Navigating T-Cell-Directed Therapies in Transformed Follicular Lymphoma

T-cell-engaging therapies have revolutionized care for relapsed or refractory large B-cell lymphoma. Transformed follicular lymphoma (tFL) has had limited representation in CAR-T or bispecific antibody trials. Thus, outcomes in this subgroup are not well-described. Furthermore, trials that include aggressive disease transformed from indolent lymphomas often report collective outcomes rather than results for individual histologic subsets despite biologic heterogeneity; this limits interpretability of results. Despite these limitations, there are consistent signals that tFL responds well to T-cell-engaging therapies. tFL has a unique tumor microenvironment, but it is not clear if or how this contributes to the favorable outcomes. More robust data are available for CAR-T compared to bispecifics in this population and differences in responsiveness between the two therapies are difficult to ascertain. More research is needed to better understand biologic interaction of tFL with T-cell-engaging therapies and response to therapy to inform future clinical trials.