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Novel non-invasive biomarker ctDNA shows value in CNS lymphoma

Presented by
Dr Jurik Mutter, University Medical Center Freiburg, Germany
ASH 2021
Circulating tumour DNA (ctDNA) was associated with progression-free survival (PFS) and overall survival (OS) in patients with central nervous system (CNS) lymphoma. Moreover, the ultrasensitive and robust detection of ctDNA in patients with different disease severity suggested accurate reflection of tumour burden, thereby supporting the potential of this biomarker as a decision-making tool in clinical practice [1].

Selecting patients at high risk for treatment failure is an unmet need in the management of patients with CNS lymphoma. Moreover, the invasive neurosurgical methods that are currently used for the diagnosis of this disease carry risks and require an adequate fitness level of the patient. ctDNA is a promising, non-invasive biomarker for patients with systemic lymphoma. Dr Jurik Mutter (University Medical Center Freiburg, Germany) and colleagues assessed the potential of ctDNA in CNS lymphoma through Cancer Personalised Profiling by Deep Sequencing (CAPP-Seq) and Phased Variant Enrichment and Detection Sequencing (PhasED-Seq).

In total, 794 distinct genetic regions were analysed, originating from plasma samples, tumour biopsies, and cerebrospinal fluid (CSF) specimens from 92 patients with CNS lymphoma and 44 patients with other brain cancers or inflammatory cerebral diseases. Radiological measures of tumour burden were correlated with ctDNA concentrations. Also, ctDNA concentrations were assessed for their link to clinical outcomes.

The results showed that concentrations of ctDNA were significantly correlated to MRI measures of tumour volumes (r=0.53; P<0.0001). Moreover, a positive pre-treatment ctDNA status was predictive of worse PFS (HR 4.6; P<0.0001) and OS (HR 6.1; P=0.002). Similarly, ctDNA positivity during induction therapy was related to worse PFS (HR 6.2; P=0.0002) and OS (P=0.004) outcomes. Furthermore, a novel machine learning classifier analysed 207 specimens of patients with and without CNS lymphoma. The research team observed a specificity of 100% and a sensitivity of 57% for CSF samples in diagnosing CNS lymphoma through ctDNA measures, reflecting that a substantial proportion of patients may avoid invasive diagnostic procedures.

The authors argued that ctDNA may be an important decision-making tool in the management of patients with CNS lymphoma in the future.

  1. Mutter JA, et al. Profiling of Circulating Tumor DNA for Noninvasive Disease Detection, Risk Stratification, and MRD Monitoring in Patients with CNS Lymphoma. Abstract 6, ASH 2021 Annual Meeting, 11‚Äď14 December.


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