Histologic Transformation in Follicular Lymphoma: Real-World Outcomes with Rituximab vs. Obinutuzumab-Based Combinations

Background/Objectives: The survival of patients experiencing transformation of follicular lymphoma (tFL) is generally inferior to that of their non-transformed FL counterparts. While rituximab (R) has been shown to reduce transformation rates, data on Obinutuzumab (O), a third generation anti-CD20 monoclonal antibody, are limited. Methods: This retrospective study analyzed risk factors for tFL and evaluated outcomes following transformation in 1145 consecutive patients with FL (2010–2023). Results: Over a median follow-up of 70 months, 9% (n = 103) of FL patients developed tFL, with a median time of 36 months from FL diagnosis to transformation. In multivariate analysis, O-based, compared to R-based regimens and maintenance therapy (compared to no maintenance), were independently associated with reduced risk of histologic transformation (HR 0.40, 95% CI 0.19–0.90, p = 0.026 and HR 0.42, 95% CI 0.23–0.77, p = 0.005, respectively). Transformed FL was associated with shorter overall survival (OS) from FL diagnosis compared to non-transformed FL (median not reached, p < 0.001), while prior exposure to anti-FL chemoimmunotherapy predicted shorter OS following transformation (median 34.6 months vs. not reached, p = 0.001). Multivariate analysis confirmed prior exposure to anti-FL therapy (HR 5.27, p < 0.001), male sex (HR 2.36, p = 0.014), and age over 65 (HR 2.54, p = 0.019) to be associated with shorter OS among patients with tFL. Conclusions: These findings, although requiring further validation, suggest that O-based regimens may reduce the risk of transformation and support prior studies demonstrating adverse survival outcomes in previously treated tFL patients.