Identification of Patients with Follicular Lymphoma Patients at Risk of Failing Frontline Immunochemotherapy and Rituximab Maintenance
Authors: Garcia Recio Marta , Pérez-León Sandra , Bento Leyre , Salar Antonio , Sanchez-Gonzalez Blanca , Gines Jordi , Robredo Beatriz , García Lucia , Jiménez-Julià Sara Aida , Martínez-Serra Jordi , Sampol Antonia , Gutiérrez Antonio 
Published: October 2019

Abstract
Introduction :
Follicular lymphoma (FL) is an indolent non-Hodgkin lymphoma that represents 15-30% of all newly diagnosed lymphomas. It is characterized by a high rate of response followed by continuous relapses being considered incurable with standard immunochemotherapy regimens (Ardeshna et al. Lancet. 2003). The combination of immunochemotherapy and rituximab maintenance (Rm) improves progression free survival (PFS) when compared with a cohort without Rm (51% vs 35%) (Salles G. et al. ASH, 2017), being the standard for many centers. This improvement may have changed the risk assessment in FL. However, there is a need for identifying those patients with a poor prognosis with standard Rm-based therapy and candidates to receive alternative approaches using new drugs such as obinutuzumab with better reported results in this frontline setting (Gallium trial) (Marcus et al., 2017).
Methods :
From February-2002 to October-2016, all newly diagnosed FL patients with the intention to treat with immunochemotherapy and Rm where included. The participant centers were Son Espases University Hospital and Hospital del Mar of Barcelona. Clinical data were retrospectively collected from clinical histories and standard prognostic variables were evaluated at diagnosis including FLIPI and FLIPI-2. Another prognostic markers were defined: POD12 (progression of disease at 12 months), POD24 (progression of disease at 24 months) and POD30 (progression of disease at 30 months). The regimen effectiveness was evaluated based on the CT or PET/CT findings. Overall survival (OS) and PFS were determined from the date of the first cycle and they were estimated through Kaplan-Meier.
Results:
A total of 96 patients were included in the study with a median follow-up of 68 months. Main characteristics of the sample are shown in Tables 1. Briefly, median age was 61 years old, 88% where diagnosed in an advanced stage (III-IV), 36% and 38% presented with high risk (3-5) FLIPI and FLIPI2. Five-year OS and PFS was of 94% and 78% respectively. Univariate survival analysis proved that ECOG and response rate affected PFS and that stage and response influenced OS. In this analysis, no significant relation was found between the studied variables and POD12, POD24 or POD30 except beta2-microglobuline in POD30.
Conclusions: Frontline Rm significantly improves outcomes of FL patients. It seems that it is not possible to predict only with clinical variables which patients are in high risk of failure to a standard approach with immunochemotherapy followed by Rm. Additional prognostic factors such as molecular markers may help to identify these patients at risk of failure at the beginning of a first line of immunochemotherapy followed by Rm, and candidates for alternative approaches.

Disclosures
No relevant conflicts of interest to declare.