The Emerging Role of CAR T-Cell Immunotherapy in Early Treatment of Large B-Cell Lymphoma

Anti-CD19 chimeric antigen receptor (CAR) T-cell immunotherapy has emerged as the new standard of care as a second-line treatment in refractory or early relapsing (R/R) large B-cell lymphoma (LBCL) patients. Given the notable incidence of LBCL in Switzerland, managing R/R disease remains a significant clinical challenge, especially in patients who do not respond to standard frontline chemoimmunotherapy. This review explores pivotal clinical trials that have driven the shift toward the earlier use of CAR T-cell immunotherapy in LBCL, highlighting its potential to improve clinical outcomes in primary refractory disease. Particular focus is given to the evolving role of CAR T-cell immunotherapy. Promising data suggest that its use in upfront lines of therapies might result in better disease control, even in high-risk, chemoresistant LBCL patients. Finally, we will discuss potential biological factors at the basis of the improved CAR T-cell activities observed when used in earlier lines of therapies. As CAR T-cell immunotherapies continue to be integrated into clinical practice, ongoing research and future trial data will be crucial for refining therapeutic protocols and optimizing patient outcomes. PEER REVIEWED ARTICLE **Peer reviewers:** Three anonymous peer reviewers Received on April 25, 2025; accepted after peer review on August 29, 2025; published online on September 26, 2025.