The role of diabetes in metastatic melanoma patients treated with nivolumab plus relatlimab

• Published in: Journal of translational medicine Vol. 21; no. 1; pp. 1 - 11
• Main Authors: Mallardo, Domenico, Woodford, Rachel, Menzies, Alexander M., Zimmer, Lisa, williamson, Andrew, Ramelyte, Egle, Dimitriou, Florentia, Wicky, Alexandre, Wallace, Roslyn, Mallardo, Mario, Cortellini, Alessio, Budillon, Alfredo, Atkinson, Victoria, Sandhu, Shahneen, Olivier, Michielin, Dummer, Reinhard, Lorigan, Paul, Schadendorf, Dirk, Long, Georgina V., Simeone, Ester, Ascierto, Paolo A.
• Format: Journal Article
• Language: English
• Published: London BioMed Central Ltd 25.10.2023; BioMed Central; BMC
• Subjects: Analysis; Blood levels; Cancer; Care and treatment; Development and progression; Dextrose; Diabetes; Diabetes mellitus (non-insulin dependent); Diabetes therapy; Diagnosis; Drug therapy; Glucose; Health aspects; Immune checkpoint inhibitors; Immunotherapy; Ipilimumab; LDH; Medical prognosis; Melanoma; Metastases; Metastasis; Monoclonal antibodies; Multivariate analysis; Nivolumab + relatlimab; PD-1 protein; Prevention; Response rates; Risk factors; Targeted cancer therapy; Type 2 diabetes; White people; Italy
• ISSN: 1479-5876; 1479-5876
• DOI: 10.1186/s12967-023-04607-4

Background The combination of nivolumab + relatlimab is superior to nivolumab alone in the treatment of naive patients and has activity in PD-1 refractory melanoma. We had previously observed a reduced expression of LAG3 in melanoma tissue from patients with type 2 diabetes. Method To evaluate the impact of diabetes on oncological outcomes of patients with advanced melanoma treated with nivolumab plus the LAG3 inhibitor relatlimab we performed a retrospective multicenter study. Results Overall, 129 patients were included: 88 without diabetes before the treatment, 37 who were diagnosed with type 2 diabetes before the start of treatment, and 4 without diabetes before treatment who developed immune checkpoint inhibitor-induced diabetes (ICI-DM). PFS was 21.71 months (95% CI: 15.61-27.81) in patients without diabetes, 10.23 months (95% CI: 5.81-14.66) in patients with type 2 diabetes, and 50.85 months (95% CI: 23.04-78.65) in patients who developed ICI-DM. OS was 37.94 months (95% CI: 31.02-44.85) in patients without diabetes, 22.12 months (95% CI: 14.41-29.85) in those with type 2 diabetes and 57.64 months (95% CI: 42.29-72.99) in those who developed ICI-DM. Multivariate analysis showed that the presence of diabetes and LDH was correlated with OS and PFS. The mean OS was 64.63 months in subjects with low levels of glucose (< 137 mg/dl) and 36.27 months in those with high levels (hazard ratio 0.16, 95% CI: 0.04-0.58; p = 0.005). The patients whose glucose blood level increased after 3 months of treatment with nivolumab + relatinib compared to baseline (ratio of blood level at baseline/after 3 months > 1.5) had a worse prognosis than those whose glucose level had not increased. This result was observed also in subgroups treated either in first line or further lines. Patients who developed ICI-DM during the study period had better outcomes than the overall population and patients without diabetes. Conclusions LAG3 inhibition for treating metastatic or unresectable melanoma has a reduced efficacy in patients with type 2 diabetes, possibly due to a low expression of LAG3 in tumor tissue. Higher level evidence should be obtained. Keywords: Diabetes, Nivolumab + relatlimab, Melanoma, LDH