Differences in clinical characteristics and outcomes between patients with grade 3a and grades 1–2 follicular lymphoma: a real-world multicenter study

Background The difference between clinical characteristics and outcomes between follicular lymphoma grade 1–2 (FL1-2) and FL3a defined pathologically remains unclear, resulting in uncertainty how to treat FL3a. However, it may be crucial for clinicians to discriminate grade 3a and grade 1–2 for predicting prognosis and thus making treatment decisions. Methods We compared 1403 patients with FL1-2 and 765 patients with FL3a diagnosed between January 2000 and December 2020 from fifteen centers nationwide in China to describe differences in clinical characteristics and outcomes. Results Compared with FL1-2 patients, FL3a subgroup had a higher percentage of elderly patients ( P = 0.003), and relatively more FL3a patients presented with increased levels of LDH ( P < 0.0001) and higher Ki-67 indexs greater than 30% ( P < 0.001). More FL3a patients were treated with CHOP ± R ( P < 0.0001), and fewer were treated with the watchful-waiting approach ( P < 0.0001). The results showed a higher incidence of relapse among FL3a patients, in which more patients underwent histological transformation (HT) when compared to FL1-2 ( P = 0.003). 1470 (76.2%) patients of the entire cohort received R-CHOP therapy; survival analysis revealed that FL3a patients had a worse progression-free survival (PFS) rate than FL1-2 patients. Survival of FL3a patients with respect to FLIPI showed an inferior PFS in the intermediate and high-risk groups than FL1-2 patients. FL3a patients had a much worse prognosis than FL1-2 with or without progression of disease within 24 months (POD24). FL3a patients had higher likelihood of lymphoma-related death (LRD, P < 0.05), whereas the rates for non-LRD were comparable. Conclusion In conclusion, this study demonstrates a marked difference in clinical features and outcomes in FL3a patients compared with FL1-2 patients. The results highlight the need for applying therapeutic approaches distinct from FL1-2 when treating FL3a patients.