Vitamin D may reduce risk for immune checkpoint inhibitor-induced colitis
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Use of vitamin D supplements appeared to reduce risk for colitis among patients with cancer treated with immune checkpoint inhibitors, according to results of a retrospective study published in Cancer.
“Immune checkpoint inhibitor-induced colitis can limit the use of such life-saving drugs, leading to discontinuation of treatment,” Osama E. Rahma, MD, medical oncologist at Dana-Farber Cancer Institute, said in a press release. “[Although] 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.”
Previous studies have shown that prophylactic vitamin D may reduce risks for ulcerative colitis and graft-versus-host disease. However, few predictive markers exist to identify the risk for colitis among patients treated with immune checkpoint inhibitors.
Rahma and colleagues retrospectively analyzed 213 patients with melanoma who received PD-1, CTLA-4 or combination immune checkpoint inhibitors between May 2011 and October 2017 to determine the characteristics associated with pathologically confirmed immune checkpoint inhibitor-induced colitis.
Forty-nine patients received more than one checkpoint inhibitor regimen during the course of treatment, resulting in 267 individual regimens. These included ipilimumab (Yervoy, Bristol-Myers Squibb; n = 66), nivolumab (Opdivo, Bristol-Myers Squibb; n = 17), pembrolizumab (Keytruda, Merck; n = 91) and a combination of ipilimumab and nivolumab (n = 93).
Among all patients, 66 began taking vitamin D supplements before starting checkpoint inhibitor therapy and 37 developed checkpoint inhibitor-induced colitis.
A multivariable regression analysis showed vitamin D use significantly reduced the risk for developing checkpoint inhibitor-induced colitis (OR = 0.35; 95% CI, 0.1-0.9). Researchers validated the findings in a confirmatory cohort of 169 patients, of whom 49 (29%) developed colitis (OR = 0.46; 95% CI, 0.2-0.9).
Compared with pembrolizumab monotherapy, risk for checkpoint inhibitor-induced colitis appeared significantly higher among those treated with the combination of ipilimumab and nivolumab (OR = 3.34; 95% CI, 1.1-9.8) and ipilimumab alone (OR = 7.48; 95% CI, 2.6-21.8). Those treated with ipilimumab monotherapy also demonstrated increased risk for colitis compared with a pooled PD-1 monotherapy group of pembrolizumab or nivolumab (OR = 7.14; 95% CI, 2.2-25).
Pretreatment neutrophil-to-lymphocyte ratio of 5 or greater predicted reduced odds of colitis in the discovery cohort only (OR = 0.34; 95% CI, 0.1-0.9).
“Our findings of a link between vitamin D intake and reduced risk for colitis could potentially impact practice if validated in future prospective studies,” Rahma said in the press release. “Vitamin D supplementation should be tested further to determine if it could be a safe, easily accessible and cost-effective approach toward preventing immunotherapy’s gastrointestinal toxicity and extending the effectiveness of immune checkpoint inhibitor treatment [for patients with cancer].”
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