Dynamic ctDNA Monitoring: A Primary Tool Predictive of Response in a Patient on CAR-T Cell Therapy

Abstract

Introduction: Dynamic monitoring of circulating tumor DNA (ctDNA) offers a non-invasive method to track treatment response in malignancies. While well-established in solid tumors, its role in lymphomas, especially in predicting response to CAR-T cell therapy, remains underexplored-more so in the Indian context. This case highlights ctDNA as a potential predictive biomarker in relapsed/refractory DLBCL undergoing CAR-T therapy.

Case report: A 48-year-old male with transformed follicular lymphoma to DLBCL, refractory to R-CHOP and BR, was treated with anti-CD19 CAR-T cell therapy. Baseline ctDNA profiling from plasma revealed a TP53 p.E286K mutation at 1.3% VAF. Serial monitoring showed a decline to 0.4% at four weeks and complete clearance at eight weeks post-infusion, correlating with metabolic complete response on PET-CT. No co-occurring mutations were observed.

Discussion: This case illustrates how dynamic ctDNA profiling can reflect early molecular response, preceding radiological confirmation. Existing literature suggests that early ctDNA negativity post-CAR-T correlates with improved outcomes. This is the first reported Indian case employing a validated, homebrew NGS-based ctDNA assay to longitudinally track CAR-T response. Incorporating ctDNA-guided surveillance may refine response assessment and reduce unnecessary imaging, optimizing outcomes in resource-constrained settings.

Keywords: CAR19; DLBCL; PET CT; ctDNA.