CD19-directed chimeric antigen receptor T-cell therapy for relapsed or refractory diffuse large B-cell lymphoma: lessons learned from clinical trials and real world evidence

CD19-directed Chimeric Antigen Receptor T-Cell therapy has revolutionized treatment for relapsed or refractory diffuse large B-cell lymphoma (R/R DLBCL). Since the approval of axicabtagene ciloleucel, tisagenlecleucel and lisocabtagene maraleucel—CAR-T has offered high response rates and durable remissions for patients with limited options. Real-world data support its curative potential in 40–50% of patients. However, challenges remain, including toxicity management, individualized manufacturing, logistical complexity and access barriers. Over seven years of clinical experience have led to streamlined manufacturing and improved strategies for managing toxicities such as cytokine release syndrome and immune effector cell-associated neurotoxicity syndrome. These advances have expanded access and optimized delivery. Ongoing refinements in patient selection, and toxicity mitigation continue to improve outcomes. This review consolidates pivotal trial and real-world findings, addressing non-conforming products, outpatient administration, access barriers, and future directions. Emerging innovations in next-generation therapies and access strategies offer a roadmap for continued clinical and research progress.