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Difficulty: MediumNeoplastic Processes

A 64-year-old man presents to the emergency department with a 4-day history of severe, crampy abdominal pain and 8 to 10 watery, non-bloody bowel movements daily. He was diagnosed with metastatic non-small cell lung cancer 3 months ago. Genomic testing of his tumor revealed high expression of a ligand that binds to an inhibitory T-cell receptor. Based on these findings, he recently began targeted monoclonal antibody therapy, receiving his last infusion 10 days ago. His temperature is 37.9°C (100.2°F), blood pressure is 102/65 mm Hg, and pulse is 112/min. Physical examination reveals dry mucous membranes and diffuse abdominal tenderness without rigidity, rebound, or guarding. Laboratory studies show a serum creatinine of 1.4 mg/dL (baseline 0.9 mg/dL) and a white blood cell count of 11,500/mm³. Rapid stool testing for Clostridioides difficile toxin is negative. Which of the following is the most appropriate next step in management?

  1. Initiate intravenous methylprednisolone and permanently discontinue the targeted monoclonal antibody therapyAnswer
  2. B
    Prescribe oral vancomycin and continue the current targeted therapy regimen
  3. C
    Administer loperamide and resume the monoclonal antibody therapy at a reduced dosage upon symptom resolution
  4. D
    Order an urgent magnetic resonance imaging scan of the abdomen and pelvis
  5. E
    Consult general surgery for an urgent diagnostic laparoscopy and peritoneal biopsy

Answer

Initiate intravenous methylprednisolone and permanently discontinue the targeted monoclonal antibody therapy
The correct intervention involves halting the immunotherapy permanently and administering systemic steroids. The patient's history of targeted therapy for a tumor expressing a ligand for an inhibitory T-cell receptor indicates he is taking a PD-1 or PD-L1 inhibitor. These immune checkpoint inhibitors restore T-cell-mediated anti-tumor immunity but frequently disrupt self-tolerance, causing autoimmune toxicities known as immune-related adverse events (irAEs). This patient is presenting with Grade 3 immune-mediated colitis (defined as an increase of ≥7 stools per day over baseline, or symptoms interfering with activities of daily living). Standard management for Grade 3 or 4 irAEs requires immediate hospitalization, initiation of high-dose intravenous corticosteroids (such as methylprednisolone), and permanent discontinuation of the checkpoint inhibitor.

Step-by-Step Solution

1
Identify the mechanism of the patient's antineoplastic therapy.
The tumor expresses a ligand binding to an inhibitory T-cell receptor (PD-L1), indicating the patient is receiving an immune checkpoint inhibitor (e.g., pembrolizumab or nivolumab).
Identifying the drug class is necessary to anticipate its specific, mechanism-based adverse effect profile.
2
Evaluate the clinical severity of the patient's gastrointestinal presentation.
The patient has 8 to 10 watery stools daily along with dehydration and acute kidney injury, which classifies as Grade 3 (severe) colitis.
Toxicity grading directly dictates the algorithmic management of immune-related adverse events.
3
Determine the appropriate intervention for severe immune-mediated colitis.
Administration of systemic high-dose corticosteroids and the permanent cessation of the immunotherapy.
Grade 3 and 4 immune-mediated toxicities require immediate suppression of the overactive immune response to prevent life-threatening bowel perforation or toxic megacolon.

Key Concept

Severe (Grade 3 or 4) immune-mediated colitis secondary to immune checkpoint inhibitors (e.g., PD-1/PD-L1 antagonists) requires prompt administration of systemic high-dose corticosteroids and permanent discontinuation of the offending immunotherapy agent.
Estimated Time:1m 15s
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Neoplastic Processes

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