Rituximab Is the Essential Treatment Modality That Underlies the Significant Improvement in Short and Long Term Outcome of Patients with Advanced Stage Follicular Lymphoma - A 10 Year Analysis of GLSG Trials.

Recent reports have shown a significant improvement of overall survival (OS) in patients with advanced stage follicular lymphoma (FL) over the last few decades. In order to identify the essential treatment modalities that underlie these observations two consecutive study generations of the German Low Grade Lymphoma Study Group (GLSG) covering a ten year period were analyzed for remission rates (RR), time to treatment failure (TTF) and OS. The analysis was adjusted for risk factors using the FLIPI, and type of primary induction therapy (including Rituximab or not). Between 1996 and 2005 complete data sets of 1332 patients with stage III or IV FL who were in need of therapy were collected. Therapy comprised prospective randomized comparisons of CHOP versus MCP in GLSG study ’96 (1996 – 2000) and CHOP versus R-CHOP in GLSG study ’00 (1996 – 2005). The entry criteria and the distribution of risk factors were identical in both study generations. The type of chemotherapy had limited impact on RR with CHOP being superior to MCP (86% versus 77%, p=0.0094) but no impact on TTF or OS. Patients treated in GLSG ’00 had a significantly better RR (94% versus 88%, odds ratio 0.47, p=0.0002), a longer TTF (median 48 months versus 32 months, relative risk 0.66, p<0.0001) and a longer OS (89% versus 78% at four years, relative risk 0.42, p<0.0001) as compared to patients of GLSG ’96. Multiple Cox regression analysis revealed Rituximab as being the determinant responsible for the differences in RR (adjusted odds ratio 0.45, p<0.0001) and TTF (adjusted relative risk 0.39, p<0.0001). With regard to OS, after adjusting for Rituximab as most relevant determinant (adjusted relative risk 0.44, p = 0.0064), the difference between the study generations still remained significant (adjusted relative risk 0.57, p = 0.0071). Hence, Rituximab is the essential treatment modality that underlies the improvement in short and long term outcome of patients with advanced stage FL. Most probably, more effective salvage therapy with Rituximab containing combinations account also for the additional improvement in OS.