P110 | ZANUBRUTINIB IN WALDENSTROM MACROGLOBULINEMIA. REPORT ON THE EXPERIENCE OF THE CAMPANIA GROUP ON CLL/WM: THE DIAGNOSTIC AND INTEGRATED DIRECTION FOR OPTIMIZED CAMPANIA NETWORKING IN WALDENSTROM DISEASE (DIDONE) PROJECT.

Waldenström macroglobulinemia (WM) is a rare lymphoplasmacytic lymphoma with immunoglobulin M (IgM) monoclonal protein whose clinical features include anemia, thrombocytopenia, hepatosplenomegaly, lymphadenopathy, and more rarely hyperviscosity. Bruton tyrosine kinase (BTK) inhibitors are approved in many hematologic malignancies such as chronic lymphocytic leukemia, mantle cell lymphoma, marginal zone lymphoma, follicular lymphoma and WM. Zanubrutinib is a second-generation BTK inhibitor displaying high target selectivity and reduction of off-target effects with better therapeutic index and improved tolerability. Here we report the preliminary data of a multicenter retrospective study by Campania Group on CLL/WM on therapy with zanubrutinib in WM patients, naive (TN) and relapsed/refractory (R/R), as well. They were treated at our Institutions between February 15th, 2023 and March 30th, 2025 according to the Diagnostic and Integrated Direction for Optimized campania Networking in waldEnström&#x27;s disease (DIDONE) project. Thyrty-two patients diagnosed with WM were retrospectively evaluated (M 21; F 11; mean age 74,6 years; range 56-89 years); 24 patients were TN WM patients (M 13; F 11; mean age 71,7 years; range 56-88 years), while 8 were R/R WM patients (M 6; F 2; mean age 75,5 years, range 57-89 years). At baseline patients showed a mean IgM 4,4 g/dl (range 1-8,9 g/dl) and a mean clonal lymphoplasmacytic cell infiltration in bone marrow 54% (range 15-80%). Furthermore, L265P mutation in MYD88 was detectable in all patients while CXCR4 only in 6. More common comorbidities were hypertension, diabetes, chronic ischemic hearth disease, and atrial fibrillation (in 3 patients). Zanubrutinib (Brukinsa) was given at a standard dose of 160 mg orally twice daily. At this time (April 30th, 2025) 23 patients were evaluable for response. An overall response rate was 91%: 9 patients (39%); 3 very good partial response (14%), 8 partial response 38%), 1 patient with a minor response (5%). This latter displayed CXCR4 mutation while p53 was found negative). Finally, only 2 patients showed a stable disease. Any-grade treatment adverse events (AEs) occurred in 4 patients (12,5%: ecchymoses in 2 patients, 1 patient displayed a mild thrombocytopenia while one patient showed vitreous hemorrage and therapy discontinuation. In conclusion, this real world study, despite limited in number and with a short follow-up (<18 months), showed that in our hands also zanubrutinib is safe and effective in patients with both TN and R/R WM.