Challenges in predicting outcomes for watch and wait follicular lymphoma patients: insights into clinical, pathological, and molecular factors

Follicular lymphoma (FL) exhibits considerable heterogeneity in clinical trajectories and molecular characteristics. This study assessed the association between clinical presentation, histopathological findings, and mutational profiles with the duration of a Watch-and-Wait (WW) strategy in a cohort of 124 FL patients managed with a WW approach at diagnosis. Median event-free survival (EFS) (time to treatment or death) was 29 months. Hemoglobin below <12 g/dL and a Ki-67 proliferation index ≥30% were associated with inferior EFS. Mutational analyses showed considerable variability between patients. <i>B2M</i> mutations and high m7-FLIPI score correlated with inferior EFS, though present in only 4% and 15% of cases, respectively. WW patients were compared to 91 patients receiving upfront immunochemotherapy to evaluate the differences in prognostic factors and mutational profiles. Despite distinct clinical prognostic factors, mutational profiles were comparable between the two groups, even at clinical extremes. These findings underscore the challenges in predicting the duration of a WW approach.