P015 | FEATURES AND OUTCOMES OF ASYMPTOMATIC WALDENSTRÖM MACROGLOBULINEMIA IN RELATION TO BONE MARROW INFILTRATION: AN ITALIAN UNIVERSITY HOSPITAL ANALYSIS

Studies have suggested that the size of the bone marrow neoplastic lymphoplasmacytic infiltrate holds prognostic value for the time to progression from asymptomatic to symptomatic Waldenstrom Macroglobulinemia (WM). We conducted an analysis on 230 patients with WM diagnosed (2005-2025) at the Hematology Unit of the University of Padua Hospital aiming at assessing the impact of lymphoplasmacytic cell bone marrow (BM) infiltration in predicting both the transition from asymptomatic to symptomatic WM and time to next treatment for symptomatic WM. Time to first treatment (TTFT) was evaluated for asymptomatic patients at diagnosis; event free survival (EFS) for the entire cohort, with the event defined as either transformation from asymptomatic to symptomatic or initiation of second line treatment. To classify high vs low tumor burden, we used the median value of BM infiltration as a cutoff for both groups. The asymptomatic cohort at diagnosis (n=150) was stratified into high (>= 25%, n = 82) and low (<25%, n = 68) BM infiltration subgroups. The first one displayed distinct clinical features: mild anemia (126.6 vs 134.5, p=0.001), higher serum IgM levels (19.0 g/L vs 10.1 g/L, p<0.001), higher serum monoclonal component (MC) levels (14.6 g/L vs 7.7 g/L, p<0.001), higher frequency of CXCR4MUT (23% vs 13% p<0.001), lower prevalence of peripheral neuropathy (13% vs 30%, p=0.009). Median TTFT was significantly lower (64 vs 137 months, p =0.01) in the high BM infiltrate subgroup. In the univariate model shorter TTFT was associated with advanced age (HR 1.04), low Hb level (HR 1.02), high serum MC (HR 1.06) and IgM concentrations (HR 1.06) and the presence of cytogenetics aberrations (HR 2.5). In the multivariate analysis, only elevated IgM level (HR 1.09) resist with a trend to significance for the presence of cytogenetic aberrations (HR 2.4). For the entire cohort, a median BM infiltration of 30% equally differentiate the two subgroups with a trend to a lower median EFS (68 vs 128 months, p =0.08) for those with higher BM tumor burden. Finally, TTFT was significantly shorter for asymptomatic patients with high BM tumor burden showing higher prevalence of hyperviscosity, anemia and CXCR4MUT but less frequent neuropathy. Elevated serum IgM levels independently linked to inferior TTFT while the presence of cytogenetic abnormalities showed only a trend. These findings emphasize the prognostic value of BM disease burden as suggested by WHO-HEM 5 classification.