Dynamic ctDNA Mutational Complexity in Patients with Melanoma Receiving Immunotherapy

Area of Science:

• Oncology
• Genomics
• Translational Research

Background:

• Circulating tumour DNA (ctDNA) analysis offers potential for improved cancer care, health equity, and translational research.
• An observational cohort study followed 29 advanced-stage cutaneous melanoma patients undergoing immunotherapy using ctDNA analysis.

Purpose of the Study:

• To investigate the utility of ctDNA analysis in tracking genomic changes during melanoma immunotherapy.
• To assess the technical validity and clinical correlations of ctDNA mutation detection.

Main Methods:

• Utilized a melanoma-specific ctDNA next-generation sequencing (NGS) panel, droplet digital polymerase chain reaction (ddPCR), and mass spectrometry.
• Analyzed longitudinal blood plasma samples from patients receiving immunotherapy in Aotearoa New Zealand.
• Compared ctDNA detection rates using standard versus cell-stabilizing collection tubes with delayed processing.

Main Results:

• Observed high dynamic mutational complexity, including multiple BRAF mutations and emerging sub-clonal mutations during therapy.
• Demonstrated high concordance between analysis methods and sample processing techniques (>90% for delayed processing).
• Found that undetectable ctDNA levels during treatment cycles were associated with durable clinical benefit (DCB).

Conclusions:

• Multiple ctDNA methods consistently identified complex longitudinal mutation patterns.
• Results support the expanded clinical trial of ctDNA analysis in various oncology settings.
• ctDNA analysis shows promise for guiding cancer treatment and monitoring response.