Among some patients with Waldenström macroglobulinemia (WM), zanubrutinib may improve the chance of a very good partial response (VGPR) or complete response (CR) compared with ibrutinib, according to research presented at the 2022 ASCO Annual Meeting.

Previous data have suggested that zanubrutinib, a selective, potent inhibitor of Bruton tyrosine kinase, may improve responses compared with ibrutinib, a first-generation inhibitor of the same target. The phase 3 ASPEN study (ClinicalTrials.gov Identifier: NCT03053440) was designed to investigate these 2 therapies in WM. The investigators of the ASPEN trial presented 43-month follow-up data at ASCO 2022.

ASPEN consisted of 2 cohorts: patients with MYD88 mutations and those without. In cohort 1, patients were randomly assigned 1:1 to the zanubrutinib or ibrutinib group; in cohort 2, all patients received zanubrutinib. The study’s primary endpoint was the CR plus VGPR rate.


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Overall, 201 and 28 patients were enrolled to cohorts 1 and 2, respectively. In cohort 1, more patients assigned to receive zanubrutinib had CXCR4 mutations (32% vs 20% in the ibrutinib group) and more were older than 75 years (33% vs 22%, respectively).

Patients who received zanubrutinib had a median duration of treatment of 42 months, and 67% of patients remained on treatment at the time of analysis; in the ibrutinib group, these statistics were 41 months and 58%, respectively.

By investigator assessment, the CR plus VGPR rate in cohort 1 was 36% with zanubrutinib vs 22% with ibrutinib (P =.02). In cohort 2, the CR plus VGPR rate was 31%; 1 patient in cohort 2 had a CR.

Patients with wild-type CXCR4 in cohort 1 had a greater response rate (45%) than did patients with mutated CXCR4 (21%); in the latter case, the response rate was not better than that seen with ibrutinib (P =.15).

In cohort 1, grade 3 or worse adverse events occurred in 74.3% of patients who received zanubrutinib and 72.4% of patients who received ibrutinib; this was true of 71.4% of patients in cohort 2. In the zanubrutinib and ibrutinib groups of cohort 1, and in cohort 2, the rates of adverse events leading to treatment discontinuation were 8.9%, 19.4%, and 14.3%, respectively.

Disclosure: The study author(s) declared affiliations with biotech, pharmaceutical, or device companies. Please see the original reference for a full list of authors’ disclosures.

Reference

Si Lun Tam C, Garcia-Sanz R, Opat S, et al. ASPEN: Long-term follow-up results of a phase 3 randomized trial of zanubrutinib (ZANU) versus ibrutinib (IBR) in patients with Waldenström macroglobulinemia (WM). Presented at: ASCO 2022; June 3-7, 2022. Abstract 7521.