1184 Clinical outcomes in patients with endoscopically proven immune checkpoint inhibitor-induced colitis – a multi-centre retrospective study

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Background Checkpoint inhibitor-induced colitis (CPI-c) is the second most common toxicity from immune checkpoint blockade, conferring significant morbidity and a high burden of immunosuppressive therapy.1 The impact of endoscopically evident inflammation (macroscopic inflammation, MacI) compared to histological changes only (microscopic inflammation, MicI) on outcomes is unclear.2 Methods We retrospectively analysed consecutive patients treated at two UK centres between 2014 and 2023. Inclusion criteria mandated presence of diarrhoea plus endoscopic and/or histological colonic inflammation. Statistical analyses included chi-squared test, Mann-Whitney test, and logistic regression. Results 161 patients were included; 55% male, median age 64. Cancers included melanoma (50%), kidney (18%), lung (16%). Regimes included anti-PD-(L)1 monotherapy (41%), dual anti-CTLA-4/PD-1 (47%), chemoimmunotherapy combinations (6%). 45% of patients had CTCAE G3 diarrhoea. 63% of all patients required hospitalisation. 57% had mild endoscopic inflammation (Mayo score 1), 12% had a score of 2 and 7% had severe inflammation (Mayo 3); 24% had normal mucosa (Mayo 0). 89 patients (54%) were refractory to systemic steroids and were treated with biologics (infliximab (IFX), 73; vedolizumab, 13). 41/73 (56%) responded to IFX, and 5/13 (38%) to vedolizumab. Three underwent colectomy for refractory colitis. There were no G5 events. Median time to resolution was 42 days. 30% of patients received CPI rechallenge (CPI-c was G1-2 in 55% of these); 13/45 (29%) had colitis relapse after CPI rechallenge (no relapse had higher grade than index case; G3 in 18%). 16 (9%) experienced biopsy-proven CMV colitis on follow-up and received antivirals. This was associated with CPI-c endoscopic severity (Mayo score ≥2 in 38% vs 16%, p = 0.02) and steroid-refractory CPI-c (86% vs. 52%, p = 0.01). MacI patients had CTCAE G3+ diarrhoea in 47%, micI in 42% (p = 0.56). In multivariable logistic regression, male sex (OR 3.25, p < 0.01) and dual anti-CTLA-4/PD-1 (OR 2.63, p < 0.01) predicted MacI. CTCAE grade, diarrhoea duration, emergent CMV colitis, corticosteroid therapy duration, hospitalisation, or CPI-c recurrence did not predict endoscopic phenotype. However, MacI was associated with higher faecal calprotectin (FC) levels (889 vs 414, p = 0.02) and need to escalate to biologic therapy (52.7% vs 30.6%, p < 0.05). Conclusions This represents one of the largest robustly defined real-world cohorts of patients with CPI-c. Steroid refractoriness and CMV colitis were somewhat more frequent than in the literature to date.3–5Compared to MicI, MacI is associated with a more aggressive course, marked by higher FC and requirement for biologic therapy escalation. References Haanen J, Obeid M, Spain L, et al. Management of toxicities from immunotherapy: ESMO clinical practice guideline for diagnosis, treatment and follow-up. Annals of Oncology. 2022;33(12):1217–1238. doi:10.1016/j.annonc.2022.10.001. Favara DM, Spain L, Au L, et al. Five-year review of corticosteroid duration and complications in the management of immune checkpoint inhibitor-related diarrhoea and colitis in advanced melanoma. ESMO Open. 2020;5(4). doi:10.1136/esmoopen-2019-000585. Wang Y, Abu-Sbeih H, Mao E, et al. Immune-checkpoint inhibitor-induced diarrhea and colitis in patients with advanced malignancies: retrospective review at MD anderson. Journal for ImmunoTherapy of Cancer. 2018;6(1). doi:10.1186/s40425-018-0346-6. Tay KH, Slavin MA, Thursky KA, et al. Cytomegalovirus dnaemia and disease: current‐era epidemiology, clinical characteristics and outcomes in cancer patients other than allogeneic haemopoietic transplantation. Internal Medicine Journal. 2022;52(10):1759–1767. doi:10.1111/imj.15496. Ding M, Zhang X, Wang J, et al. Treatment and outcomes of immune checkpoint inhibitors-associated colitis/diarrhea: a systematic review and meta-analysis. Digestive and Liver Disease. 2023;55(12):1621–1631. doi:10.1016/j.dld.2023.02.016. Ethics Approval This study was approved by the Royal Marsden Hospital Committee for Clinical Research as Service Evaluation ref. 1322.

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