Predictive Biomarkers and Personalized Medicine A Comparative Analysis of Prognostic Factor Models for Follicular Lymphoma Based on a Phase III Trial of CHOP– Rituximab versus CHOP þ Iodine—Tositumomab

Purpose: There is currently no consensus on optimal frontline therapy for patients with follicular lymphoma. We analyzed a phase III randomized intergroup trial comparing six cycles of CHOP-R (cyclophosphamide–Adriamycin–vincristine–prednisone (Oncovin)–rituximab) with six cycles of CHOP followed by iodine-131 tositumomab radioimmunotherapy (RIT) to assess whether any subsets benefited more from one treatment or the other, and to compare three prognostic models. ExperimentalDesign:Weconductedunivariate andmultivariate Cox regression analyses of 532patients enrolled on this trial and compared the prognostic value of the FLIPI (follicular lymphoma international prognostic index), FLIPI2, and LDH þ b2M (lactate dehydrogenase þ b2-microglobulin) models. Results: Outcomes were excellent, but not statistically different between the two study arms [5-year progression-free survival (PFS) of 60% with CHOP-R and 66% with CHOP-RIT (P 1⁄4 0.11); 5-year overall survival (OS) of 92% with CHOP-R and 86% with CHOP-RIT (P 1⁄4 0.08); overall response rate of 84% for both arms]. The only factor found to potentially predict the impact of treatment was serum b2M; among patients with normal b2M, CHOP-RIT patients had better PFS compared with CHOP-R patients, whereas among patients with high serum b2M, PFS by arm was similar (interaction P value 1⁄4 0.02). Conclusions: All three prognostic models (FLIPI, FLIPI2, and LDH þ b2M) predicted both PFS and OS well, though the LDH þ b2M model is easiest to apply and identified an especially poor risk subset. In an exploratory analysis using the latter model, there was a statistically significant trend suggesting that low-risk patients had superior observed PFS if treated with CHOP-RIT, whereas high-risk patients had a better PFS with CHOP-R. Clin Cancer Res; 19(23); 6624–32. 2013 AACR.