Advanced Stage Follicular Lymphoma - Watch and Wait or Immunochemotherapy?
Authors: Pereira Dulcineia , Teixeira Carolina , Ramalheira Sofia , Rocha Patricia , Moreira Claudia , Rosinha Alina , Domingues Duarte , Amaral Natasha , Mesquita Edgar , Brito A , Viterbo Luisa , Oliveira Isabel , Domingues Nelson , Moreira Ilidia , Espirito-Santo Ana , Chacim Sergio , Leite Luis , Ferreira Isabel Cristina , Henrique Rui , Martins Angelo , Mariz Jose Mario 
Published: October 2019

Abstract
BACKGROUND: The outcome of patients with advanced stage Follicular Lymphoma (FL) has improved over the last decade, with the use of monoclonal antibodies (mAbs). The watch and wait approach (WW) in FL with low tumor burden was assumed when treatment options were limited and less effective than nowadays. In FL patients with indolent disease characterized by multiple relapses evolution, the therapeutic strategy should take into consideration the quality and duration of response and the impact on overall survival (OS) versus the risk of long-term toxicity.
AIMS: Evaluation of the impact of WW approach compared with chemotherapy (CT) in time to next treatment (TNT), progression-free survival (PFS) and OS.
METHODS: Retrospective study of 213 patients with FL, followed in a cancer care center between 2000-2012. Of these, 79 asymptomatic patients at diagnosis, with Ann Arbor stage III-IV were included and divided in 2 subgroups: 58 patients received the first-line treatment and 21 remained in surveillance. Tumor burden defined according to criteria of the Groupe d'Etude des Lymphomes Folliculaires (GELF). Survival analysis using the Kaplan-Meier method. Type of response defined according to NCCN criteria.
RESULTS: Median follow-up of 48 months (12-147). 41 of the 58 patients submitted to 1st line treatment [median age 57 years (38-72), 36.2% male], underwent CT regimen containing Rituximab. The majority of these patients presented with follicular pattern and histological grade 1/2 (89.7%), 34.5% had FLIPI ≥ 3 and 50 % high tumor burden (GELF), 15.5% bulky mass, 53.4% had > 4 nodal areas involved and 6.9% > 1 extranodal area involved. 52 of the treated patients (89.7%) achieved CR and in 4 progression occurred (6.9%). 50 patients (86.2%) were alive without evidence of disease at the end of study (86.2%). In the group of patients undergoing surveillance, 11 suffered disease progression (52.4%), of which 10 (47.6%) stayed alive without evidence of disease. The TNT was higher in patients undergoing 1st CT regimen, compared to patients on WW (median 1480.5 vs. 765 months, p <0.001) with significant impact on PFS (p <0.001) but not on OS. Analyzing the treated subgroup, the addition of immunotherapy resulted in better TNT and PFS compared to WW (p <0.001), without affecting the OS. In univariate Cox regression analysis, the number of areas and extranodal tumor burden (GELF) were independent predictors of PFS and TNT (p <0.05).
CONCLUSION: In asymptomatic patients with FL stage III-IV and high tumor burden, the CT especially when combined with immunotherapy, showed significant improvement on TNT and PFS compared to a WW approach, with no impact on OS. Despite a small sample group with retrospective data, our results are in agreement with the published literature.

Disclosures
No relevant conflicts of interest to declare.