Details of the final analysis of the phase III ASPEN trial, which compared zanubrutinib and ibrutinib in symptomatic patients with Waldenström’s macroglobulinemia, were published in the Journal of Clinical Oncology by Meletios A. Dimopoulos, MD, and colleagues.
The study supported the September 2021 approval of zanubrutinib in this setting.
As stated by the investigators, “The phase III ASPEN study demonstrated the comparable efficacy and improved safety of zanubrutinib vs ibrutinib in patients with Waldenström’s macroglobulinemia. Here, we report long-term follow-up outcomes from ASPEN.”
Meletios A. Dimopoulos, MD
Study Details
In the open-label trial, 201 patients with MYD88-mutant disease (cohort 1) were randomly assigned to receive zanubrutinib at 160 mg twice daily (n = 102) or ibrutinib at 420 mg once daily (n = 99). A total of 28 patients with wild-type MYD88 (cohort 2) received zanubrutinib at 160 mg twice daily. The primary endpoint was the sum of the very good partial response and complete response rates.
Key Findings
At a median follow-up of 44.4 months (range = 0.4–57.3 months), 65.7% of patients on zanubrutinib and 51.5% on ibrutinib in cohort 1 remained on treatment. Rates of very good partial response plus complete response were 36.3% (95% confidence interval [CI] = 27.0%–46.4%) with zanubrutinib vs 25.3% (95% CI = 17.1%–35.0%) with ibrutinib (P = .07). At a median follow-up of 42.9 months (range = 2.3–53.7 months), 35.7% of patients in cohort 2 remained on zanubrutinib; the rate of very good partial response plus complete response was 30.8% (95% CI =14.3%–51.8%).
Among 33 patients on zanubrutinib and 20 patients on ibrutinib in cohort 1 with CXCR4 mutations, very good partial response plus complete response rates were 21.2% (95% CI = 9.0%–38.9%) vs 10.0% (95% CI = 1.2%–31.7%).
Median progression-free survival and overall survival were not reached in either group in cohort 1. The zanubrutinib group had nonsignificantly fewer progression-free survival events (hazard ratio [HR] = 0.63, 95% CI = 0.36–1.12) and overall survival events (HR = 0.75, 95% CI = 0.36–1.59). In the two groups in cohort 1, progression-free survival at 42 months was 78.3% vs 69.7% and overall survival at 42 months was 87.5% vs 85.2%. In cohort 2, progression-free and overall survival at 42 months were 53.8% and 83.9%, respectively.
In cohort 1, any-grade adverse events of diarrhea (34.7% vs 22.8%), muscle spasms (28.6% vs 11.9%), hypertension (25.5% vs 14.9%), atrial fibrillation/flutter (23.5% vs 7.9%), and pneumonia (18.4% vs 5.0%) were more common in the ibrutinib group; neutropenia (20.4% vs 34.7%) was less common with ibrutinib. Adverse events led to treatment discontinuation in 8.9% of patients in the zanubrutinib group vs 20.4% of the ibrutinib group (P < .05).
The investigators concluded, “Overall, these findings confirm the long-term response quality and tolerability associated with zanubrutinib.”
Dr. Dimopoulos, of the School of Medicine, National and Kapodistrian University of Athens, is the corresponding author for the Journal of Clinical Oncology article.
Disclosure: The study was supported by BeiGene. For full disclosures of the study authors, visit ascopubs.org.
