Introduction
Immune checkpoint inhibitors (ICI) are widely used in the management of numerous solid tumors and act by enhancing T-cell–mediated anti-tumour responses. While this activation boosts the immune response against cancer cells, it may also result in immune-related side effects (irAEs). Gastrointestinal symptoms, mainly colitis and diarrhea, are among the most common irAEs.1 We have recently (February 2025) opened a dedicated clinic, within our Gastroenterology outpatient service, to manage patients who experience gastrointestinal irAEs during ICI therapy for epithelial cancers.
Aims & Methods
Our aim was to evaluate characteristics and outcomes of patients referred to our dedicated clinic for the management of gastrointestinal irAEs associated with ICI therapy since its start (February 2025). All patients were clinically evaluated and were treated with standard-of-care therapy in accordance to European Guidelines2. Patients were followed up for at least 8 weeks following initiation of therapy. We collected data on patient demographics (gender and age), patient’s overall health status as assessed by the Charlson Comorbidity Index (CCI)3, cancer type, oncological therapy, diarrhea severity (graded via CTCAE)4, time to onset of diarrhea following the initiation of oncological therapy, interruption of ICI, outcomes of colonscopy (if performed), treatment modality for ICI-related gastrointestinal toxicity, time to resolution of diarrhea (in weeks), and whether ICI therapy was subsequently resumed.
Results
We included 14 patients affected by ICI-related diarrhea or colitis (grade 1: n=2 , grade 2: n=9 , grade 3: n=2; grade 4: n=1). Four patients were affected by endometrial cancer, 3 patients melanoma, 3 lung cancer, 2 breast cancer, 1 ovarian cancer, 1 cervical cancer. Thirteen patients were treated with PD1/PDL1- inhibitors (Pembrolizumab: n=9 , Dostarlimab: n=2, Nivolumab: n=2) and one patient was treated with CTLA-4 (Ipilimumab: n=1). Ten patients interrupted immunotherapy due to ICI-related diarrhea after 17 weeks of therapy on average. As indicated by the European Guidelines2, all patients with diarrhea grade G2 or higher (6 patients) underwent colonoscopy, which revealed signs consistent with ICI-induced colitis. After standard-of-care treatment,12 patients experienced diarrhea grade 1 or lower. Mean time to resolution of diarrhea was 4.2 weeks. Among the 10 patients who had to interrupt ICI due to gastrointestinal adverse events, 5 patients (50%) resumed ICI after a mean of 4 weeks. No patients experienced any adverse events related to the standard-of-care treatment as defined by CTCAE.4
Conclusion
Despite being preliminary, our experience shows that patients managed in a dedicated clinic for gastrointestinal irAEs associated with ICI therapy experience acceptable outcomes. Future studies, aimed at comparing whether this approach is more effective than a non-dedicated management, are warranted.
References
1. Chan KK, Bass AR. Autoimmune complications of immunotherapy: pathophysiology and management. BMJ. Published online April 6, 2020:m736. doi:10.1136/bmj.m736
2. Haanen J, Obeid M, Spain L, et al. Management of toxicities from immunotherapy: ESMO Clinical Practice Guideline for diagnosis, treatment and follow-up. Ann Oncol. 2022;33(12):1217-1238. doi:10.1016/j.annonc.2022.10.001
3. Charlson ME, Pompei P, Ales KL, MacKenzie CR. A new method of classifying prognostic comorbidity in longitudinal studies: Development and validation. J Chronic Dis. 1987;40(5):373-383. doi:10.1016/0021-9681(87)90171-8
4. Freites-Martinez A, Santana N, Arias-Santiago S, Viera A. Using the Common Terminology Criteria for Adverse Events (CTCAE - Version 5.0) to Evaluate the Severity of Adverse Events of Anticancer Therapies. Actas Dermosifiliogr. 2021;112(1):90-92. doi:10.1016/j.ad.2019.05.009
Disclosure
G.I. has received personal fees for acting as speaker for Biocodex, Danone, Sofar, Malesci, Metagenics and Tillotts Pharma, and for acting as consultant and/or advisor for Ferring Therapeutics, Giuliani, Malesci and Tillotts Pharma. A.G. reports personal fees for consultancy from Eisai Srl, 3PSolutions, Real Time Meeting, Fondazione Istituto Danone, SinergieSrl, Board MRGE and Sanofi SpA personal fees for acting as a speaker for Takeda SpA, AbbVie and Sandoz SpA and personal fees for acting on advisory boards for VSL3 and Eisai. G.C. has received personal fees for acting as advisor for Ferring Therapeutics. All other authors have no conflicts of interest to disclose.
