Application of the mantle international prognostic index (MIPI) to patients with mantle cell lymphoma treated with fludarabine/cyclophosphamide: Results from a UK NCRI Lymphoma Group study

8555 Background: Mantle cell lymphoma (MCL) remains an incurable malignancy with conventional chemotherapeutic options with little randomised evidence to help direct therapy. The International Prognostic Index (IPI) for diffuse large cell lymphoma or Follicular Lymphoma International Prognostic Index (FLIPI) showed poor separation of survival curves in MCL patients. A new prognostic index (MIPI) based on age, performance status, lactate dehydrogenase (LDH), and leukocyte count was developed for patients with advanced stage MCL. Data from a randomised phase II NCRI trial designed to assess the effect of adding rituximab to an all oral chemotherapy regimen has been used to validate the MIPI. Methods: Patients with advanced stage, newly diagnosed MCL were randomised to receive either oral fludarabine 40mg/m2 and cyclophosphamide 250mg/m2 daily x 3 repeated every 28 days (FC) or FC with standard dose rituximab (375mg/m2 on day 1 of every cycle) (FCR). Patients could receive up to 8 cycles of treatment but no consolidation therapy was permitted. The primary outcome measures were response rate and the feasibility of a phase III randomised study. Results: 156 patients were randomised. Median age 64 (36–88) with a significant male predominance. With median follow up of 49 months for survivors the five year overall survival (OS) is 39%. 117 patients had complete data for calculating the simplified Mantle International Prognostic Index (MIPI) .There was equal distribution between the 3 risk groups (low risk 35%, intermediate risk 33% and high risk 31%). The median OS (months) for the 3 groups is; low not reached, intermediate 55.7 and high 20.4 (p of log rank test = 0.0048). However there is no difference between the 3 groups with regard to progression free survival (p=0.31). Conclusions: This large study of patients treated with an oral purine analogue combination confirms that the MIPI is predictive for OS. However MIPI does not discriminate for PFS suggesting that those patients with high scores have an inferior response to subsequent therapy post relapse after FC based therapy. No significant financial relationships to disclose.