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维生素 D 补充剂可提高接受抗 PD-1 治疗的晚期黑色素瘤患者的客观缓解率并延长无进展时间。

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

机构信息

Department of Medical and Experimental Oncology, Institute of Oncology, Poznan University of Medical Sciences, Poznań, Poland.

Department of Computer Science and Statistics, Poznan University of Medical Sciences, Poznań, Poland.

出版信息

Cancer. 2023 Jul 1;129(13):2047-2055. doi: 10.1002/cncr.34718. Epub 2023 Apr 24.

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.

摘要

背景

维生素 D3 是一种具有多种作用的前激素,包括调节免疫系统的功能,并且可能影响癌症患者接受抗 PD-1 治疗的效果。根据文献,维生素 D 影响治疗效果的潜在机制很可能与肿瘤浸润淋巴细胞的数量和活性有关。有数据表明维生素 D 对调节 CD8 淋巴细胞活性的细胞有影响。

方法

本研究共纳入 200 例晚期黑色素瘤患者。所有患者均接受抗 PD-1 免疫治疗(纳武利尤单抗或帕博利珠单抗)作为一线治疗。在治疗期间,每 12 周测量一次患者的血清维生素 D 水平。部分患者的维生素 D 水平从保存的血清中进行回顾性测量。另一部分补充组进行前瞻性检测。

结果

维生素 D 水平低且未补充的组的缓解率为 36.2%,而基线水平正常或补充后水平正常的组的缓解率为 56.0%(p=0.01)。此外,这些组的无进展生存期分别为 5.75 和 11.25 个月(p=0.03)。在总生存期方面,维生素 D 水平正常的组也有优势(分别为 27 个月和 31.5 个月;p=0.39)。

结论

在我们看来,在晚期黑色素瘤患者接受抗 PD-1 免疫治疗期间,将维生素 D 水平维持在正常范围内应该是一种标准程序,可以改善治疗效果。

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