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Background: Immune checkpoint inhibitor (ICI) therapy can be complicated by gastrointestinal adverse events (AEs). Similarly, gastrointestinal AEs have been reported with the use of serine/threonine-protein kinase B-Raf (BRAF) and mitogen-activated protein kinase kinase (MEK) inhibitor therapy. We investigated the characteristics and management of gastrointestinal AEs related to sequential ICI and BRAF/MEK inhibitor therapy., Methods: We identified 255 adult cancer patients who received both BRAF/MEK inhibitor therapy and ICI therapy between 2014 and 2021. Thirty-two eligible patients had gastrointestinal AEs after receiving both therapies and were categorized based on the order of their administration. Their clinical characteristics, evaluation, treatment and outcomes were compared., Results: Of the 32 eligible patients, 18 (56.3%) received ICI therapy followed by BRAF/MEK inhibitors (early ICI group), and 14 (44.8%) received BRAF/MEK inhibitor therapy followed by ICI (early BRAF/MEK inhibitor group). Compared with the early BRAF/MEK inhibitor group, the early ICI group had higher rates of grade 3-4 diarrhea (50.0% vs. 14.3%, P=0.047) and grade 3-4 colitis (38.9% vs. 0%, P=0.010). The early ICI group had a later onset of colitis (347.5 vs. 84.5 days, P=0.011) and a higher rate of hospitalization at initial colitis presentation (100% vs. 71.4%, P=0.028). Patients in the early ICI group were more likely to have diarrhea or colitis recurrence (69.2% vs. 9.1%, P=0.019) and re-hospitalization for colitis (38.9% vs. 0%, P=0.010)., Conclusion: The sequential exposure of BRAF/MEK therapy after ICI may contribute to a more aggressive clinical profile of gastrointestinal toxicities that may warrant a more aggressive management strategy., Competing Interests: Conflict of Interest: Y. Wang: consulting fee for Sorriso, MabQuest, Azur Rx, (Copyright: © Hellenic Society of Gastroenterology.)

Background: Immune checkpoint inhibitors (ICI) are known to cause immune-related adverse events (irAE) with the gastrointestinal (GI) tract among the most affected. Our knowledge of GI irAE in patients with luminal GI malignancies is poor. We aimed to characterize the incidence, clinical features, treatment, and outcomes of these GI irAEs., Methods: This was a retrospective study of patients with malignancies involving the luminal GI tract and GI irAEs at MD Anderson Cancer Center from January 2010 to June 2020. Clinical data were collected and analyzed., Results: Eighteen patients with luminal GI tract malignancies treated with ICIs had evidence of GI irAEs based on clinical symptoms and/or histology. The predominant GI irAE symptom was diarrhea (78%). Ten had non-ulcerative inflammation (56%) and 5 had ulcerative inflammation (28%) on endoscopy. Histologically, 3 patients (17%) had evidence of acute inflammation, 4 (22%) had chronic inflammation, and 9 (50%) had both. Ten patients (56%) received immunosuppressant treatment, which included steroids alone (n=2, 20%), steroids with biologics (infliximab or vedolizumab) (n=7, 70%), or biologics alone (n=1, 10%), with clinical remission in all cases. Of the 6 patients who previously had stable or ICI-responsive cancer and received immunosuppressants, none developed progression of GI luminal malignancy during the study period., Conclusions: GI irAEs occurred in 2.4% of patients treated with ICI for cancer involving the luminal GI tract. Immunosuppressant therapies (e.g., vedolizumab) appear to be effective for GI irAEs, showing no association with further GI luminal cancer progression, recurrence, or a subsequent poor response to ICI therapy., Competing Interests: Conflict of Interest: None, (Copyright: © Hellenic Society of Gastroenterology.)

