Clinical implications of ctDNA-based minimal residual disease detection in newly diagnosed peripheral T-cell lymphoma: a single-center cohort study

Circulating tumor DNA (ctDNA) has been recognized as a promising tumor-specific biomarker, but its molecular features in peripheral T cell lymphoma (PTCL) have not been well explored. We investigated the translational significance of liquid biopsy in a uniformly treated PTCL cohort (N=64). Our study found that pretreatment ctDNA burden was strongly associated with clinical risk factors and identified as a superior predictor of progression-free survival and overall survival. Although 46.9% of patients achieved complete response at the end of therapy (EOT), only 25.9% achieved negative minimal residual disease (MRDend-) and demonstrated superior prognosis. These findings suggests that MRD status at EOT may be a critical factor in disease progression and recurrence for PTCL patients. Additionally, the most frequently altered genes were identified as TET2 (6.7%), DNMT3A (48.5%), RHOA (27.3%), and TP53 (15.2%), which were not cleared by first-line CHOP-like regimens. Most importantly, clonal evolution was displayed during induction therapy and follow-up across all histological subtypes of PTCL patients.These findings support that EOT MRD status could serve as an important prognostic marker for PTCL patients and clear the direction of exploration and selection the new drugs particularly targeted to TET2/DNMT3A/RHOA mutation integrating with conventional treatments for PTCL patients.