Follicular lymphoma grade 3A: aggressiveness and curability in an Asian cohort of 781 patients

Follicular lymphoma grade 3A (FL3A) is an uncommon subtype of FL with histology falling between FL grade 1/2 (FL1/2) and FL grade 3B (FL3B). The behavior of FL3A is currently debated, with some studies suggesting it may be potentially curable while others deem it incurable. However, the lack of large-scale studies with prolonged follow-up and changes in prognosis due to the use of rituximab (R) call for further investigation into the clinical course, prognosis, and treatment of FL3A in the R era. We conducted a follow-up for a median of 7.3 years (30% exceeded 10 years) on 104 FL3A cases who received R-CHOP/R-CHOP-like treatment. We compared the characteristics, clinical behavior, and prognosis of the FL3A group with control groups of DLBCL (n = 478), FL3B (n = 45), and FL1/2 (n = 154). Based on R-CHOP/like therapy, FL3A had similar outcomes to FL3B and DLBCL, with comparable 5-year and 10-year PFS and OS rates. Follow-up revealed that both FL3A and FL3B showed PFS platform 6 years after treatment initiation, while DLBCL had low recurrence rates (< 2%) after 5 years. FL1/2 showed persistent recurrence. No significant difference was observed in PFS among the four groups (p = 0.955) (Fig. 2A). Based on R-CHOP/R-CHOP-like regimen treatment, the OS of FL3A, FL3B and DLBCL manifested no statistically significant differences (p = 0.812), although FL3A appears to exhibit the poorest long-term survival in the curve, but FL1/2 showed better OS than the other three groups (p <0.001) (Fig. 2B). The period most at risk for recurrence was within the first year after initial treatment. Follicular Lymphoma International Prognostic Index (FLIPI) predicted PFS and OS for low-risk patients in FL3A, while FLIPI-2 was more effective in describing prognosis for high-risk patients in terms of PFS and OS. Based on treatment with R-CHOP/like, the prognosis of FL3A is comparable to that of FL3B and DLBCL. FL3A exhibits a PFS platform at 6 years post-initial treatment. FL3A had potential disease aggressiveness and curability.