Translational insights into the genetics and immunobiology of relapsed/refractory follicular lymphoma
- PMID: 38761562
- DOI: 10.1016/j.leukres.2024.107519
Translational insights into the genetics and immunobiology of relapsed/refractory follicular lymphoma
Abstract
Although follicular lymphoma (FL) is traditionally classified as an indolent subtype of B cell non-Hodgkin lymphoma, clinical trajectories are often diverse based on unique disease biology, and many patients will eventually experience relapse of their disease. Furthermore, progression of disease within 24 months is associated with increased mortality rates for FL. In the last five years, we have witnessed an upsurge in the commercial availability of targeted therapies for relapsed/refractory (R/R) FL, including chimeric antigen receptor-T (CAR-T) products, bispecific T cell engagers (BiTEs), epigenetic modifier therapies, and next-generation Bruton tyrosine kinase (BTK) inhibitors. Furthermore, clinical trial options have increased tremendously and now include combinatorial strategies that exert synergy against malignant germinal center B cells. Here, we provide a 2024 update of novel therapeutic agents whose development has been informed by recent advances in the genetics and immunobiology of R/R FL. Specifically, we emphasize high-value targeted therapeutics, including anti-CD3 x anti-CD20 BiTEs and adoptive T cell therapies. We discuss prospects on selection and sequencing of BiTEs and CAR-T therapies for patients with R/R FL. We underscore the principles of FL pathobiology that are paving way for future drug discovery and shed insight into therapeutic targeting within nodal basins based on our increasing understanding of the FL microenvironment. Finally, we summarize how a greater knowledge of FL immunobiology can inform risk stratification and therapy selection on a personalized basis for R/R FL in 2025.
Keywords: Bispecific antibodies; CAR-T cells; Follicular lymphoma; Novel therapies.
Copyright © 2024 Elsevier Ltd. All rights reserved.
Conflict of interest statement
Declaration of Competing Interest SAP served on the COMMANDS advisory board and the Acute Myeloid Leukemia advisory board for Bristol Myers Squibb and served on the Multiple Myeloma advisory board for Pfizer. All other authors have no disclosures.
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