Elective Colectomy in a Patient with Active Ulcerative Colitis and Metastatic Melanoma Enabling Successful Treatment with Immune Checkpoint Inhibitors

Abstract

Checkpoint inhibitor immunotherapy has significantly advanced treatment of a growing number of advanced malignancies. A consequences of immune system activation that leads to tumor cell destruction by checkpoint inhibitor therapy is the development of immune-related adverse events, some of which can be life threatening. There are limited data on the use of checkpoint inhibitor therapy in patients with preexisting autoimmunity owing to concerns that underlying autoimmune disease may be exacerbated by checkpoint inhibitor treatment. Decisions to treat these patients are made after careful consideration of the risks and benefits of treatment. We describe a patient with active and severe ulcerative colitis with metastatic melanoma who underwent elective colectomy prior to initiation of anti-PD-1 and anti-CTLA-4. The patient had excellent tumor response without flare of his ulcerative colitis suggesting that in select patients with high-risk inflammatory bowel disease, elective colectomy may be an effective treatment option.

Keywords: Checkpoint; Colitis; Complications; Immunotherapy; Inflammatory bowel disease.

Figure 1:

CT and MRI scans pre-and post-checkpoint inhibitor therapy; (A) Pretreatment CT chest scan showing a 7.2 cm right axillary metastasis. Decrease in the size of metastases and ongoing response was observed at 1 year (following 12 cycles of therapy) with imaging showing a stable node measuring 3.5 cm (white arrows); (B) Post-SRS and pre-CPI brain MRI scan demonstrating right and left sided supratentorial metastatic lesions on contrast-enhanced MPRAGE imaging and corresponding edema on FLAIR. Post-CPI treatment scan shows no evidence of residual metastasis at 1 year. Arrow head shows resolution of the largest lesion on the left.

Figure 2:

Pathology of colectomy specimen; (A) Gross appearance of sessile carpet-like polypoid lesion in the ascending colon (arrow) from the colectomy specimen. The adjacent mucosa is irregular and erythematous with loss of normal mucosal folds (asterisk); (B) On microscopy, the colonic mucosa was diffusely involved by chronic colitis, characterized by crypt distortion, basal plasmacytosis, and regenerative changes. The inflammation is limited to the mucosa (H and E, 4x); (C) Low power view of the ascending colon sessile lesion reveals proliferative mucosa forming polypoid structures (H and E, 4x); (D) On higher magnification, multiple areas of low-grade dysplasia (arrow) are seen. Compared to adjacent reactive epithelium (arrowhead) dysplastic foci show increased nuclear size, hyperchromasia, stratification and mucodepletion (H and E, 20X).

Figure 3:

Cytokine levels pre- and post-CPI therapy for case patient with ulcerative colitis (UC hx) and two control (CTRL) patients without underlying colitis or other autoimmune diseases. CTRL 1 is a 39-year-old male with metastatic melanoma to the parotid gland and lymph nodes on nivolumab (pre-and post-treatment samples are 4 weeks apart, 1 cycle of nivolumab) and CTRL 2 is a 36-year-old male with metastatic melanoma to lymph nodes on nivolumab (pre-and post-treatment samples are 4 weeks apart, 1 cycle of nivolumab). The pre-treatment sample for the UC case was 25 days after colectomy. Pre-and post-treatment samples for the UC case patient are 4 weeks apart (2 cycles of nivolumab). None had significant complications at the time of the post-treatment collection. Data represent average of replicate analytes.