Zanubrutinib Continues to Exhibit Sustained Responses and Tolerable Safety Among Patients With R/R MZL

Final Analysis of the Phase 2 MAGNOLIA trial

Zanubrutinib continued to exhibit sustained responses and tolerable safety among patients with relapsed/refractory (R/R) marginal zone lymphoma (MZL) who had received at least 1 anti-CD20-directed regimen, according to the final analysis of the phase 2 MAGNOLIA trial. 

“In recent years, advances in the understanding of MZL have revealed the importance of the B-cell receptor signaling pathway and the involvement of Bruton tyrosine kinase (BTK) in the B-cell receptor’s downstream transduction pathway,” stated Stephen Opat, MD, Monash University, Clayton, Australia, and coauthors. This breakthrough in research led to the primary analysis of the phase 2 MAGNOLIA study, which assessed the impact of BTK inhibitor zanubrutinib on efficacy and safety among patients with R/R MZL. 

In this final analysis of the MAGNOLIA study, Opat and coauthors reassessed zanubrutinib among patients with R/R MZL who had received 1or more anti-CD20-directed regimen after an additional 12 months to determine the durability of responses and evaluate long-term safety outcomes. 

Zanubrutinib was administered at 160 mg twice daily to a total of 68 patients with R/R MZL who had received 1 or more anti-CD20-directed regimen until disease progression, unacceptable toxicity, or patient withdrawal occurred. All patients also had measurable disease or by computed tomography or magnetic resonance imaging, needed systemic MZL treatment as determined by the study investigators, had adequate bone marrow and organ function, and had an Eastern Cooperative Oncology Group (ECOG) performance status score of 0 to 2. The primary end point was the overall response rate, assessed by the independent review committee. Secondary end points included the overall response rate evaluated by the study investigators, duration of response, progression-free survival, overall survival, quality of life, safety, and tolerability. 

At a median follow-up of 27.4 months, the overall response rate as assessed by the independent review committee was 68.2%, and the 24-month duration of response rate, event-free, was 72.9%. At 24 months, the progression-free survival and overall survival were 70.9% and 85.9%.
Safety outcomes were consistent with the primary analysis, with no new safety signals noted. The most common grade 3 or higher adverse event was neutropenia, occurring in 8 patients. Atrial fibrillation/flutter and hypertension were uncommon. 

Opat and study authors concluded, “zanubrutinib demonstrated sustained clinical responses beyond 2 years, with 73% of responders alive and progression free.”

“Zanubrutinib continued to demonstrate a favorable safety/tolerability profile with the additional time on treatment,” they added. 

Source: 

Opat S, Tedeschi A, Hu B, et al. Safety and efficacy of zanubrutinib in relapsed/refractory marginal zone lymphoma: final analysis of the MAGNOLIA study. Blood Adv. Published online: November 15, 2023. doi: 10.1182/bloodadvances.2023010668