Vitamin D supplementation may improve immunotherapy response in advanced melanoma
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Key takeaways:
- Patients with melanoma who had normal vitamin D levels at baseline or with supplementation had a higher response rate to immunotherapy.
- Vitamin D supplementation could be considered for these patients.
Maintenance of normal vitamin D levels during anti-PD-1 immunotherapy should be standard procedure for patients with advanced melanoma to allow for better treatment outcomes, according to a report in Cancer.
Data showed a higher objective response rate and significantly longer median PFS after anti-PD-1 therapy among patients with normal vitamin D levels compared with patients who had low levels and no supplementation.
“I have been working on the topic of the importance of proper vitamin D levels during melanoma immunotherapy for over 4 years,” Łukasz Galus, MD, of the department of medical and experimental oncology at Poznan University of Medical Sciences in Poland, told Healio. “After receiving the results, I was excited and happy. I hope that further research and confirmation of the results will lead to the widespread recommendation of vitamin D supplementation during melanoma immunotherapy and, thus, help to cure a greater percentage of patients.”
Background and methodology
Approximately one in three people in the United States has vitamin D deficiency, with prevalence rising to 90% in some populations around the world, such as northern Europe, Middle Eastern regions and parts of Asia.
Calcitriol, the hormonally active form of vitamin D, acts as a transcription factor for many genes, and cholecalciferol (vitamin D3) may affect anti-PD-1 treatment in patients with cancer, according to study background.
Galus and colleagues investigated the effectiveness of anti-PD-1 therapy in relation to serum vitamin D levels among 200 patients with locally advanced, inoperable or metastatic melanoma.
Patients received either nivolumab (Opdivo, Bristol Myers Squibb) or pembrolizumab (Keytruda, Merck) as first-line treatment for locally advanced, inoperable or metastatic melanoma.
Researchers measured serum vitamin D levels measured before and every 12 weeks during treatment. They separated patients into subgroups, one of which included those who had vitamin D levels within normal limits at baseline or because of supplementation, and another that included patients with reduced baseline levels and no supplementation or those who did not have normal levels despite supplementation.
Results
Patients with normal baseline vitamin D levels or normal levels obtained through supplementation had an objective response rate of 56% compared with 36.2% among those with low vitamin D levels and no supplementation (P = .01). Patients with normal vitamin D levels at baseline or through supplementation also had significantly longer median PFS (11.25 months vs. 5.75 months; P = .03).
Researchers reported a difference in median OS favoring the group with normal vitamin D levels (31.5 months vs. 27 months) but this did not achieve statistical significance.
Next steps
“Immunotherapy is currently experiencing a real renaissance in oncologic treatment. It has contributed to a significant improvement in the treatment results of many advanced cancers, and in the case of melanoma it is responsible for a real revolution,” Galus told Healio. “Confirmation of our results, and possible additional studies showing that immunotherapy could be improved by such a simple method as correcting vitamin D deficiency, would be of great importance in common clinical practice and would help an additional percentage of patients.”
For more information:
Łukasz Galus, MD, can be reached at lukasz_galus@wp.pl.
Perspective
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James Isaacs, MD
Immune therapy has dramatically improved outcomes in metastatic melanoma.Underlying health status and the function of the immune system at baseline likely play a large role in the ability of patients to respond to treatment.
A growing area of research focuses on how diet or other interventions that affect nutritional status may enhance the benefit of therapy.
The study by Galus and colleagues adds important insights by evaluating patients with advanced melanoma to determine how vitamin D status affects anti-PD-1 treatment outcome.
These findings are intriguing, as they support a hypothesis that vitamin D supplementation may augment the immune system and allow for higher treatment efficacy. Vitamin D supplementation is a very feasible intervention with minimal toxicity, and it already is recommended for several additional health benefits, notably bone health.
However, as an observational study, the association of treatment outcome with vitamin D can only be concluded as correlative. Normal vitamin D is associated with treatment response but may not be the factor directly improving treatment response. Study investigators should be commended for performing a multivariate analysis, which does control for several confounding factors, including stage, lactate dehydrogenase levels and ECOG performance status.
Emerging evidence suggests that dietary interventions can improve outcomes with immune therapy for melanoma. This study adds to the literature suggesting that patients with normal vitamin D respond better to immune therapy.
Whether normal vitamin D levels reflect a superior underlying nutritional/health status that allows for strong immune response or the vitamin D itself is improving the immune response will need to be elucidated through further interventional studies. It remains critical to emphasize the importance of a healthy, well-balanced diet and other lifestyle interventions for patients undergoing treatment for melanoma.
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