Metastatic melanoma remains a deadly disease. However, novel immunotherapies such as immune checkpoint inhibitors (ICI), significantly improved 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 treatment termination. Therefore to increase the success of these immunotherapies in metastatic melanoma, novel treatment markers that can predict the patients treatment success or toxicity are urgently needed. Availability of such markers will substantially improve treatment success, further reducing mortality of metastatic melanoma.
Inherited (germline) genetics may play an important role in shaping individual’s immune system. We are investigating which inherited genetic factors determine how patients’ host immunity responds to these therapies or confer sensitivity to treatment toxicity. This knowledge contributes to better prediction of treatment success or risk of toxicity for each treated patient.
This research requires a large number of patients, which has prevented success of such efforts in the past. Therefore, we have created a large international consortium with >45 prominent cancer centers in the world pooling >9,800 metastatic melanoma patients treated with ICI immunotherapy. This allows large novel genetic analysis testing of each individual genome for the identification of inherited markers that predict immunotherapy success and toxicity. Once identified, we will also test these clinically relevant markers in biological experiments for the potential to serve as novel targets of improved immunotherapy in metastatic melanoma.
John Haanen (AVL-NKI), Remco van Doorn, (LUMC), Tomas Kirchhoff, Jeffrey Weber, Yongzhao Shao, Jun Wang and Robert Ferguson (New York University)