Real-world effectiveness and safety of zanubrutinib in Spanish patients with relapsed/refractory marginal zone lymphoma

Abstract: There is no established standard treatment of relapsed/refractory (R/R) marginal zone lymphoma (MZL). Zanubrutinib was approved in this setting based on the phase 2 MAGNOLIA trial. We retrospectively evaluated the characteristics and outcomes of 118 real-world patients in Spain with R/R MZL treated with zanubrutinib after at least 1 previous anti-CD20–based regimen. The median age at zanubrutinib initiation was 75 years, and 56% were female. MZL subtypes included splenic (55.3%), mucosa-associated lymphoid tissue (18.9%), nodal (19.8%), and nonclassifiable (6%). The median number of previous lines of therapy (LoT) was 1.5 (range, 1-7); 26% of patients had MZL refractory to the immediately preceding line, and 59% experienced progression of disease within 24 months (POD24) to frontline therapy. In total, 31 patients (26.3%) would not have met MAGNOLIA trial eligibility criteria, 68% had cardiovascular comorbidities, and 28% were receiving antithrombotic therapy. The overall and complete response rates were 76% and 22.2%, respectively, with no differences according to MZL subtype, age, POD24, or MAGNOLIA trial eligibility. Fewer previous LoT were associated with higher and deeper responses. With a median follow-up of 14 months, 1-year progression-free and overall survival were 79.4% and 86.8%, respectively. Zanubrutinib responders and patients with stable disease presented better outcomes than those with progressing disease ( P < .01). Adverse events (AEs) were reported in 34.1% of patients (grade ≥3 in 14.4%). MAGNOLIA trial–ineligible patients experienced a higher incidence of AEs, and bleeding events were more frequent among patients receiving anticoagulant therapy ( P = .04). Overall, zanubrutinib demonstrated favorable effectiveness and safety in real-world R/R MZL, with improved outcomes when administered earlier in the disease.