Chimeric antigen receptor copies in cell‐free DNA predict relapse in aggressive B‐cell lymphoma patients treated with CAR T‐cell therapy

Summary Chimeric antigen receptor (CAR) T‐cell therapy has emerged as a transformative treatment for aggressive B‐cell lymphomas (ABCL), However, about half of patients relapse, most of them early. This study investigates the detection of CAR copies in circulating cell‐free DNA (cfDNA) as a potential predictive biomarker of early relapse (<6 months) to improve patient management. In this research, we have consecutively selected 73 ABCL patients treated with anti‐CD19 CAR T‐cells, analysing CAR levels in peripheral blood and other clinical variables. Our results indicate that no correlation is present between genomic DNA and cfDNA; moreover, higher levels of CAR ‐cfDNA on day +14 after infusion (0.44 vs. 0.07; p = 0.019) are associated with improved 6‐month progression‐free survival rates (74.2% vs. 26%. p < 0.01), suggesting that CAR ‐cfDNA could be a strong predictor of CAR T‐cell therapy short‐term outcomes. These findings underscore the potential of integrating CAR ‐cfDNA analysis into routine clinical practice to enhance the prognostic accuracy and therapeutic strategies for ABCL patients undergoing CAR T‐cell therapy.