Pb2091: influence of histological grade in clinical characteristics and long-term outcome of folicular lymphoma

Background: Despite extensive studies over the years, follicular lymphoma grade 3A (FL G3A) remains poorly characterized in terms of long-term outcome and optimal clinical approach. While FL grades 1 and 2 and 3B present differential traits and disease course (grades 1 and 2 behave as a slowly progressive disease with multiple relapses after different lines of treatment, and grade 2B resembles a diffuse large B-cell lymphoma), studies disagree weather G3A FL behaves similarly to low grade FL or if it presents a more aggressive clinical course. Aims: To analyse the impact of histological G3A in clinical characteristics and evolution of patients with FL in comparison with grades 1 and 2 FL. Methods: This is a retrospective analysis of a cohort of 241 patients with newly diagnosed FL between the years 2006 and 2020. Data regarding histological grade was unavailable in 10 patients. Patients with FL grade 3B (18) and patients with a single extranodal area affected (13) were excluded from the analysis. Finally, a total of 200 patients were included in the study. SPSS® was used for all statistical analysis. Chi square test was used for comparisons between groups and Kaplan-Meier method and log rank test for the survival analysis. Results: 173 patients (86.5%) were diagnosed with low-grade FL (G1-2 FL), and 27 (13.5%) with G3A FL. Median age at diagnosis was 66 years and it did not differ in both groups. 52% of the patients were female. 25.7% of the patients presented a high-risk FLIPI2 in the G1-2 FL group vs 45% in the G3A FL group, although this difference was not statistically significant (p=0.1). Lymphoma characteristics at diagnosis were in the main similar in both groups: Ann Arbor stage, bone marrow infiltration, extranodal involvement and presence of bulky mass did not differ in both groups. However, G3A FL patients more frequently presented elevated LDH at diagnosis (27 vs 52%; p=0.027) and B symptoms (25 vs 61%; p=0.001). Regarding the evolution, 157 patients required treatment at any point during the evolution, 80% of patients with G1-2 FL and 89% of patients with G3A FL (p=0.26). First line therapy was most commonly immune-chemotherapy, the most used regimens were R-CHOP (59.2%) and bendamustine-rituximab (24.8%). 67.5% of patients achieved complete response (CR), and 87% partial response or better to first line therapy; the proportion was similar in both groups. Relapses occurred in 40% of the patients who received a first-line treatment. There were no differences in percentage of relapses (35.5% for G1-2 FL vs 42.3% por G3A FL) or POD depending on histological grade. With a median follow-up of 58 months, there were no differences in Progression Free Survival (Estimated 3-year PFS G3A 62% vs G1-2 68%; p=0.75) or Overall Survival (Estimated 5-year OS G3A 95% vs G1-2: 91%; p=0.38) (Figure 1). G3A FL showed in PFS curve no relapses after 6 years. 21 patients transformed into a high-grade lymphoma and 14 developed a second neoplasm during follow-up. Finally, 35 patients died during this time, 13 due to lymphoma progression and 27 due to non-disease related causes, with no difference between groups. Image:Summary/Conclusion: G3A follicular lymphoma presents mostly similar characteristics and outcome as low-grade follicular lymphoma. However, it may present some more aggressive traits, such as more frequent B symptoms and elevated LDH. Our results indicate similar long-term outcomes in terms of progression-free survival and overall survival in grades 1-2 and 3A. No relapses were observed in G3AFL group after 6 years. These findings should be confirmed in prospective studies.