Immunotherapy drugs called Immune Checkpoint Inhibitors (ICIs) work by blocking checkpoint proteins from binding with their partner proteins, preventing the “off” signal from being sent, and allowing the T cells to kill cancer cells.
However this augmented immune response can also lead to a range of systemic and organ specific immune‐related adverse effects (irAE).
ICI‐induced colitis shares similar characteristics with inflammatory bowel disease, albeit more aggressive. Several individual and environmental risk factors have been associated with the risk of IBD. High vitamin D levels are a known protective factor for both CD and UC. A range of comorbidities have also been shown to correlate with IBD, including autoimmune disease and eosinophilia. But there are comparatively few predictive markers for determining ICI‐induced colitis risk.
In the current study, published in the ACS journal Cancer, a collaborative team including researchers from Harvard Medical School and Brigham and Women's Hospital in Boston, Massachusetts, conducted a retrospective analysis of more than 200 melanoma patients to identify potential factors associated with development of ICI colitis.
They conclude that patients taking vitamin D at the time of their first ICI treatment had significantly reduced odds of developing ICI colitis over the course of their immunotherapy.
246 patients were identified from Dana-Farber Cancer Institute's melanoma bio‐specimen banking protocol and 23 patients were excluded due to lack of immune related adverse effects.
Patients received at least one course of ICI treatment (pembrolizumab, nivolumab, or/and ipilimumab) between May 2011 to October 2017.
Characteristics and concomitant medications records and pre‐treatment use of vitamin D were recorded at the time of the first ICI treatment.
Researchers noted any infections (pneumonia, bacteremia, UTI, or sepsis) within six months of initiating ICIs, as well as comorbidities including autoimmune disease, asthma, or seasonal allergies. Tumor characteristics, including prior therapy within six months of the ICIs initiation, common tumor mutations, and number of metastatic sites were also collected.
Histopathological biopsies of the colon revealed which patients developed immune‐related colitis.
External confirmation of the results was performed on an independent cohort of 169 melanoma patients treated with ICIs.
The researchers conclude that patients taking vitamin D had significantly reduced odds of developing ICI colitis over the course of their immunotherapy regimen.
The report states: "These results may suggest benefit in prophylactic use of vitamin D supplementation to prevent ICI colitis, as previously demonstrated in inflammatory bowel disease and graft‐versus‐host disease."
There are a number of limitations with retrospective studies, not least that they can only show association, not causation. The report therefore suggests prospective studies should be undertaken to decipher a causal link.
"The specific mechanism by which vitamin D may prevent immune‐related colitis should be further explored through future correlative studies, including cytokine analyses and immune profiling at baseline and at the time of colitis. 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."
Grover. S., et al
Vitamin D intake is associated with decreased risk of immune checkpoint inhibitor‐induced colitis