Immune checkpoint inhibitors can cause serious immune-related adverse events
A study released in June of this year by Grover et al in the Journal of Cancer is the first to find a correlation between the use of vitamin D before the start of treatment and the decreased risk of colitis by immune checkpoint inhibitors (ICIs).
ICIs can cause serious immune-related adverse events, often impacting therapy continuity. Colitis, for example, is one of the most serious adverse reactions and its incidence is higher in those using anti-CTLA4 drugs. Depending on the degree of colitis involvement and the patient’s clinical conditions, medications such as corticosteroids, infliximab, mycophenolate or monoclonal antibodies (vedolizumab) may be indicated.
Research in mice already suggests that vitamin D can modulate the immune system and protect against inflammatory bowel diseases, such as ulcerative colitis and Crohn’s disease. The researchers in this study then performed a retrospective analysis of melanoma patients treated at the Dana-Farber Cancer Institute who received anti-PD-1, anti-CTLA-4 or combined ICIs between May 2011 and October 2017. An external confirmation was carried out from an independent cohort at Massachusetts General Hospital.
The team classified vitamin D intake into three dosage categories: no use, use ≤ 1000 IU / day and use> 1000 IU / day, based on recommended vitamin D supplementation and daily replacement guidelines. The primary endpoint was the development of ICI-related colitis, confirmed with flexible sigmoidoscopy and colon biopsy.
In total, 213 patients were included, of whom 37 developed ICI colitis (17%). Vitamin D use was recorded in 66/213 patients (31%) before starting ICI. In multivariate regression analysis, the use of vitamin D conferred significantly reduced chances 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%).
The authors concluded that patients who took vitamin D at the time of their first ICI treatment had significantly reduced chances of developing ICI colitis during their immunotherapy regimen.
These results suggest benefits of prophylactic use of vitamin D supplements to prevent ICI colitis, as previously described in inflammatory bowel disease and graft versus host disease. However, it is emphasized that this research has a retrospective design, requiring prospective trials, in order to adequately guide doctors and patients as to the indications for possible supplementation in this setting.
Grover S, Dougan M, Tyan K, Giobbie‐Hurder A, Blum SM, Ishizuka J, Qazi T, Elias R, Vora KB, Ruan AB, Martin‐Doyle W. Vitamin D intake is associated with decreased risk of immune checkpoint inhibitor‐induced colitis. Cancer. 2020 Jun 22.