Ongoing
Biomarkers that predict immunotherapy treatment success or risk of toxicity are urgently needed to increase clinical benefits for metastatic melanoma patients. Amsterdam UMC, the Netherlands Cancer Institute and New York University have jointly created an international consortium to study inherited (germline) genetics as biomarkers for melanoma patients.

Metastatic melanoma remains a deadly disease. However, novel immunotherapies such as immune checkpoint inhibitors (ICI) significantly improve the survival of melanoma patients. Nevertheless, only about 50% of metastatic melanoma patients benefit from these therapies and >90% of treated patients show toxicities that often require termination of treatment. Therefore, to increase the success of these immunotherapies in metastatic melanoma, novel markers that can predict treatment outcome are urgently needed.

Inherited (germline) genetics may play an important role in shaping an individual’s immune system. We are investigating which inherited genetic factors influence how the patients’ immune system responds to immunotherapies. This knowledge will contribute to better predictions of treatment success or risk of toxicity for each treated patient. This kind of research requires a large number of patients, which has prevented the success of such efforts in the past.

Therefore, we have created a large international consortium with over 45 prominent cancer centers in the world, pooling more than 9,800 metastatic melanoma patients treated with ICI immunotherapy. Genetic analysis of each individual genome will provide a robust dataset for the identification of inherited markers that predict immunotherapy success and toxicity. Once identified, we will test these clinically relevant markers in biological experiments for their potential to serve as novel drug targets to improve immunotherapy in metastatic melanoma.

Researchers involved

John Haanen (AVL-NKI), Remco van Doorn, (LUMC), Tomas Kirchhoff, Jeffrey Weber, Yongzhao Shao, Jun Wang and Robert Ferguson (New York University)