CD19 CAR-T Cell Therapy for Relapsed or Refractory Nodal and Gastrointestinal Follicular Lymphoma: Current Advances and Future Perspectives.

[PURPOSE OF REVIEW] Follicular lymphoma (FL) is the most common indolent B-cell lymphoma, yet primary gastrointestinal FL (GI-FL) remains poorly defined, and treatment of relapsed/refractory cases is controversial. This review aims to critically evaluate the role of CD19-directed chimeric antigen receptor (CAR) T-cell therapy in nodal and GI-FL, highlighting key clinical trials and the unique biological considerations of GI involvement.

[RECENT FINDINGS] Pivotal trials such as ZUMA-5, ELARA, and TRANSCEND FL have demonstrated high overall and complete response rates with durable progression-free survival in patients with relapsed/refractory FL. Liso-cel in particular has shown a favourable efficacy-toxicity balance, including in patients with transformed disease or progression within 24 months (POD24). However, data specific to GI-FL are scarce, and emerging evidence suggests that its microenvironment, immune checkpoint expression, and mutational profile may influence CAR-T responses differently from nodal FL. CD19 CAR-T therapy represents a major therapeutic advance for relapsed/refractory FL and holds promise for patients with advanced or high-risk GI-FL. Nonetheless, the rarity of GI-FL, limited dedicated clinical data, and challenges such as treatment-related toxicities, costs, and accessibility warrant further prospective studies. Integrating biomarker-based patient selection and GI-FL-specific trial designs will be crucial to optimise the application of CAR-T therapy in this distinct subtype.