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

Area of Science:

• Oncology
• Molecular Diagnostics
• Immunotherapy

Background:

• Circulating tumor DNA (ctDNA) monitoring is a non-invasive tool for tracking treatment response in cancers.
• Its utility in lymphomas, particularly predicting CAR-T cell therapy outcomes, is less understood, especially in India.
• This case explores ctDNA's predictive role in relapsed/refractory diffuse large B-cell lymphoma (DLBCL) treated with CAR-T therapy.

Observation:

• A patient with transformed follicular lymphoma to DLBCL, refractory to standard treatments, received anti-CD19 CAR-T cell therapy.
• Baseline ctDNA analysis detected a TP53 mutation.
• Serial ctDNA monitoring showed a significant decline and eventual clearance of the mutation post-therapy, aligning with radiological response.

Findings:

• Dynamic ctDNA profiling accurately reflected early molecular response to CAR-T therapy, preceding imaging confirmation.
• Early ctDNA negativity post-CAR-T therapy is associated with improved patient outcomes.
• This is the first Indian case study using a validated NGS-based ctDNA assay for longitudinal CAR-T response tracking.

Implications:

• ctDNA-guided surveillance can refine response assessment in DLBCL patients undergoing CAR-T therapy.
• This approach may help reduce the need for extensive radiological imaging, optimizing care in resource-limited settings.
• ctDNA serves as a promising predictive biomarker for CAR-T cell therapy efficacy in lymphomas.