Blood Adv

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 II 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 one prior anti-CD20-based regimen. The median age at zanubrutinib initiation was 75 years, and 56% were female. MZL subtypes included splenic (55.3%), MALT (18.9%), nodal (19.8%), and non-classifiable (6%). The median number of prior lines of therapy (LoT) was 1.5 (range 1-7); 26% were refractory to the immediately preceding line, and 59% were POD24 to frontline. Thirty-one patients (26.3%) would not have met MAGNOLIA 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 eligibility. Fewer prior 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 cases with progressing disease (p < 0.01). Adverse events (AEs) were reported in 34.1% of patients (grade ≥ 3 in 14.4%). MAGNOLIA-ineligible patients experienced a higher incidence of AEs, and bleeding events were more frequent among patients receiving anticoagulant therapy (p = 0.04). Overall, zanubrutinib demonstrated favorable effectiveness and safety in real-world R/R MZL, with improved outcomes when administered earlier in the disease.