Vitamin D may help reduce colitis risk during immunotherapy

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Taking vitamin D supplements might reduce the risk of colitis in patients receiving immune checkpoint inhibitors to treat their cancer, found a US study.

Immune checkpoint inhibitors help the immune system recognise and combat cancer cells, and although these treatments have helped many patients and have prolonged lives, they can cause side effects such as colitis, an inflammatory reaction in the colon. “Immune checkpoint inhibitor-induced colitis can limit the use of such life-saving drugs leading to discontinuation of treatment. While it is one of the most common and severe adverse events of immunotherapy, there is a lack of understanding of the risk factors that could be modified to prevent colitis,” said Dr Osama Rahma, of the Dana-Farber Cancer Institute and Harvard Medical School, in Boston.

Rahma and his colleagues conducted a study that examined whether taking vitamin D supplements might reduce the risk of colitis in patients receiving immune checkpoint inhibitors to treat their cancer. The team chose this strategy because previous studies have found that vitamin D may affect the immune system in cases of autoimmune disorders and inflammatory bowel disease.

The study included information on 213 patients with melanoma who received immune checkpoint inhibitors between 2011 and 2017. Thirty-seven (17%) of these patients developed colitis. Sixty-six patients in the study (31%) took vitamin D supplements before starting treatment with immune checkpoint inhibitors.

Patients who took vitamin D had 65% lower odds of developing colitis, after adjustments for confounding factors. These findings were validated in another group of 169 patients, of whom 49 (29%) developed colitis. In this validation group, use of vitamin D was linked with 54% lower odds of developing colitis.

“Our findings of a link between vitamin D intake and reduced risk for colitis could potentially impact practice if validated in future prospective studies,” said Rahma.

“Vitamin D supplementation should be tested further to determine if it could be a safe, easily accessible, and cost-effective approach towards preventing immunotherapy’s gastrointestinal toxicity and extending the effectiveness of immune checkpoint inhibitor treatment in cancer patients.”

Abstract
Background: There is a lack of predictive markers informing on the risk of colitis in patients treated with immune checkpoint inhibitors (ICIs). The aim of this study was to identify potential factors associated with development of ICI colitis.
Methods: We performed a retrospective analysis of melanoma patients at Dana‐Farber Cancer Institute who received PD‐1, CTLA‐4, or combination ICIs between May 2011 to October 2017. Clinical and laboratory characteristics associated with pathologically confirmed ICI colitis were evaluated using multivariable logistic regression analyses. External confirmation was performed on an independent cohort from Massachusetts General Hospital.
Results: The discovery cohort included 213 patients of whom 37 developed ICI colitis (17%). Vitamin D use was recorded in 66/213 patients (31%) before starting ICIs. In multivariable regression analysis, vitamin D use conferred significantly reduced odds of developing ICI colitis (OR 0.35, 95% CI 0.1–0.9). These results were also demonstrated in the confirmatory cohort (OR 0.46, 95% CI 0.2–0.9) of 169 patients of whom 49 developed ICI colitis (29%). Pre‐treatment neutrophil‐to‐lymphocyte ratio (NLR) ≥5 predicted reduced odds of colitis (OR 0.34, 95% CI 0.1–0.9) only in the discovery cohort.
Conclusions: This is the first study to report that among patients treated with ICIs, vitamin D intake is associated with reduced risk for ICI colitis. This finding is consistent with prior reports of prophylactic use of vitamin D in ulcerative colitis and graft‐versus‐host‐disease. This observation should be validated prospectively in future studies.

Authors
Shilpa Grover, Michael Dougan, Kevin Tyan, Anita Giobbie‐Hurder, Steven M Blum, Jeffrey Ishizuka, Taha Qazi, Rawad Elias, Kruti B Vora, Alex B. Ruan, William Martin‐Doyle, Michael Manos, Lauren Eastman, Meredith Davis, Maria Gargano, Rizwan Haq, Elizabeth I Buchbinder, Ryan J Sullivan, Patrick A Ott, F Stephen Hodi, Osama E Rahma

 

Wiley material

 

Cancer abstract

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