Background: Magnesium deficiency influences the activation and cytotoxicity of immune cells. Nevertheless, whether serum magnesium levels influence the clinical outcomes of immune checkpoint blockers (ICBs) treatment still remains ambiguous. There is an urgent need for clinical research to elucidate the relationship between serum magnesium levels and the outcomes of ICB therapy. Such insights could offer new perspectives on immunotherapy for cancer.
Methods: A multi-center retrospective study involving in pan-cancer patients treated with ICBs at three large cancer centers from August 2012 to May 2023 was conducted. The primary objective was to assess the correlation between serum magnesium levels and therapeutic response in patients receiving ICBs, and further evaluate the associations between serum magnesium levels and progression-free survival (PFS) and overall survival (OS).
Results: A total of 1441 patients treated with ICBs, including 1042 with lung cancer, 270 with esophageal cancer, and 129 with Hodgkin lymphoma, were enrolled in this study. We found that patients with elevated serum magnesium levels exhibited a favourable response to ICBs treatment. The optimal cut-off point for serum magnesium level (0.79 mmol/L) was applied for stratifying patients into distinct groups. In the three tumor cohorts, patients in high magnesium level group (Mg2+ ≥ 0.79 mmol/L) had longer PFS and OS than those in low magnesium level group (Mg2+ < 0.79 mmol/L). Univariate and multivariate analyses confirmed that the serum Mg2+ level serves as an independent prognostic factor for cancer patients receiving ICBs therapy.
Conclusion: Our multi-center study demonstrated that among patients receiving ICBs therapy, those with elevated serum magnesium levels exhibit significantly better clinical outcomes than those with low serum magnesium levels. Further prospective validation studies are needed to confirm these findings.
Keywords: Esophageal cancer; Immune checkpoint blockers; Lung cancer; Lymphoma.
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