The role of diabetes in metastatic melanoma patients treated with nivolumab plus relatlimab
- Author(s)
- Mallardo, D; Woodford, R; Menzies, AM; Zimmer, L; Williamson, A; Ramelyte, E; Dimitriou, F; Wicky, A; Wallace, R; Mallardo, M; Cortellini, A; Budillon, A; Atkinson, V; Sandhu, S; Olivier, M; Dummer, R; Lorigan, P; Schadendorf, D; Long, GV; Simeone, E; Ascierto, PA;
- Journal Title
- Journal of Translational Medicine
- Publication Type
- Research article
- Abstract
- 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.
- Publisher
- BioMed Central
- Keywords
- Humans; Nivolumab/therapeutic use; *Diabetes Mellitus, Type 2/complications/drug therapy; *Melanoma/complications/drug therapy/pathology; Glucose; Ipilimumab/therapeutic use; Antineoplastic Combined Chemotherapy Protocols/adverse effects
- Department(s)
- Medical Oncology
- PubMed ID
- 37880788
- Publisher's Version
- https://doi.org/10.1186/s12967-023-04607-4
- Open Access at Publisher's Site
https://doi.org/10.1186/s12967-023-04607-4- Terms of Use/Rights Notice
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Creation Date: 2023-12-05 12:35:31
Last Modified: 2023-12-05 12:50:03