in progression-free survival (PFS) or overall survival (OS). The median PFS and OS were not reached in either arm (P =.12 for PFS; P =.45 for OS). At 42 months, the PFS rate was 69.7% in the ibrutinib arm and 78.3% in the zanubrutinib arm. The 42-month OS rate was 85.2% and 87.5%, respectively.

In patients with MYD88 wild-type WM, the VGPR/CR rate was 30.8%, with 1 CR. The researchers noted that, in previous studies, no patients with wild-type MYD88 achieved a major response with ibrutinib or a VGPR/CR with acalabrutinib.

Among MYD88 wild-type patients, the median time to VGPR/CR was 6.88 months, and the median duration of response was not reached. The median PFS was 45.8 months, and the median OS was not reached. At 42 months, the PFS rate was 53.8%, and the OS rate was 83.9%.

In the cohort with MYD88-mutant WM, several adverse events (AEs) occurred more often with ibrutinib than with zanubrutinib. However, neutropenia was initially more common with zanubrutinib than with ibrutinib.

“Extended follow-up results confirm improved long-term safety and tolerability of zanubrutinib compared with ibrutinib and support deeper, earlier, and more durable responses in patients with WM regardless of previous treatment or CXCR4 and MYD88 mutational statuses,” the researchers concluded.

Disclosures: This research was supported BeiGene. Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.


Dimopoulos MA, Opat S, D’Sa S, et al. Zanubrutinib versus ibrutinib in symptomatic Waldenström macroglobulinemia: Final analysis from the randomized phase III ASPEN study. J Clin Oncol. Published online July 21, 2023. doi:10.1200/JCO.22.0283

This article originally appeared on Cancer Therapy Advisor