Prognostic factors and response to fludarabine therapy in Waldenstrom's macroglobulinemia: An update of a US intergroup trial (SW0G S9003)

We report an update on a prospective observational trial for Waldenstrom's macroglobulinemia (WM) that called for re-registration to treatment with fludarabine (30 mg/m²) upon the development of symptomatic or progressive disease. Patients who did not require therapy for more than 1 year (n = 54) could be distinguished from the 118 untreated patients requiring immediate therapy on the basis of hemoglobin, serum β₂-microglobulin (β2m), C-reactive protein (CRP), albumin, and IgM levels, and lower incidence of extramedullary infiltration. Overall response rate (≥ partial response [PR]) to fludarabine was 38%, with 2% complete remissions (CRs). Event-free and overall survivals were significantly longer in the presence of lower levels of serum β2m in all cohorts. Using time-dependent covariates, neither the occurrence of response (≥ PR) nor the time to response was associated with superior overall or event-free survival. These data support serum β2m as the dominant prognostic indicator in WM, and show that this factor alone can provide valuable disease risk assessment. Response to therapy using current criteria is not a reliable predictor for survival in this disease.