Identifying Enhanced Response to Immunotherapy in Melanoma
Data presented at this year’s Society for Immunotherapy of Cancer annual meeting analyzes different biomarkers to help identify which melanoma patients will respond better to immunotherapy treatment. Two comprehensive biomarker studies, performed at Moffitt Cancer Center in collaboration with ECOG-ACRIN Cancer Research Group and other national cancer centers and led by Dr. Ahmad Tarhini, investigated if patient gender plays a role in response to immunotherapy in melanoma. Separately, a second study investigated a group of melanoma patients who presented with advanced metastatic melanoma without a known history of a primary melanoma on the skin.
In the first study, researchers found female melanoma patients had better outcomes overall, responded better to immunotherapy and had better survival rates than male patients.
Dr. Ahmad Tarhini, Senior Member and Director of Cutaneous Clinical and Translational Research
“We have known that female sex hormones have been implicated in melanoma development and response to systematic therapy and that was the trigger for us to conduct this in-depth analysis, focusing on patients treated with modern immune checkpoint inhibitors,” said Tarhini, a medical oncologist, scientist and senior member and director of Cutaneous Clinical and Translational Research at Moffitt. “We found evidence of immune related pathways and genes related to immune cell infiltration and activation that were significantly enriched in the tumors of females compared to males. Interestingly, in testing blood-based biomarkers, we also found evidence of more enhanced immune activation in females compared to males.”
While female patients responded better, male patients also responded well to immunotherapy. Besides gender, there are also other tumor-related, patient-related and environmental factors — such as diet and exercise — that can affect a patient’s treatment response.
In the second study, researchers compared advanced melanoma patients with known primary tumor origin with those with unknown primary tumor origin. About 13% of the study participants were diagnosed with advanced metastatic melanoma with an unknown origin, and results showed they responded better to immunotherapy and had a better prognosis overall.
“We believe that unknown primary melanoma tumors initially present in areas of the body that were previously recognized by the immune system. While this can lead to elimination of the primary tumor by the immune system, some tumor cells may escape and take refuge in other parts the body until they eventually evolve and develop immune resistance. This allows them to progress,” said Tarhini. “We identified pathways and genes related to autoimmunity, inflammation, immune cell infiltration and immune activation that were significantly enriched in the unknown primary tumors compared to known primaries supporting our hypothesis.”
Because the immune system may have already been stimulated to fight the cancer, it may be even further enhanced by immunotherapy, giving those patients better overall survival. The data is good news for these patients, who often are diagnosed at later stages and are uncomfortable with the fact that doctors cannot pinpoint where their cancer began.
Tarhini says because of this data, the melanoma field should start thinking about patients with melanoma of unknown origin as its own distinct prognostic group, as well as rethink how these patients’ disease is staged and how they are stratified in clinical trials.
“We are at a time where we have access to advanced technologies that allow us to interrogate individual genes and biomarkers to better understand the tumor biology and patient immunology in our efforts to advance precision medicine tailored ultimately towards the individual patient,” said Tarhini.
