Feasibility of Longitudinal Circulating Tumor DNA (ctDNA) Assessment in Patients with Peripheral and Cutaneous T-Cell Lymphomas

T-cell lymphomas are a heterogeneous group of mature T-cell neoplasms. Outcomes of majority of peripheral T-cell lymphoma (PTCL) and advanced stage cutaneous T-cell lymphomas (CTCL) are poor. The value of ctDNA as a prognostic marker of chemosensitivity and disease-free survival has been validated in aggressive B-cell lymphomas but remain unclear in PTCL/CTCL and can be a useful tool for disease risk stratification and monitoring of treatment.

We performed a retrospective review of PTCL and CTCL patients treated at our center between April 2022 and June 2024; plasma samples were analyzed using a tumor-informed ctDNA assay as part of clinical care during diagnosis, treatment, and surveillance. Whole exome sequencing was performed on tumor tissue and matched normal blood samples to identify up to 16 patient- and tumor-specific, somatic single nucleotide variants using a clinically validated, tumor-informed mPCR NGS assay (Signatera^TM). These variants were monitored in patients' subsequent plasma samples.

A total of 75 plasma samples were analyzed from 10 patients with PTCL/CTCL; lymphoblastic lymphoma (n=2), enteropathy associated T-cell lymphoma (n=2), ALK+ anaplastic large T-cell lymphoma (n=1), PTCL-NOS (n=1), angioimmunoblastic T-cell lymphoma (n=1), hepatosplenic T-cell lymphoma (n=1), and CTCL (n=2). After a median duration of follow-up of 6 (2-24) months, 7 (70%) patients remained alive. In patients with PTCL (n-8), persistence of ctDNA was strongly associated with disease progression and death (relative risk=6; 95% CI=1-35; p=0.04). In 5 patients with PTCL, ctDNA negativity showed 100% concordance with negative PET-CT results.

Our results, albeit with small numbers, suggest that ctDNA is strongly associated with clinical outcomes in patients with PTCL; ctDNA may serve as a useful tool to monitor and prognosticate patients with PTCL when validated in a large cohort of patients.

William:ADC Therapeutics: Consultancy; BMS: Consultancy; Genmab: Consultancy; Morphosys: Consultancy; Guidepoint Global: Consultancy. Efebera:Takeda, Janssen, Akcea Therapeutics, Alnylum: Speakers Bureau; Oncopeptides, Sanofi, Janssen Oncology, Pfizer: Consultancy; Takeda, Oncopeptides, Alnylam, Sanofi, GlaxoSmithKline, ORCA Therapeutics, Bristol Myers Squibb/Celgene, Pharmacyclics through Alliance and AFT: Research Funding.