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

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.