Melanoma, high blood sugar halves survival of patients without diabetes

Blood glucose levels may predict the prognosis of patients with metastatic melanoma undergoing immunotherapy. In fact, if blood glucose is high, even in the absence of diabetes, the prognosis is worse and survival from the disease is halved. A study conducted by Paolo Ascierto, president of the Melanoma Foundation and director of the Melanoma Oncology, Oncologic Immunotherapy and Innovative Therapies Unit at the Pascale Institute in Naples , shed light on this association and was presented at the annual meeting of the American Society of Clinical Oncology (ASCO), currently underway in Chicago. “With the discovery of the role of blood glucose in patients with melanoma, we may have identified a new potential prognostic marker that would allow us to improve patients’ response to treatments,” comments Ascierto.

The study involved 1,079 non-diabetic patients with metastatic melanoma treated with immune checkpoint inhibitors, immunotherapy treatments that aim to remove the “brakes” that prevent the immune system from recognizing and attacking the tumor. The researchers measured blood glucose levels at three distinct times in the two weeks before the start of immunotherapy treatment, identifying a threshold value of 93.33 mg/dL.

The results showed that patients with low blood sugar had nearly double the median overall survival compared to patients with high blood sugar (27.7 months vs. 14.5 months). For progression-free survival, patients with low blood sugar had approximately 72% longer median progression-free time compared to those with high blood sugar (7.4 months vs. 4.3 months).

“The analysis of biomarkers revealed a positive association between glycemia and high levels of Interleukin-6 (IL-6), a well-known biomarker of inflammation,” explains Domenico Mallardo, Researcher at IRCCS Istituto Nazionale Tumori Fondazione G Pascale . “Furthermore, the analysis of 95 RNA samples showed an association between glycemia and genes related to inflammatory activity and cell cycle regulation.”

The implications of this study are significant and could impact the clinical management of non-diabetic patients with metastatic melanoma treated with immunotherapy . “In addition to the prognostic value, the discovery of the role of glycemia allows us to identify non-diabetic patients at greater risk of a less favorable response to immunotherapy and a more rapid progression of the disease,” Ascierto emphasizes. “Although the study did not investigate the possible effects of interventions on glycemia, the strong association between high glycemia and inflammation suggests that glycemia modulation could represent a strategy to improve the efficacy of immunotherapy. We hypothesize, in fact, that patients could benefit from lifestyle changes and dietary interventions aimed at lowering glycemia when it is above the threshold of 93.33 mg/dL.”

The development of new pharmacological approaches is not excluded either. “The association between glycemia and genes related to inflammation and cell cycle regulation provides valuable insights to better understand the molecular mechanisms through which glycemia influences the response to immunotherapy and tumor progression,” concludes Ascierto. “This could lead to the development of new therapeutic targets and targeted therapies. However, further studies are needed to confirm these results and to evaluate the efficacy of any interventions aimed at modulating glycemia in this context. If confirmed, our results could lead to the introduction of the evaluation of basal glycemia as a parameter to be considered in risk stratification and therapeutic planning for patients with metastatic melanoma treated with immunotherapy.”