Immune-related adverse events-pembrolizumab-induced colitis-the importance of early diagnosis and treatment: A case report and review of the literature

Abstract

Immune Checkpoint Inhibitors (ICIs) are monoclonal antibodies that block inhibitory immune targets, such as cytotoxic T lymphocyte antigen 4 (CTLA-4), programmed cell death protein 1 (PD-1), and programmed death ligand 1 (PD-L). Pembrolizumab targets the PD-1 receptor of lymphocytes in lung cancer treatment. ICI checkpoint blockade enhances immunity against cancer cells. However, loss of immunoregulatory control can cause autoimmune reactions in various organs, leading to immune-related adverse events (irAEs). The most common irAE is ICIs-induced colitis, which usually develops 6-8 weeks after ICI initiation and can involve any part of the gastrointestinal system. Herein, we report a presentation of pembrolizumab-induced colitis in a female patient with metastatic lung cancer and review the most recent findings in the model of checkpoint-induced colitis. It was interesting to learn that the colon mucosa may show normal macroscopic findings, but microscopically, immunotherapy-induced autoimmune colitis could be present. Additionally, patients with grade 2 or higher symptoms should have a colonoscopy, receive systemic corticosteroids as treatment, and, based on their response, receive biologic therapy. Here, we present a case report of in a 45-year-old female who has been a smoker for 25 years, without comorbidities, and with metastatic lung cancer who developed colitis after the seventh cycle of pembrolizumab. This case presentation highlights the importance of early recognition and appropriate intervention in order to prevent permanent interruption of treatment with checkpoint inhibitors, as well as prevention of colitis complications.

Keywords: checkpoint inhibitor induced colitis; immune checkpoint inhibitors; immune-related adverse events; immunotherapy; non-small cell lung carcinoma; pembrolizumab.

Figure 1.

MRI of endocranium (07/23). The first and second MRI images of this figure depict an expansive frontal lesion with a diameter of 3.9 × 3.4 × 3.8 cm, surrounded by extensive perifocal vasogenic edema that exerts a compressive effect on the surrounding brain parenchyma. The third MRI image of this figure depicts a smaller cerebellar lesion on the left hemisphere of the brain.

Figure 2.

The initial MSCT of the chest (08/23) described a spiculated tumor of 28 × 31 × 29 mm on the left at the level of the anterior segment of the upper lobe.

Figure 3.

MSCT of the chest and abdomen. (a) On the left figure of the computed tomography (CT) scan (10/23) is shown iUPD (in the upper left lobe, the tumor had dimensions of 32 × 68 × 70 mm; LNs conglomerate from group 4L and 5 measured 37 × 45 × 40 mm; pericardial effusion was 14 mm). (b) On the right figure of the CT scan (01/24) is shown iSD with the tumor in the upper left lobe measuring 51 × 33 × 60 mm.

Figure 4.

Colonoscopy, demonstrating a normal macroscopic finding of the colon mucosa.

Figure 5.

Microscopic colitis interstitialis (autoimmune), mild to moderate degree: the colon’s mucosa remains intact, a mild-to-moderate diffuse inflammatory infiltrate, consisting of lymphocytes, plasma cells, and rare eosinophilic granulocytes, permeates the edematous stroma. Original magnification: (a) ×40, (b) ×100, and (c) ×200.