Normal Vitamin D Level May Up Anti-PD-1 Response in Melanoma

Maintaining normal vitamin D levels may improve the efficacy of immunotherapy in patients with advanced melanoma, a new study suggests.

The finding comes from a study of 200 patients with melanoma who received first-line immunotherapy with the anti-programmed death-1 (anti-PD-1) inhibitors pembrolizumab (Keytruda) or nivolumab (Opdivo).

The response to treatment was significantly better in patients who had normal baseline vitamin D levels or normal vitamin D levels achieved through supplementation (>30 ng/dL), when compared with those who had low baseline vitamin D levels (≤30 ng/dL)  and no supplementation (56% vs. 36.2%; P = .0111)).

Median progression-free survival was also significantly longer in the group with normal vitamin D levels (11.2 vs 5.8 months), and overall survival favored the group with normal vitamin D levels (27 vs 31.5 months), the authors noted.

The findings were published online April 24 in the journal Cancer.

The study was conducted by Łukasz Galus, MD, of Poznan University of Medical Sciences, Poznan, Poland, and colleagues.

Study participants were patients with locally advanced, inoperable, or metastatic melanoma. Serum vitamin D levels were tested before therapy and every 12 weeks during therapy, and patients were followed for 12 months.

All patients who started treatment before July 2018 were receiving vitamin D supplementation and had their serum tested retrospectively using preserved samples, and those enrolled as of July 2018 had serum tested prospectively, the investigators said.

As to why normal vitamin D levels may boost response to immunotherapy, the authors speculate that tumor-infiltrating lymphocytes may be involved.

Existing data showing the effect of vitamin D on cells that regulate the activity of CD8 lymphocytes suggest a potential mechanism for the influence of vitamin D on immunotherapy, they noted.

“Of course, vitamin D is not itself an anti-cancer drug, but its normal serum level is needed for the proper functioning of the immune system, including the response that anti-cancer drugs like immune checkpoint inhibitors affect,” Galus said in a press statement. “In our opinion, after appropriately randomized confirmation of our results, the assessment of vitamin D levels and its supplementation could be considered in the management of melanoma.”

Galus reported receiving remuneration from BMS, Roche, MSD, Novartis, and Pierre Fabre.

Cancer. Published online April 24, 2023. Full text

Sharon Worcester, MA, is an award-winning medical journalist based in Birmingham, Alabama, writing for Medscape, MDedge and other affiliate sites. She currently covers oncology, but she has also written on a variety of other medical specialties and healthcare topics. She can be reached at  [email protected]  or on Twitter:  @SW_MedReporter

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