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

in British journal of haematology by Ismael de la Iglesia-San Sebastián, Miguel López-Esteban, Mariana Bastos-Oreiro, Sara Fernández de Córdoba-Oñate, Maravillas Gutierrez, Diego Carbonell, Rebeca Bailén, Ignacio Gómez-Centurión, Paula Fernández-Caldas, Lucía Castilla, Javier Anguita, Mi Kwon, Ramón García-Sanz, Ismael Buño, Carolina Martínez-Laperche

TLDR

  • The study investigates CAR-cfDNA as a predictive biomarker of early relapse in ABCL patients treated with anti-CD19 CAR T-cells.
  • Higher levels of CAR-cfDNA on day +14 after infusion were associated with improved 6-month progression-free survival rates.
  • CAR-cfDNA may improve patient management and therapeutic strategies for ABCL patients undergoing CAR T-cell therapy.

Abstract

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.

Overview

  • The study investigates the use of circulating cell-free DNA (cfDNA) as a predictive biomarker of early relapse in aggressive B-cell lymphoma (ABCL) patients treated with anti-CD19 CAR T-cells.
  • The study analyzes CAR levels in peripheral blood and other clinical variables in 73 consecutive ABCL patients treated with anti-CD19 CAR T-cells.
  • The primary objective of the study is to identify a strong predictor of CAR T-cell therapy short-term outcomes in ABCL patients.

Comparative Analysis & Findings

  • The study found no correlation between genomic DNA and cfDNA.
  • Higher levels of CAR-cfDNA on day +14 after infusion were associated with improved 6-month progression-free survival rates (74.2% vs. 26%).
  • CAR-cfDNA could be a strong predictor of CAR T-cell therapy short-term outcomes.

Implications and Future Directions

  • The study suggests 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.
  • Future studies may need to explore the mechanistic basis of CAR-cfDNA as a predictive biomarker and its potential application in other types of cancer.
  • Establishing standardization for CAR-cfDNA analysis and correlation with other clinical variables is crucial for widespread adoption.
Read Full Article