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

<h3>Background</h3> 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 <h3>Methods</h3> 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. <h3>Results</h3> 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 &lt; 0.01) and dual anti-CTLA-4/PD-1 (OR 2.63, p &lt; 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 &lt; 0.05). <h3>Conclusions</h3> 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. <h3>References</h3> Haanen J, Obeid M, Spain L, <i>et al</i>. Management of toxicities from immunotherapy: ESMO clinical practice guideline for diagnosis, treatment and follow-up. <i>Annals of Oncology</i>. 2022;<b>33</b>(12):1217–1238. doi:10.1016/j.annonc.2022.10.001. Favara DM, Spain L, Au L, <i>et al</i>. Five-year review of corticosteroid duration and complications in the management of immune checkpoint inhibitor-related diarrhoea and colitis in advanced melanoma. <i>ESMO Open</i>. 2020;<b>5</b>(4). doi:10.1136/esmoopen-2019-000585. Wang Y, Abu-Sbeih H, Mao E, <i>et al</i>. Immune-checkpoint inhibitor-induced diarrhea and colitis in patients with advanced malignancies: retrospective review at MD anderson. <i>Journal for ImmunoTherapy of Cancer</i>. 2018;<b>6</b>(1). doi:10.1186/s40425-018-0346-6. Tay KH, Slavin MA, Thursky KA, <i>et al</i>. Cytomegalovirus dnaemia and disease: current‐era epidemiology, clinical characteristics and outcomes in cancer patients other than allogeneic haemopoietic transplantation.<i> Internal Medicine Journal</i>. 2022;<b>52</b>(10):1759–1767. doi:10.1111/imj.15496. Ding M, Zhang X, Wang J, <i>et al</i>. Treatment and outcomes of immune checkpoint inhibitors-associated colitis/diarrhea: a systematic review and meta-analysis. <i>Digestive and Liver Disease</i>. 2023;<b>55</b>(12):1621–1631. doi:10.1016/j.dld.2023.02.016. <h3>Ethics Approval</h3> This study was approved by the Royal Marsden Hospital Committee for Clinical Research as Service Evaluation ref. 1322.