Combination therapy consisted of nivolumab (3 mg/kg or 240 mg/body) and ipilimumab (3 mg/kg) every 3 wk for four cycles. and prognosis in non-small cell lung malignancy (LC) and malignant melanoma (MM). Kaplan-Meier analysis was used to compare the median overall survival (OS). Multivariate Cox proportional hazards models were used to identify prognostic factors. A = 0.035). In contrast, in 209 patients with non-small cell LC, there was no significant difference in OS between the groups. The multivariate analyses showed that a overall performance status of 2-3 (hazard ratio: 2.406; 95% confidence interval: 1.125C5.147; = 0.024) was an independent predictive factor for OS in patients with MM. CONCLUSION Patients receiving anti-CTLA-4 antibodies develop GI-irAEs more frequently and with higher severity than those receiving anti-PD-1/PD-L1 antibodies. Continuing ICI treatment in patients with MM with GI-irAEs have better OS. nivolumab, pembrolizumab, atezolizumab, avelumab, durvalumab, or ipilimumab) for numerous cancers [lung malignancy (LC), malignant melanoma (MM), gastric malignancy (GC), renal cell carcinoma (RCC), head and neck cancer, urothelial malignancy, gynecological malignancy, breast malignancy, or colorectal malignancy] at the Nagoya University or college Hospital from September 2014 to August 2020. Patients who received ICIs as maintenance therapy after curative chemoradiation for non-small cell lung (NSCLC) or postoperative adjuvant therapy for MM were excluded from your prognostic analysis. The background of the patients, presence or absence of irAEs, time of onset, clinical characteristics at the time of onset, and laboratory findings were collected and examined using medical records. Eligible patients were those treated with ICIs at standard doses. Nivolumab was administered at 3 mg/kg or 240 mg/body every 2 wk. However, some MM patients were administered 2 mg/kg nivolumab every 3 wk. Pembrolizumab was administered at 2 mg/kg or 200 mg/body every 3 wk. Atezolizumab was administered at 1200 mg/body every 3 wk. Avelumab was administered at 10 mg/kg every 2 wk. Durvalumab was administered at Telmisartan 10 mg/kg every 2 wk. Ipilimumab was administered at 3 mg/kg every 3 wk for four Telmisartan cycles. Combination therapy consisted of nivolumab (3 mg/kg or 240 mg/body) and ipilimumab (3 mg/kg) every 3 wk for four cycles. GI-irAEs were defined as diarrhea or bloody stools after ICI administration in patients in whom infectious enteritis could be excluded. Infectious enteritis (test was utilized for continuous variables and Fishers exact test was utilized for categorical variables. The KaplanCMeier method and log-rank assessments were used to compare the cumulative incidence and median OS among the groups. Univariate and multivariate Cox proportional hazards models were used to identify prognostic factors associated with GI-irAEs. SPSS Statistics software (version 27.0; IBM Corp., Armonk, NY, United States) was utilized for analysis. For all those analyses, a = 0.039). There were no significant differences in sex, body mass index (BMI), or Eastern Cooperative Oncology Group overall performance status (ECOG PS) between the groups. The PD-1/PD-L1 group included patients with LC, MM, RCC, GC, and other cancers (head and neck malignancy, urothelial malignancy, gynecological malignancy, breast malignancy, and colorectal malignancy); the CTLA-4 group included patients with MM and RCC. Table 1 Clinical characteristics of all patients in the programmed cell death-1/programmed death-ligand 1 and cytotoxic T-lymphocyte antigen 4 groups = 605 = 56 n(%)0.228Male419 (69.3)34 (60.7)Female186 (30.7)22 (39.3)BMI, kg/m221.3 (12.0-37.0)21.6 (13.9-43.0)0.532ECOG PS, = 0.008). We compared the cumulative incidence of GI-irAEs in the PD-1/PD-L1 group with that in the CTLA-4 group for all those cancers (Physique ?(Figure1).1). The cumulative incidence was significantly higher in the CTLA-4 group than in the PD-1/PD-L1 group (= CORIN 0.003). The median observation periods until the development of GI-irAEs were 1683.1 28.3 d [95% confidence interval (CI): 1627.6-1738.5] in the PD-1/PD-L1 Telmisartan group and 1299.7 77.7 d (95%CI: 1147.5-1452.0) in the CTLA-4 group. Open in a separate window Physique 1 KaplanCMeier curves of the cumulative incidence of gastrointestinal- immune-related adverse events for all those patients in the programmed cell death-1/programmed death-ligand 1 and cytotoxic T-lymphocyte antigen 4 groups. The cumulative incidence was significantly higher in the cytotoxic T-lymphocyte antigen 4 group than in the programmed cell death-1/programmed death-ligand 1 group (= 0.003). CTLA-4: Cytotoxic T-lymphocyte antigen 4; PD-1: Programmed cell death-1; PD-L1: Programmed death-ligand 1. Severity of GI-irAEs The clinical characteristics of patients with GI-irAEs in the PD-1/PD-L1 and CTLA-4 groups are shown in Table ?Table2.2. There were no differences in age, sex, or median ICI period before the development of GI-irAEs between the groups. In the PD-1/PD-L1 group, nine patients (26%) had Grade 1 GI-irAEs, 18 (53%) experienced Grade 2 GI-irAEs, and seven (21%) experienced Grade 3 GI-irAEs. In the CTLA-4 group,.