• Center on Health Equity and Access
  • Clinical
  • Health Care Cost
  • Health Care Delivery
  • Insurance
  • Policy
  • Technology
  • Value-Based Care

Abstracts Demonstrate Long-term, Real-world Advantages of Zanubrutinib in WM


In abstracts featured at the 2022 European Hematology Association Congress, investigators detailed long-term results of the ASPEN phase 3 trial and an expanded access study of zanubrutinib in patients with Waldenström macroglobulinemia (WM).

In abstracts featured at the 2022 European Hematology Association (EHA) Congress, investigators detailed long-term results of the ASPEN phase 3 trial and an expanded access study of zanubrutinib in patients with Waldenström macroglobulinemia (WM).

The first abstract presented findings from the randomized, phase 3 ASPEN trial in 2 cohorts: one comparing the efficacy and safety of the next-generation Bruton tyrosine kinase (BTK) inhibitor zanubrutinib against the first-generation BTK inhibitor ibrutinib in patients with MYD88-mutant WM, and the other assessing zanubrutinib in patients with wild-type MYD88 WM.1 The abstract noted that ASPEN is the largest phase 3 trial to offer head-to-head comparison of the BTK inhibitors in WM.

Cohort 1 enrolled 201 patients (zanubrutinib, n = 102; ibrutinib, n = 99) and cohort 2 enrolled 28 patients. The primary end point was the percentage of patients achieving very good partial response (VGPR) or better (complete response [CR]) as assessed by investigators. After a median treatment duration of 44.1 months, the VGPR+CR rates were 36% for zanubrutinib and 22% for ibrutinib in cohort 1 (P = .02) and 31% in cohort 2. Median progression-free survival (PFS) and overall survival (OS) were not reached, but rates of both continued to favor zanubrutinib treatment in both cohorts.

The investigators also assessed outcomes by CXCR4 mutational status in cohort 1 and found that VGPR+CR rates with zanubrutinib vs ibrutinib were 45% vs 28%, respectively (P = .04), for those with wild-type CXCR4 and 21% vs 5% (P = .15) for those with mutant CXCR4.

Further, they observed lower rates of most adverse events (AEs) and of AEs leading to treatment discontinuation or death in the patients receiving zanubrutinib vs ibrutinib, which the researchers noted was consistent with “less off-target inhibition” with the next-generation BTK inhibitor. Notably, the rate of hemorrhage was 62.2% in the cohort 1 ibrutinib group vs 55.4% and 39.3% in the zanubrutinib groups in cohorts 1 and 2, respectively. There was a higher rate of neutropenia in the zanubrutinib arm, but this AE tended to occur early and the prevalence decreased over time.

The abstract concluded that zanubrutinib “was associated with a higher VGPR+CR rate and demonstrated clinically meaningful advantages in long-term safety and tolerability” vs ibrutinib.

In the second abstract, investigators presented real-world findings of a phase 2 expanded-access study of zanubrutinib in patients with WM.2 A total of 50 patients with WM (treatment naïve, n = 17; relapsed/refractory, n = 33) were enrolled at 10 academic and community medical centers in the United States. Median treatment exposure was 9.2 months (range, 1.4-20.0 months), and median patient age was 72 years at study entry.

Patients received zanubrutinib as monotherapy at a daily dose of 320 mg, either once a day or as 120 mg twice a day.

Just over three-quarters (76.0%) of the patients experienced at least 1 treatment-emergent AE (TEAE), and 72.0% experienced at least 1 TEAE of special interest, which included hypertension, infection, atrial fibrillation or flutter, neutropenia, and second primary malignancy.

Of the 41 patients whose responses were evaluated, 39.0% achieved a best overall response of VGPR. The overall response rate was 85.4% (95% CI, 70.8%-94.4%), and the major response rate was 73.2% (95% CI, 57.1%-85.8%). The investigators could not assess PFS and OS due to the relatively short follow-up time.

The poster presented at EHA2022 noted that this study demonstrated a higher VGPR rate, a similar major response rate, and a lower overall response rate compared with the ASPEN study. According to the authors, the latter may be attributed to the 6-month intervals between response assessments in this study, as they would not have been able to capture responses that were achieved between the response assessments.

Additionally, they noted the differences in demographic and baseline disease characteristics in their cohort compared with the ASPEN trial participants. Stemming from this cohort’s real-world nature, these patients tended to be older and have worse ECOG performance scale scores, longer duration of disease course, and worse prognosis. These differences make the comparable response rates and toxicity profiles between the 2 studies all the more notable.

“The results of this real-world expanded access study were consistent with the established [zanubrutinib] profile in WM,” the authors concluded. They noted that when the study closed in July 2021, patients still active on zanubrutinib were helped to transition to the commercially sold drug via a patient assistance program.


1. Dimopoulos M, Opat S, D’Sa S, et al. ASPEN: long-term follow-up results of a phase 3 randomized trial of zanubrutinib (ZANU) vs ibrutinib (IBR) in patients (pts) with Waldenström macroglobulinemia (WM). HemaSphere. 2022;6(suppl 3):P1161.

2. Castillo JJ, Kingsley EC, Narang M, et al. Results of a phase 2 expanded access study of zanubrutinib in patients with Waldenström macroglobulinemia. HemaSphere. 2022;6(suppl 3):P1160.

Related Videos
Camilla Levister
dr daniel ontaneda
Sudipto Mukherjee, MD, PhD, MPH, hematology and medical oncology, Cleveland Clinic
Video 12 - "Key Considerations for Treating Patients Diagnosed With CLL and SLL"
Video 11 - "Optimizing BTKi Treatment Strategies"
Video 13 - "Other Clinical Considerations in Demodex Blepharitis Treatment"
Video 12 - "Cost-Effective Medication Access in Demodex Blepharitis Management"
Video 10 - "Patient Education Drives BTK Inhibitor Treatment Adherence"
Related Content
© 2024 MJH Life Sciences
All rights reserved.