Patterns of care, outcomes, and prognostics for transformed follicular lymphoma in the rituximab era

Abstract

Histologic transformation (HT) is the leading of death in follicular lymphoma (FL), yet outcomes remain poorly defined due to small cohorts and heterogenous definitions. To characterize outcomes and treatment patterns in the rituximab era we analyzed 344 patients with an initial biopsy-confirmed FL diagnosis between 2002 and 2022 who subsequently developed biopsy-confirmed HT in the Lymphoma Epidemiology of Outcomes (LEO) Consortium of Real-World Evidence (CReWE). Median age at HT was 64 (IQR 57-72). Initial treatment for HT (index therapy) included R-CHOP-like (n=154, 45%) and aggressive/salvage (n=85, 25%). The median event free survival (EFS) from HT was 9 months (95% CI, 7-11), and 2-year EFS was 30% (95% CI, 26%-36%). Median OS from HT was 4.9 years (95% CI, 4.0-7.5) with 2-year and 5-year OS estimates of 66% (95% CI, 61%-71%) and 49% (95% CI, 43%-56%), respectively.

Relapses after HT occurred in 60%. Relapse histology included DLBCL 70%, FL 15%, and HGBCL 12%. Treatment following relapse from index therapy was commonly aggressive/salvage (often incorporating ASCT/CAR-T) in 44%.

FLIPI (3-5), FL3A histology, IPI (4-5), ECOG >1, diagnosis to HT <2 years, HT within 2 years of immunochemotherapy (POD24), LDH, Hgb <10, prior anthracycline, and alkylator exposure were predicted inferior EFS. Age > 70 and HGBCL transformation portended inferior OS. An exploratory multivariable model, older age, HGBCL histology, prior anthracycline exposure, and shorter time to transformation predicted inferior OS. These data define the clinical course and treatment heterogeneity of tFL in a largely pre-CAR-T/bispecific era and provide context for future studies.