The Impact Of Prior Exposure To Rituximab On Autologous Stem Cell Transplantation In Patients With Follicular And Transformed Lymphoma

Introduction: Addition of rituximab to chemotherapy (CT) for follicular lymphoma (FL) has been shown to improve many outcome parameters. Often, high-dose therapy is followed by autologous stem-cell transplantation (ASCT) after 1, 2 or more relapses. Kang et al. (BMT (2007) 40, 973) investigated whether prior exposure to rituximab had any influence on a subsequent ASCT and found no differences in the outcomes analyzed. However, there has been evidence suggesting that that such prior exposure may alter the phenotype of these tumour cells so that they no longer express CD20, and thus potentially altering their behaviour. Methods: We performed a retrospective review on all patients having received an ASCT at the Ottawa Hospital with an initial diagnosis of FL. They were grouped into four categories according to their prior exposure to or lack of prior exposure to rituximab and according to their pre-ASCT diagnosis, non-transformed FL (FL-NT) vs. transformed (FL-T). Results: 259 patients who underwent an autoHSCT for FL were divided into 4 groups: 184 FL non-transformed (FL-NT) (31 patients received rituximab and 153 did not), and 75 FL-transformed (FL-T) (24 patients received rituximab and 51 did not). The 5-year progression-free survivals (PFS) were 61.2% and 27.6%, respectively (p<0.0001) and the overall survivals (OS) were 72.5% and 39.3%, respectively, (p<0.0001). In the FL-NT group, no differences existed in PFS or OS between FL-NT rituximab-naïve and rituximab-treated patients (5-year PFS 61% vs. 64%, p=0.69; 5-year OS 73% vs. 68%, p=0.80). Within the FL-T group, the subsequent 5-year PFS of the rituximab-naive vs. pre-treated groups were 22% and 55% (p =0.20), respectively, and the 5-year OS were 36% and 51% (p=0.39), respectively. Prior exposure to R had a positive effect (Hazard Ratio (HR): 0.44, 95% CI 0.20-0.97, p=0.04) on PFS and OS (HR: 0.5, 95% CI 0.21-1.18, p=0.11). Pre-treatment with rituximab in FL-NT prior to ASCT does not adversely impact ASCT outcomes. There is a suggestion of an increase in the number of patients with FL-T being transplanted in the post-rituximab era and as expected, the FL-T had a poorer outcome than the FL-NT patients. However, prior exposure to rituximab appeared to demonstrate a trend toward an improved OS within the FL-T group. In summary, previous rituximab exposure may be associated with an increased rate of transformation, leading to the poorer outcome of patients originally diagnosed with FL-NT.