Zanubrutinib in relapsed/refractory marginal zone lymphoma: Final results from the MAGNOLIA study

The MAGNOLIA study (NCT03846427) evaluated the efficacy, safety, and tolerability of zanubrutinib, a next-generation Bruton’s tyrosine kinase inhibitor, in patients with relapsed/refractory (R/R) marginal zone lymphoma (MZL). The primary analysis of the MAGNOLIA study, previously reported on the Lymphoma Hub, demonstrated a high overall response rate (ORR) with a favorable safety profile. These key results led to the European Commission approval of zanubrutinib for the treatment of adult patients with R/R MZL who had received at least one prior line of anti-CD20-based therapy.

Here, we summarize the final results of the MAGNOLIA study, published by Opat et al.¹ in Blood Advances, highlighting the durable responses and longer-term safety and tolerability of zanubrutinib in patients with R/R MZL.

Study design

MAGNOLIA was an open-label, single-arm, multicenter phase II study evaluating the efficacy and safety of zanubrutinib for the treatment of patients with R/R MZL who had received at least one anti-CD20-directed regimen. All patients were treated with oral zanubrutinib at a dose of 160 mg twice daily until disease progression, unacceptable toxicity, or patient withdrawal.

The primary endpoint was ORR defined as the percentage of patients achieving the best overall partial response or complete response, as assessed by an independent review committee.

Secondary endpoints included investigator-assessed ORR, duration of response (DOR), progression-free survival (PFS), and overall survival (OS). Health-related quality of life and safety/tolerability were also assessed.

Results

Patient characteristics for the treated cohort (n = 68) have been previously reported on the Lymphoma Hub.

Efficacy¹

A total of 66 patients were included in the analysis and two patients were excluded due to a confirmed diagnosis of diffuse large B-cell lymphoma during a central review

With a median follow-up of 27.4 months, the independent review committee assessed ORR was 68.2% (95% CI, 55.6–79.1%; p < 0.001 vs the null hypothesis), consistent with the primary analysis. The response rates across MZL subtypes are shown in Table 1.

Table 1. IRC-assessed disease responses by MZL subtypes*

Median PFS and DOR were not reached at a median follow-up of 27.4 and 23.4 months, respectively. At 24 months, PFS and DOR rates were 70.9% (95% confidence interval [CI], 57.2–81.0%) and 72.9% (95% CI, 54.4–84.9%), respectively.

Subgroups of patients who traditionally respond poorly to therapy demonstrated higher response rates than those seen in the overall study population. These subgroups included ≥75 years of age (94.4%), male (83.3%), >2 years since last anti-lymphoma therapy (79.3%), relapsed disease (72.1%), at least one target lesion >5 cm (79.2%), nodal MZL subtype (76.0%), Stage IV disease (70.0%), prior treatment with rituximab monotherapy (100.0%), prior treatment with rituximab, cyclophosphamide, vincristine and prednisolone (80.0%).

Safety/tolerability¹

All patients reported at least one treatment-emergent adverse event of any grade (Table 2). Grade ≥3 adverse events of special interest were infrequent. Overall, the safety profile of zanubrutinib remained consistent with the primary analysis, and no additional late-onset toxicities or new safety signals were observed.

Table 2. Summary of adverse events*

Conclusion

Results from the final analysis of the MAGNOLIA trial were consistent with the primary analysis, demonstrating high efficacy and tolerability. No additional late-onset toxicities or safety signals were observed after longer treatment duration and follow-up, showing that zanubrutinib provides durable disease control with a favorable safety profile in patients with R/R MZL.