Revalidation of the Flipi Score in the Era of Immunotherapy.
Authors: Stemmelin German , Doti Carlos , Shanley Claudia , Ceresetto Jose , Rabinovich Oscar , Vicente Angeles , Vukovic Matias , Cazap Nicolas , Preiti Vereonica , Palmer Silvina , Vitriu Adriana , Bullorsky Eduardo 
Published: November 2019

Abstract
The FLIPI prognosis score for follicular lymphoma (FL) was developed based on cases diagnosed between 1985 and 1992, and treated with different schemes that did not include rituximab (R). In the present study, we report the evolution of all FL treated in a single institution through the last decade and analize whether FLIPI mantains its effectiveness to identify different risk groups within patients treated with the new therapeutic alternatives available.
Material and Methods: We identified sixty two patients with diagnosis of grade I-II-IIIa FL. Patients characteristics: median age 57.5 yr (r, 30–80); 36 males; 63% stages III–IV, and 37% with bone marrow infiltration at the time of diagnosis. Thirty eight percent had a low risk by FLIPI, 34% had an intermediate risk and 27.4% had a high risk. In 19 pts (30.6%) the initial decision was “watch and wait” but 82% received a form of treatment at some point. R was used in 36 pts (58%) with some of the following regimes: chemotherapy (chemo) + R and/or R as consolidation therapy and/or R as monotherapy and/or R as maintenance therapy. Of all prescribed treatments (excluding R as monotherapy and/or maintenance treatment), 52.8% were chemo alone, 20.2% chemo + R, 21.3% radiotherapy and 5.6% received a bone marrow transplant.
Results: we considered the analysis of overall survival (OS) the most appropiate approach, since most treatments were seeking the control of the FL, and not the complete remission or cure. The follow up median time was 53.2 months ± 34.8 1SD. The 5-yr OS for the 62 pts was 81.8% ± 11.3 CI 95%. The 5-yr OS for those with a low, intermediate and high risk FLIPI was 100% −5, 84.2% ± 21 and 52% ±26.2, respectively. The difference in 5-yr OS was statistically significant between low and high risk, intermediate and high risk, but failed to prove a significant difference between low and intermediate risk. Among the different risk factors tested in a univariate analysis only age ≥ < 60 yr old demonstrated a significant difference, 60.7% vs 90%, respectively.
Conclusions:
The 5-yr OS in our series is higher than the one described in the original FLIPI study (Blood2004; 104:1258–65) which was 81.8% vs 71% for the whole group; 90% vs 78.1% for pts <60 yr old; 60.7% vs 57.7% for ≥ 60 yr old; 100% vs 90.6% for low FLIPI and 84.2% vs 77.6% for intermediate FLIPI. The only group that failed to prove an improvement was the high risk FLIPI with 52% vs 52.5%. The impact of novel therapies was more evident in patients with a low or intermediate FLIPI and was even more evident in patients younger than 60 yr old. According to our results, FLIPI maintains its effectiveness in differentiating two risk groups, i.e., low-intermediate vs high. We believe that the OS curves will probably continue to improve as the treatments that are considered today as the most effective ones, were just included in our series in the last three years.