Remission Assessment by Circulating Tumor DNA in Large B-Cell Lymphoma.

Area of Science:

• Hematology
• Oncology
• Molecular Diagnostics

Background:

• Large B-cell lymphomas (LBCL) are curable, but residual disease post-therapy leads to progression.
• Current remission determination methods may not accurately predict patient outcomes.

Purpose of the Study:

• To evaluate the prognostic utility of ultrasensitive circulating tumor DNA (ctDNA) detection for minimal residual disease (MRD) in LBCL patients.
• To compare ctDNA-MRD status with conventional radiographic response criteria for predicting progression-free survival (PFS).

Main Methods:

• Integrated data from five prospective studies of frontline anthracycline-based chemotherapy in LBCL patients.
• Monitored tumor-specific phased variants from pretreatment samples in serial plasma specimens.
• Assessed ctDNA as MRD and compared its prognostic value to conventional response criteria for PFS.

Main Results:

• In 137 patients, detectable ctDNA rates decreased during therapy, with 78% achieving undetectable ctDNA by end of treatment.
• Patients with undetectable ctDNA after 2 cycles (96%) and at end of therapy (97%) had significantly better 2-year PFS than those with detectable ctDNA (67% and 29%, respectively).
• ctDNA-MRD status at end of therapy demonstrated superior prognostic utility compared to PET scan response criteria.

Conclusions:

• Ultrasensitive ctDNA detection for MRD after frontline LBCL therapy is a more powerful prognostic indicator than conventional radiographic response.
• Refining remission definitions using ctDNA-MRD may enhance clinical and psychological outcomes for LBCL patients.