Abstract
BackgroundImmune checkpoint inhibitors (ICIs) have been used to treat many cancers, but ICIs are rarely administered for malignant tumours coexisting with inflammatory bowel disease.Methods and resultsWe report a 77-year-old man experiencing an ulcerative colitis (UC) flare-up after receiving nivolumab as third-line therapy for multiple metastases of renal cell carcinoma. Mild UC (proctitis form) had been diagnosed at age 59 years and remission was maintained for 17 years with only a low dose of 5-ASA. After nivolumab treatment, the patient developed diarrhoea, bloody stools and was hospitalised. Computed tomography revealed inflammation involving the entire colon and endoscopy revealed severe UC exacerbation. Histological analysis showed UC findings and also increased crypt apoptosis which is unusual for inflammatory bowel diseases, while being typical of ICI-induced colitis. As with ICI-induced colitis, this exacerbation was strongly suggested to have been caused by nivolumab, although remission was achieved by increasing the 5-ASA dose to 4000 mg without prednisolone.ConclusionThe administration of ICI for UC is not as yet sufficiently safe and further research is required.
Highlights
Nivolumab and other immune checkpoint inhibitors (ICIs), which have shown high efficacy against a variety of cancers in recent years, promise long-term survival and even recovery
Patients with autoimmune diseases such as inflammatory bowel disease (IBD) have historically been excluded from clinical trials of Immune checkpoint inhibitors (ICIs), and there are few reports of programmed cell death protein-1 (PD-1) inhibitors administered to patients with a pre-existing form of IBD [13, 14]
Histological analysis revealed erosion, reduced goblet cells, irregular duct layout, cryptitis, crypt abscesses and chronic inflammatory cell infiltrate in the stroma. These findings were consistent with ulcerative colitis (UC) flare-up, but after recognising increasing apoptosis, we considered the possibility of PD-1 inhibitor-induced enterocolitis to be high (Fig. 2a, b)
Summary
We report a 77-year-old man experiencing an ulcerative colitis (UC) flare-up after receiving nivolumab as third-line therapy for multiple metastases of renal cell carcinoma. Mild UC (proctitis form) had been diagnosed at age 59 years and remission was maintained for 17 years with only a low dose of 5-ASA. The patient developed diarrhoea, bloody stools and was hospitalised. Computed tomography revealed inflammation involving the entire colon and endoscopy revealed severe UC exacerbation. Histological analysis showed UC findings and increased crypt apoptosis which is unusual for inflammatory bowel diseases, while being typical of ICI-induced colitis. As with ICI-induced colitis, this exacerbation was strongly suggested to have been caused by nivolumab, remission was achieved by increasing the 5-ASA dose to 4000 mg without prednisolone
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