Journal of Translational Medicine (Oct 2023)

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

  • Domenico Mallardo,
  • Rachel Woodford,
  • Alexander M. Menzies,
  • Lisa Zimmer,
  • Andrew williamson,
  • Egle Ramelyte,
  • Florentia Dimitriou,
  • Alexandre Wicky,
  • Roslyn Wallace,
  • Mario Mallardo,
  • Alessio Cortellini,
  • Alfredo Budillon,
  • Victoria Atkinson,
  • Shahneen Sandhu,
  • Michielin Olivier,
  • Reinhard Dummer,
  • Paul Lorigan,
  • Dirk Schadendorf,
  • Georgina V. Long,
  • Ester Simeone,
  • Paolo A. Ascierto

DOI
https://doi.org/10.1186/s12967-023-04607-4
Journal volume & issue
Vol. 21, no. 1
pp. 1 – 11

Abstract

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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 ( 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.

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