IBCL-333 Follicular Lymphoma (FL) 3B Patients Have a Superior Risk of an Aggressive Disease at First Event Compared to Those With FL1–3A Treated With Front-Line R-CHOP

Context: FL3B presents a distinctly adverse prognosis compared with the lower-grade FL. Accumulating evidence suggests that FL3B resembles diffuse large B-cell lymphoma (DLBCL) rather than FL1–3A. Accordingly, R-CHOP is the mainstay therapy for FL3B but fails to cure half of patients (pts), suggesting a biological dichotomy with clinical implications. However, whether composite FL3B with DLBCL (FL3Bc) rather than uniform FL3B (FL3Bu) is responsible for a worse prognosis remains unclear. Objective: We compared the outcomes of R-CHOP–treated FL1–3B pts and clarified the phenotypic distinction of FL3B subpopulations. Patients and Methods: We evaluated 303 newly diagnosed FL1–3B pts who received front-line R-CHOP (FL1–2 n=122, FL3A n=114, FL3B n=67 [FL3Bu n=33 and FL3Bc n=36]) and were prospectively enrolled into the University of Iowa/Mayo Clinic SPORE Molecular Epidemiology Resource cohort from 2002 to 2021. Event-free survival (EFS) was calculated from diagnosis until progression/relapse, retreatment, or death. Early progression was defined as failing to achieve EFS at 24 months (EFS24). Subtype was abstracted at first event. Results: Baseline characteristics were broadly similar across FL subtypes, with FL3A pts having lower LDH (28%, p=0.01) and FL3B pts having less bone marrow involvement (23%, p=0.01). Among FL3B pts, 36 (54%) had FL3Bc with similar features to FL3Bu (n=31, 46%), except for higher LDH levels (48% vs 38%, p=0.01). After a median follow-up of 119 months, the overall EFS was 160 months. Compared with FL1–2, patients with FL3A (HR 0.74, 95% CI 0.51–1.08) and FL3B (HR 0.59, 95% CI 0.36–0.97) had superior EFS. Early progression occurred more frequently in FL1–2 pts (33%) than in those with FL3A (17%) and FL3B (22%, p=0.02); however, this did not translate to a survival disadvantage (p=0.77). FL1–3A pts predominantly had indolent disease (FL1–3A) at first event, whereas aggressive disease (FL3B or DLBCL) was the most common subtype at progression in pts with FL3B, irrespective of the initial composite disease. Conclusions: FL3B pts treated with R-CHOP have improved EFS but are more likely to have an aggressive subtype at progression compared with pts with FL1–2 and FL3A treated with R-CHOP. Larger studies are warranted.