Vitamin D may reduce the risk of immune checkpoint inhibitor (ICI)-related colitis, according to research published in Cancer.

ICIs, including those targeting cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) and the programmed cell death-1 (PD-1)/PD-ligant 1, have improved survival outcomes in a number of cancer settings; however, immune-related adverse events (irAEs) are common with these therapies. Immune-related colitis is often the most severe of these events.

As immune-related colitis shares some phenotypic traits with Crohn disease and ulcerative colitis, researchers have previously investigated, and established, that several environmental factors, including vitamin D deficiency, are common to all forms of colitis. For this retrospective cohort study, Shilpa Grover, MD, MPH, of Harvard Medical School, and associates evaluated which individual and environmental characteristics predict immune-related colitis among patients treated with ICIs at Massachusetts General Hospital.

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Of 246 patients with melanoma who received CTLA-4, PD-1, or a combination of ICIs between 2011 and 2017, 213 were included in the discovery cohort, with an overall 267 individual ICI treatment regimens evaluated; 164 patients were treated with a single regimen, 44 patients were treated with 2 regimens, and 5 patients had 3 regimens, including 2 PD-1 ihibitors and 1 CTLA-4 inhibitor. Additionally, the investigators included external confirmation of results with an independent confirmatory cohort of 169 patients.

In the discovery group, there were 38 cases of immune-related colitis, 15 of which (39.5%) were treated with combination ipilumumab and nivolumab, 17 (44.7%) were treated with ipilimumab alone, 1 (2.6%) was treated with nivolumab alone, and 5 (13.2%) were treated with pembrolizumab.

While vitamin D use was noted in only 31% (66) of patients prior to ICI initiation, a regression analysis suggested that the supplement reduced ICI-related colitis risk (odds ratio [OR], 0.35; P =.01). Using the confirmatory cohort, the researchers confirmed these findings in a validation cohort of 49 patients with ICI-related colitis (OR, 0.46; P =.03).

Multi-variate analysis indicated that checkpoint inhibitor class, baseline neutrophil-to-lymphocyte ratio (NLR) ≥5, and vitamin D use were 3 predictors of immune-related colitis. Pretreatment NLR ≥5 predicted a reduced odds of colitis (OR, 0.34); however, NLR ≥5 was not linked to a decreased risk for ICI colitis among members of the confirmatory cohort (OR, 0.61; P =.38).

“The results from this retrospective study should be validated prospectively in larger cohorts, which may lead to a better understanding of factors that drive and prevent the development of immune checkpoint inhibitor-induced colitis,” the authors concluded.


Grover S, Dougan M, Tyan K, et al. Vitamin D intake is associated with decreased risk of immune checkpoint inhibitor‐induced colitis [published online June 22, 2020]. Cancer. doi: 10.1002/cncr.32966