Clinical Outcomes of Transformed Follicular Lymphoma with CAR T-Cell Therapy: A US Multicenter Real-World Analysis

• Published in: Blood 2024-11, Vol.144 (Supplement 1), p.525-525
• Main Authors: Cortese, MD, MPH, Matthew J., Herr, Megan M, Nair, Nisha, Romancik, Jason, Grover, Natalie, Bhansali, Rahul S, Thomas, Colin, Moyo, Tamara K, Kenkre, Vaishalee P, Ollila, Thomas, Hess, Brian, Fitzgerald, Lindsey, Shouse, Geoffrey, Matasar, Matthew, Annunzio, Kaitlin, Davis, James A, Jesme, Christy, Pelcovits, Ari, Melody, Megan, Moreira, Jonathan, Lin, Adam Yuh, Ma, Shuo, Winter, Jane N, Niu, Alex, Danilov, Alexey V., Shah, Nirav N., Stephens, Deborah M., Cohen, Jonathon B., Gordon, Leo I., Barta, Stefan K., Epperla, Narendranath, Karmali, Reem
• Format: Article
• Language: English
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood-2024-212106

Background: Chimeric Antigen Receptor T-cell therapy (CART) has substantially improved outcomes for patients (pts) with relapsed/refractory (R/R) aggressive B-cell lymphomas, with impressive overall response rates (ORR) and 3+ year complete remission rates (CRR) ranging from 30-40%. As a result, CART is now FDA-approved for the treatment of R/R diffuse large B-cell lymphoma (DLBCL) and transformed follicular lymphoma (tFL). In registrational clinical trials (e.g. ZUMA-1/ZUMA-7, TRANSCEND NHL 001/TRANSFORM, JULIET/BELINDA) these biologically distinct lymphomas were included and analyzed together. As such, the prognostic impact of tFL histology with respect to CART outcomes has remained largely unknown and warrants clarification. Methods: We performed a retrospective cohort study of pts with de novo DLBCL (dnDLBCL) and tFL treated with CD19-directed CART from 2015 to 2024 across 14 US academic institutions, with follow-up through June 30, 2024. All cases were pathologically-confirmed locally, with dnDLBCL defined as DLBCL without clinicopathologic evidence of an antecedent or concurrent low-grade lymphoma and tFL as DLBCL arising from an antecedent classical follicular lymphoma. Cases were also sub-classified by “double hit” lymphoma (DHL) or “double expressor” lymphoma (DEL) status. Differences in patient, clinical, and treatment characteristics were examined using chi-square and Wilcoxon rank sum tests. Overall survival (OS) and progression-free survival (PFS) were estimated using Kaplan-Meier survival curves, and de novo DLBCL and tFL pts were compared using log-rank tests. Cox proportional hazards models were used for multivariable analyses. Results: Of the 691 pts included in this analysis, 552 had dnDLBCL (88 with DHL, 90 with DEL) and 139 had tFL (27 with DHL, 22 with DEL). There was no significant difference between dnDLBCL and tFL cohorts in median age (60, range 21-85 years), gender, race, ECOG performance status, IPI score, primary refractory disease (14 vs 16%) or early relapse