Rituximab in the first-line setting may play a protective role in preventing the histological transformation of follicular lymphoma (FL) to aggressive lymphoma, according to a study published in The Lancet Haematology.1

One of the most serious clinical events that may occur during the course of FL is its transformation to a more aggressive subtype of lymphoma, most commonly, diffuse large B-cell lymphoma. The introduction of rituximab has greatly improved outcomes among patients with FL, but its impact on the risk of transformation, as well as outcomes post-transformation, are unclear. 

For the long-term, retrospective Aristotle study, researchers evaluated the outcomes of 10,001 newly diagnosed patients with grade 1, 2 or 3a FL. Transformation was defined as biopsy-proven aggressive lymphoma that occurred as a first event after first-line therapy. 

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Of 8116 eligible patients, 509 underwent transformation. 

After a median follow-up of 87 months, the overall 10-year cumulative hazard of histological transformation was 7.7%; patients who received rituximab compared with those who did not had a 10-year cumulative hazard of histological transformation of 5.2% and 8.7%, respectively (hazard ratio [HR], 0.73; 95% CI, 0.58-0.90; P= .004). 

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The 10-year cumulative hazard of histological transformation among patients treated with rituximab only as induction therapy was 5.9%, and was 3.6% among patients who received rituximab as induction and maintenance therapy (HR, 0.55; 95% CI, 0.37-0.81; P= .003). 

Ten-year survival rate was 32% (287 of 509) among patients who underwent transformation, and did not differ significantly between patients who received rituximab as induction or induction and maintenance therapy. 

The authors concluded, “these findings support the need to inform patients using rituximab nowadays that the risk of transformation is lower than it was before the introduction of rituximab.”


  1. Federico M, Barrigon MDC, Marcheselli L, et al. Rituximab and the risk of transformation of follicular lymphoma: a retrospective pooled analysis[published online July 4, 2018]. Lancet Haematol. doi: 10.1016/S2352-3026(18)30090-5