Pembrolizumab-Induced Immune-Mediated Colitis in a Patient with Concurrent Clostridium Difficile Infection

Abstract

Pembrolizumab is a programmed death receptor-1 (PD-1) inhibitor that has been approved for treatment of a wide variety of malignancies. Immune-mediated colitis is a known but uncommon adverse effect of pembrolizumab. Symptoms of immune-mediated colitis can be similar to those of many other gastrointestinal illnesses, including Clostridium difficile infection (CDI). If not recognized and treated in a timely fashion, immune-mediated colitis can lead to significant morbidity in cancer patients. We report the case of a 56-year-old woman on pembrolizumab for metastatic non-small cell lung cancer (NSCLC) who presented with severe colitis symptoms and initially tested positive for CDI. Her colitis symptoms worsened despite appropriate treatment for CDI but later improved rapidly after systemic corticosteroid was started for suspected immune-mediated colitis. To our knowledge, this is the first reported case of concurrent pembrolizumab-induced colitis and CDI. Immune-mediated colitis should be considered in the differential diagnoses in patients on pembrolizumab or other immune checkpoint inhibitors who present with colitis symptoms, even when a concurrent infectious etiology is suspected.

British Society of Gastroenterology endorsed guidance for the management of immune checkpoint inhibitor-induced enterocolitis

“…Differential diagnoses, including infection, should be considered in the diagnostic work-up of patients with diarrhoea, even when a close temporal relationship to ICPi exposure exists. The incidence of infectious diarrhoea in ICPi-treated patients is low 14,41,58 , and even in cases where GI infection has been identified, anti-inflammatory therapy has been needed in addition to anti-microbial therapy to induce symptomatic improvement 14,41,58,59 . Clostridium difficile (C.difficile) infection should be…”

“…excluded 59 , especially in patients who have recently received antibiotics. CMV-associated colitis has been reported following ICPi-therapy, although in most patients this appears to be associated with corticosteroid-resistance and persistent/relapsing symptoms 52,54 .…”

Infections due to dysregulated immunity: an emerging complication of cancer immunotherapy

“… 102 Additionally, CDI preceding irAE colitis has been reported. 103 104 Inflammatory bowel disease can present with CDI, even in the absence of immunosuppression, 105 suggesting that excessive inflammation can favour CDI. Given the similar pathophysiology in IBD and irAE colitis, 106 there may be a subset of patients that develop CDI because of the acquired hyperinflammatory state.…”

First line Immunotherapy for Non-Small Cell Lung Cancer

“…Most common adverse reactions in patients treated with Pembrolizumab as a single agent are fatigue, musculoskeletal pain, decreased appetite, pruritus, diarrhea, nausea, rash, pyrexia, cough, dyspnea, constipation, and abdominal pain [30][31][32][33]. Immune-mediated side effects were reported and includes pneumonitis [34], colitis [35,36], hepatitis [37,38], adrenal insufficiency [39,40], hypophysitis [39], hyperthyroidism [41] and hypothyroidism [42,43], type 1 diabetes mellitus [44,45], and nephritis [46,47].…”