Background: Immune checkpoint inhibitors (ICIs), used for the treatment of solid and hematologic malignancies, come with the risk of immune-related adverse events (irAEs). Opportunistic infections (e.g., cytomegalovirus [CMV]) mimic irAE symptoms and are understudied in this population. We aimed to describe the incidence, characteristics, treatment and outcomes of CMV infection in ICI-treated patients., Methods: We conducted a single-center retrospective review of all adult patients who were CMV-positive after ICI therapy between 06/2011 and 05/2020. A CMV-positive non-ICI cohort was matched to the ICI group based on age, sex and cancer type. Variables of interest were collected through electronic medical records., Results: The study population comprised 192 patients overall. CMV infection incidence was 7.7% in ICI patients and 12.9% in non-ICI patients (P<0.001). Rates of infection clearance (83% vs. 50%, P=0.002) and recurrence (20% vs. 3%, P=0.037) were higher in ICI patients with hematologic vs. solid tumors, despite similar treatments. All-cause mortality was higher in solid rather than hematologic malignancies in ICI patients (83% vs. 54%, P=0.009); CMV-related mortality was low (3-4%) in both groups., Conclusions: CMV infection occurred in about 7.7% of the ICI-treated cancer population. The infection can be disseminated in multiple organs and has a wide spectrum of clinical symptoms. ICI-treated patients with a hematologic malignancy had higher viral clearance and recurrence than those with solid tumors. In this study, CMV itself did not lead to high mortality in cancer patients. Further study is needed to investigate the role of CMV infection in patients' irAEs and cancer outcome., Competing Interests: Conflict of Interest: None, (Copyright: © Hellenic Society of Gastroenterology.)

Background: Immune checkpoint inhibitors (ICIs) have revolutionized cancer treatment, but are associated with immune-mediated diarrhea and colitis (IMDC). Clostridioides difficile infection (CDI) can cause infectious diarrhea with overlapping symptoms. Thus, we sought to elucidate the characteristics of CDI in patients treated with ICI, in the context of IMDC., Methods: We conducted a retrospective, single-center study of adult cancer patients (N=421) with ICI exposure from 2015-2020 and a positive stool nucleic acid amplification test and/or enzyme immunoassay for CDI. Baseline characteristics, treatments, and outcomes were compared between patients with and without concurrent IMDC., Results: Forty-one eligible patients were included, 27 with concurrent IMDC and 14 without. Twenty-seven patients were taking programmed death-1 or its ligand inhibitors and 14 were taking cytotoxic T-lymphocyte-associated antigen 4 inhibitors. Patients with concurrent CDI and IMDC had a longer symptom duration (20 vs. 5 days, P=0.003) and a higher rate of grade 3-4 diarrhea (41% vs. 7%, P=0.033). Among patients with concurrent IMDC, preceding antibiotics (P=0.050) and proton pump inhibitors (PPI) (P=0.038) were used more frequently among individuals who developed CDI after immunosuppressant exposure. Thirty-eight patients received antibiotics for CDI, while 5 required fecal microbiota transplantation for concurrent CDI & IMDC., Conclusions: CDI is common in ICI-treated cancer patients, especially those with IMDC requiring immunosuppressants. Antibiotics did not alter the need for immunosuppressants in those with concurrent IMDC. Use of PPI and antibiotics while receiving immunosuppressants for IMDC was associated with a greater risk of CDI. Further large-scale studies are warranted to clarify the role of CDI, antibiotics and immunosuppression treatment in IMDC patients., Competing Interests: Conflict of Interest: P. Grivas provided consulting to AstraZeneca, Astellas Pharma, Bayer, Bristol Myers Squibb, Dyania Health, EMD Serono, Exelixis, Foundation Medicine, Genentech/Roche, Genzyme, GlaxoSmithKline, Guardant Health, Gilead Sciences, Infinity Pharmaceuticals, Janssen, Lucence Health, Merck, Mirati Therapeutics, Pfizer, QED Therapeutics, Regeneron Pharmaceuticals, Seattle Genetics, UroGen, SilverBack Therapeutics, 4D Pharma PLC. His institution has received grants from Bavarian Nordic, Bristol Myers Squibb, Clovis Oncology, Debiopharm, EMD Serono, G1 Therapeutics, Gilead Sciences, GlaxoSmithKline, Merck, Mirati Therapeutics, Pfizer, QED Therapeutics. Dr. Wang has disclosed serving as a consultant for Tillotts Pharma, and AzurRx Pharma., (Copyright: © Hellenic Society of Gastroenterology.)

