ctDNA and beyond to serve immunotherapy

Recent advancements have reaffirmed the significance of liquid biopsy in the management of advanced solid tumors, although further prospective research is still required. Historically, the treatment of these tumors has posed a considerable challenge due to the limited therapeutic options, such as chemotherapy and radiotherapy. The emergence of personalized medicine, particularly targeted therapies and immune-checkpoint inhibitors (ICIs), has notably enhanced patient outcomes. For those who do not respond to targeted treatments, ICIs, either alone or combined with cytotoxic agents, have been employed.

Currently, the decision to administer ICIs relies on immunohistochemical or immunocytochemical assessments of PD-L1 expression in tissue samples. However, as tissue samples are often limited and less invasive sampling methods are desired, liquid biopsy has gained traction among ICI-treated patients, as reported at the ESMO Immuno-Oncology Congress 2024.

One study presented as a poster focused on blood DNA methylation profiles of advanced non-small cell lung cancer (NSCLC) patients treated with ICIs using Infinium Methylation EPICv2.0 microarrays (Abstract 24P). The researchers found that the blood methylation profile remained stable between baseline and follow-up, suggesting its potential as a stable, therapy-independent biomarker.

Another study aimed to identify circulating biomarkers for patient selection and stratification in advanced NSCLC (Abstract 28P). It revealed increased somatic mutation rates and neutrophil-to-lymphocyte ratios (NLR) at disease progression in NSCLC patients treated with ICIs.

Liquid biopsy's prognostic role was also explored in other studies. One poster examined the role of circulating tumor DNA (ctDNA) in metastatic uveal melanoma, finding that ctDNA levels were predictive of progression-free and overall survival in patients receiving first or subsequent lines of therapy (Abstract 25P).

In another study, researchers sought to overcome the limitations of tissue-based combined positive scores (CPS) in predicting ICI response in recurrent and/or metastatic squamous cell carcinoma of the head and neck (Abstract 27P). Their results indicated that analyzing peripheral immune cell populations could predict PD-1 inhibitor efficacy in this patient group.

A critical aspect of liquid biopsy in immuno-oncology is its potential to address immune-related adverse events (irAEs) in ICI-treated patients. Currently, the lack of reliable predictive biomarkers for irAEs is a significant concern. A pivotal study presented at the congress suggested that changes in the balance of neutrophils and specific CD4+ T cell subpopulations were associated with irAEs (Abstract 37P). This finding marks a significant step toward identifying biomarkers that could predict irAEs, thereby reducing the need for immunosuppressive treatments that may compromise ICI efficacy.

Collectively, these findings further support the role of liquid biopsy in the administration of ICIs. However, there is a strong need for prospective clinical trials in this field.