https://orcid.org/0000-0003-1317-183X
To the Editors,
Immune checkpoint inhibitors (ICIs) have revolutionized the treatment of metastatic malignancies1,2; ICIs target immune checkpoints such as cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4), programmed cell death 1 (PD-1), and programmed death-ligand 1 (PD-L1), thereby allowing T lymphocytes to kill cancer cells. Given their mechanisms of action, ICIs can trigger various organ-specific immune-related adverse events, including colitis.3,4 We successful used fecal microbiota transplantation (FMT) to treat a patient with severe ICI-induced colitis that was refractory to steroid and infliximab (IFX) therapy.
A 64-year-old man, diagnosed with left lung squamous cell carcinoma in 2020 (Figure 1A) and treated with bevacizumab, paclitaxel, and cisplatin, presented 6 months later with recurrent stage 4, T2N1M1 metastatic disease involving the brain, spleen, adrenal glands, and pancreas (Figures 1B, C). Tislelizumab, an anti-PD-1 ICI, was started. Two months after starting tislelizumab, the patient developed severe bloody diarrhea (>20 times/day) and abdominal pain, and tislelizumab was discontinued. Stool culture and Clostridium difficile toxin were negative. Subsequent laboratory findings revealed significant increases in white blood cells (WBCs, 11.24×109/L), C-Reactive Protein (CRP, 56.9mg/L), interleukin-6 (IL-6, 54.66 pg/mL), IL-10 (9.37 pg/mL), and fecal calprotectin (FC >1800 μg/g). Albumin (ALB, 24.8g/L) and hemoglobin (Hb, 93g/L) were significantly decreased. Colonoscopy revealed moderate mucosal inflammation with no ulceration, consistent with Mayo endoscopic subscore of 2 (Figures 1D-F). Intestinal histopathology suggested infiltration of a large number of chronic inflammatory cells such as lymphocytes (Figures 1H, I). There was no evidence of vasculitis, fungal elements, or viral staining for CMV or adenovirus. The abdominal contrast-enhanced computed tomography (CT) showed that there was thickened intestinal wall in the colorectum (Figure 1G).
A, Lung CT showed left lung space-occupying lesions. B, Brain CT showed brain space-occupying lesion.; C, Abdominal CT showed spleen, adrenal glands, and pancreas space-occupying lesions. D-F, Colonoscopic findings when the symptoms were most severe. G, Abdominal CT showed thickened intestinal wall in colorectum. H, I, Pathological image of colon.
The patient was diagnosed with grade 3 ICI-induced colitis and was started on 80mg of intravenous methylprednisolone daily. Due to persistent bloody diarrhea and abdominal pain, he received 5mg/kg of IFX at week 0, 2, and 6 and was started on oral prednisone taper. The patient’s abdominal pain significantly improved, but bloody diarrhea still persisted (>20 times/day). Multiple repeat stool cultures and C. difficile toxin assays were negative. The patient then underwent FMT. Two days after the 3 occasions of FMT therapy by nasojejunal tube (150mL fecal slurry each time), the patient had a dramatic improvement in symptoms and remained diarrhea-free at his 3-month follow-up. Laboratory findings correlated with the patient’s clinical improvement: WBC 8.43×109/L, CRP 6.4mg/L, FC 287 μg/g, ALB 38.4g/L, and Hb 113g/L.
Author Contributions
C.D. and W.X.L. had the original idea for the article and guided treatment and management of the patient. C.D. wrote the article and incorporated the comments from W.X.L. All authors reviewed and approved the final draft of the article.
Funding
None.
Conflicts of Interest
The authors declare no conflicts of interest.
Data Availability
The data underlying this article are available in the article.
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