Background: Limited data are available concerning the clinical features of toxic gastrointestinal (GI) effects of taxane-based therapy. We describe the clinical, endoscopic and histologic features of taxane-induced colitis., Methods: This retrospective study included cancer patients who received taxane therapy and underwent colonoscopy for GI symptoms from 2000-2018., Results: Of the 45,527 patients who received taxane therapy during the study period, 76 (0.2%) met the inclusion criteria. Most patients (54%) received paclitaxel, 37% docetaxel, and 9% nab-paclitaxel. The median time from taxane therapy initiation to colitis symptom onset was 31 days. The median duration of colitis symptoms was 30 days. Colitis treatment comprised immunosuppressive therapy in 8 patients (11%), antibiotics in 17 (22%), antimotility agents in 18 (24%), and octreotide or somatostatin in 2 (3%). Thirty-five patients (46%) required hospitalization and seven (9%) required admission to the intensive care unit (ICU). Endoscopy revealed mucosal ulceration in 19 patients (25%), nonulcerative inflammation in 32 (42%), and normal findings in 25 (33%). Seventeen patients (22%) had features of lymphocytic colitis. One patient had spontaneous colonic perforation that required surgical intervention. Colitis symptoms recurred in 7 patients (9%) after initial improvement. Patients who received nab-paclitaxel developed GI toxicity earlier (P=0.003), required colitis-related hospitalization more frequently (P=0.005), and received intravenous fluids more frequently (P=0.025), compared with patients who received other taxanes., Conclusions: Taxane-related colitis can present with significant inflammation on colonoscopy, and in a minority of patients as microscopic colitis. Taxane-induced colitis, although uncommon, can lead to ICU admission and colonic perforation., Competing Interests: Conflict of Interest: None, (Copyright: © Hellenic Society of Gastroenterology.)

Background: The risk of colorectal neoplasia in breast cancer survivors is unclear. This study aimed to determine the colonic adenoma detection rate (ADR) in patients with breast cancer., Methods: We conducted a retrospective study of patients with breast cancer who underwent a colonoscopy between 2000 and 2017. A control group (n=3295), comprising cancer-free patients undergoing their first screening colonoscopy, was used for comparison., Results: Of 62,820 breast cancer patients, 3304 met the inclusion criteria. The mean age at the time of first colonoscopy was 59 years. ADR was 55%; 1803 patients had adenomas. High-grade dysplasia was evident in 28% of polyps and invasive adenocarcinoma was detected in 172 patients (5%). The median time from breast cancer diagnosis to adenoma detection was 3 years. The ADR was 21% in patients aged <40 years (n=63) and 39% in patients aged 40-50 years (n=314). The ADR was 26% in patients <50 years with a body mass index (BMI) lower than 30 kg/m 2 or no family history of colorectal cancer. Multivariate logistic regression analysis revealed that the following independent factors were associated with a greater risk of colon adenoma: older age, higher BMI, family history of colorectal cancer, and personal history of breast cancer., Conclusions: In patients with breast cancer, the ADR was higher than the reported rates for the general population. Screening colonoscopy should be considered soon after breast cancer diagnosis in patients <50 years of age. Further prospective studies investigating our findings are warranted., Competing Interests: Conflict of Interest: None

Purpose To increase awareness, outline strategies, and offer guidance on the recommended management of immune-related adverse events in patients treated with immune checkpoint inhibitor (ICPi) therapy. Methods A multidisciplinary, multi-organizational panel of experts in medical oncology, dermatology, gastroenterology, rheumatology, pulmonology, endocrinology, urology, neurology, hematology, emergency medicine, nursing, trialist, and advocacy was convened to develop the clinical practice guideline. Guideline development involved a systematic review of the literature and an informal consensus process. The systematic review focused on guidelines, systematic reviews and meta-analyses, randomized controlled trials, and case series published from 2000 through 2017. Results The systematic review identified 204 eligible publications. Much of the evidence consisted of systematic reviews of observational data, consensus guidelines, case series, and case reports. Due to the paucity of high-quality evidence on management of immune-related adverse events, recommendations are based on expert consensus. Recommendations Recommendations for specific organ system-based toxicity diagnosis and management are presented. While management varies according to organ system affected, in general, ICPi therapy should be continued with close monitoring for grade 1 toxicities, with the exception of some neurologic, hematologic, and cardiac toxicities. ICPi therapy may be suspended for most grade 2 toxicities, with consideration of resuming when symptoms revert to grade 1 or less. Corticosteroids may be administered. Grade 3 toxicities generally warrant suspension of ICPis and the initiation of high-dose corticosteroids (prednisone 1 to 2 mg/kg/d or methylprednisolone 1 to 2 mg/kg/d). Corticosteroids should be tapered over the course of at least 4 to 6 weeks. Some refractory cases may require infliximab or other immunosuppressive therapy. In general, permanent discontinuation of ICPis is recommended with grade 4 toxicities, with the exception of endocrinopathies that have been controlled by hormone replacement. Additional information is available at www.asco.org/supportive-care-guidelines and www.asco.org/guidelineswiki .