Oncology and palliative care for MRCPI Part 2

A 59-year-old man receiving pembrolizumab for metastatic melanoma presents with 8 watery stools a day and abdominal cramps, three weeks after his second cycle. Stool cultures and C. difficile testing are negative. Flexible sigmoidoscopy shows diffuse colitis. What is the most appropriate treatment?

1. Continue pembrolizumab and treat symptomatically with loperamide Wrong and dangerous. Antimotility treatment alone risks progression to perforation, and continuing the drug perpetuates the injury.
2. Withhold the immunotherapy and start high-dose corticosteroids correct Correct. This is immune checkpoint inhibitor colitis, a common and potentially fatal immune-related adverse event. Treatment is to hold the drug and give high-dose corticosteroids, escalating to infliximab or vedolizumab if there is no response within a few days.
3. Elective colectomy Wrong except as a last resort for perforation or refractory disease not responding to escalating immunosuppression.
4. Switch to a different checkpoint inhibitor Wrong. The toxicity is class-related, and switching within the class risks recurrence without treating the current episode.
5. Empirical antibiotics for infective colitis Wrong. Infection has been excluded, and antibiotics delay the treatment that works.

The point: Immune-related adverse events can hit any organ: colitis, hepatitis, pneumonitis, thyroiditis, hypophysitis, nephritis, myocarditis. The reflex is hold the drug and give steroids, with the exception of endocrine toxicity where hormone replacement is usually what is needed. Any symptom in a patient on a checkpoint inhibitor is drug-related until proven otherwise.

Source: ESMO clinical practice guidelines — management of toxicities from immunotherapy ESMO · tier 2, specialty society or college