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A COMPARATIVE ANALYSIS OF HISTOLOGIC TRANSFORMATION OF FOLLICULAR LYMPHOMA AT DIAGNOSIS (COMPOSITE LYMPHOMA) AND SEQUENTIALLY TRANSFORMED FOLLICULAR LYMPHOMA
Abstract   Peer reviewed

A COMPARATIVE ANALYSIS OF HISTOLOGIC TRANSFORMATION OF FOLLICULAR LYMPHOMA AT DIAGNOSIS (COMPOSITE LYMPHOMA) AND SEQUENTIALLY TRANSFORMED FOLLICULAR LYMPHOMA

C. Casulo, M. C. Larson, J. R. Day, U. Durani, M. Tsang, D. Chihara, W. R. Burack, M. Holets, J. W. Friedberg, C. K. Gribben, …
Hematological oncology, Vol.43(S3)
06/2025
DOI: 10.1002/hon.70093_29

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Abstract

Introduction: Histologic transformation (HT) of follicular lymphoma (FL) may develop sequentially (sHT) following initial diagnosis of indolent disease or coexist concurrently at diagnosis as composite lymphoma (cHT). Clinical and tumor-based factors may predict the risk of sHT, and outcomes differ compared to de novo diffuse large B-cell lymphoma (DLBCL). Data are limited for predicting individual risk and outcomes in the setting of concurrent transformation. To address this, we assessed the clinical features and outcomes among patients (pts) with sHT versus cHT prospectively enrolled in the Lymphoma Epidemiology of Outcomes and its antecedent Molecular Epidemiology Resource cohort. Methods: Eligible pts were diagnosed between 2002 and 2022, had biopsy proven FL 1–3A at diagnosis with a subsequent biopsy (at least 3 months after the first biopsy) showing HT to an aggressive lymphoma (DLBCL or high-grade B cell lymphoma (HGBCL)) [sHT] or biopsy proven FL with components of aggressive lymphoma [cHT]. Endpoints included event-free survival (EFS), overall survival (OS), and lymphoma-specific survival (LSS) from treatment initiation immediately following HT. Results: We identified 424 pts with cHT (n = 236) and sHT (n = 188). In the cHT group, median age was 62 (23–91), 57% were male, 95% had DLBCL/FL and 5% HGBCL/FL. 70% had advanced disease and 32% IPI 3–5. Treatment for cHT was R-CHOP (83%), R-EPOCH (3%), other immunochemotherapy (IC) (5%), other systemic (5%), and non-systemic therapy (5%). Pts at time of sHT were slightly older than cHT (median age 65 (24–90)), 52% were male, 61% had DLBCL, 24% DLBCL/FL, 14% HGBCL, and 2% HGBCL/FL. 88% had advanced disease and 36% IPI 3–5. 70% had prior systemic therapy of whom 37% had prior IC; 24% had POD24 to first line IC. Treatment for sHT was R-CHOP (51%), R-EPOCH (2%), other IC (2%), other systemic (32%), and non-systemic (2%). Among the subset of IC treated pts (212 cHT, 120 sHT), 5 years OS was 81% (95% CI 76–87) for cHT, significantly higher than sHT pts without prior systemic (72%, p = 0.02) and with prior systemic therapy (49%, p < 0.001). Lymphoma was the leading cause of death in all groups, with 5 years LSS of 84% for cHT (95% CI 80–90) versus 54% for sHT (95% CI 47–63), p < 0.001. We observed similar findings for EFS, 5 years EFS was 66% (cHT) versus 40% in pts with sHT and no prior systemic therapy, p = 0.003. 5 years EFS was lowest in sHT pts having prior systemic therapy, 32%, p < 0.001. Treatment patterns and predictors of outcome will be presented at the meeting. Conclusions: We present outcomes of the largest cohort of sequential and composite transformed FL from a contemporary, multicenter U.S. prospective study, identifying that cHT and sHT are different. sHT is an unmet need, with inferior OS and EFS, particularly in pts with prior systemic therapy. Our findings suggest distinct behavior between sHT and cHT and warrants further study of the molecular underpinnings driving this clinical phenotype for more personalized treatment.

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