Vitamin D supplementation increases objective response rate and prolongs progression‐free time in patients with advanced melanoma undergoing anti–PD‐1 therapy

Abstract

Background Vitamin D3 is a prohormone with pleiotropic effects, including modulating the functions of the immune system and may affect the effectiveness of anti–PD‐1 treatment in patients with cancer. According to the literature, the potential mechanism of vitamin D's influence on the effectiveness of therapy is most likely related to the amount and activity of tumor‐infiltrating lymphocytes. There are data showing the effect of vitamin D on cells regulating the activity of CD8 lymphocytes. Methods A total of 200 patients with advanced melanoma were included in the study. All patients received anti–PD‐1 immunotherapy (nivolumab or pembrolizumab) as first‐line treatment. Serum vitamin D levels were measured in patients both before and every 12 weeks during treatment. Part of the group had vitamin D measured retrospectively from the preserved serum. The other part of the supplementation group was tested prospectively. Results The response rate in the group with low vitamin D levels and not supplemented was 36.2%, whereas in the group with normal baseline levels or a normal level obtained with supplementation was 56.0% (p = .01). Moreover, progression‐free survival in these groups was 5.75 and 11.25 months, respectively (p = .03). In terms of overall survival, there was also a difference in favor of the group with normal vitamin D levels (27 vs. 31.5 months, respectively; p = .39). Conclusions In our opinion, maintaining the vitamin D level within the normal range during anti‐PD‐1 immunotherapy in advanced melanoma patients should be a standard procedure allowing the improvement of treatment outcomes.

Vitamin D regulates microbiome-dependent cancer immunity

“…Similarly, VDR expression in melanoma correlates with immune score and increased patient survival, possibly because VDR signals help counteract immunosuppressive Wnt signaling ( 69 ). Notably, a recent study has reported that greater VitD levels at baseline or after dietary correction correlate with higher responsiveness to immune checkpoint blockade therapy in a cohort of advanced melanoma patients ( 70 ). Thus, in humans, as in mice, VitD activity appears to potentiate immune responses to cancer.…”

Dietary factors and their influence on immunotherapy strategies in oncology: a comprehensive review

“…Vitamin D, further, upregulates MAP kinases, inhibits the NF-kB signaling pathway, regulates cytokine levels, and modulates the interaction between tumor cells and immune cells. It also plays a role in regulating the prostaglandin pathway [ 109 , 110 ].…”

“…However, it is also important to maintain a stable vitamin D level within the normal level during anti-PD-1 immunotherapy, which improves patients’ prognosis [ 110 ].…”

Vitamin and Mineral Supplementation, Weight Gain, and Poor Appetite in Patients With Cancer: Many Questions and Fewer Answers

“…Although this study did not report on whether these micronutrient deficiencies were remedied, such supplementation should perhaps be considered in the face of such deficiencies. As another example, Galus et al 14 studied 200 patients with melanoma, all of whom were receiving anti–programmed death-L1 therapy. Serum vitamin D levels were assessed.…”