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Plasma biomarker may identify response to PD-1 inhibitor Tx for melanoma

In a new study, researchers have discovered that a specific liquid biopsy biomarker could potentially be used to assess the effectiveness of melanoma treatment at an early stage.

The authors of the paper, published in Clinical Chemistry (March 2024; 70(3):516–527), say the use of this biomarker could enable a more individualized treatment for patients with melanoma.

In a press release, study author Dr. Simon Fietz notes that while PD-1 inhibitor treatment is commonly used for palliative or adjuvant therapy in patients with melanoma, it does not work for all patients.

“Some patients are resistant or develop resistance during treatment,” says Dr. Fietz, assistant physician at the Clinic for Dermatooncology & Phlebology at the Centre for Skin Diseases at the University Hospital Bonn (UKB), Germany. “In our study, we have now developed a method which we can use to find out who will respond to the treatment and when the therapy should be changed at an early stage.”

The researchers analyzed the blood of both patients with and without tumours for biomarkers and found that a certain biomarker (SHOX2 methylation of circulating cell-free DNA in blood plasma) derives directly from the tumour cells. They analyzed a total of 42 patients undergoing palliative and 55 patients undergoing adjuvant anti-PD-1 immunotherapy. Another 126 patients without cancer were used as controls.

The research group examined the SHOX2 methylation status in the blood plasma before and four weeks after the start of treatment to predict and evaluate response to therapy and survival. They found that SHOX2 methylation levels were elevated in 60% of melanoma patients, while 98% of the control group showed low levels. In addition, patients with elevated levels before treatment which decreased after four weeks responded particularly well.

“The results of our study suggest that SHOX2 methylation in the blood could be a promising predictor of response to anti-PD-1 therapy in melanoma patients. Therefore, testing for this biomarker can support individualized treatment decision-making by indicating the effectiveness of anti-PD-1 therapy at an early stage,” says Dr. Fietz. “Additionally, this biomarker test also helped us to detect metastases in patients undergoing adjuvant therapy at an early stage.”

To build on these findings, a larger follow-up study is now underway at the UKB, in which various biomarkers are being combined.

“By combining [biomarkers], we aim to achieve even greater precision and reliability in diagnostics in order to improve patient care for those affected by melanoma,” says Dr. Fietz.


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