Gastrointestinal and liver immune-related adverse effects induced by immune checkpoint inhibitors: A descriptive observational study. / Efectos adversos inmunomediados gastrointestinales y hepáticos inducidos por los inhibidores del punto de control inmunitario: estudio descriptivo observacional.

INTRODUCTION: Immune checkpoint inhibitors (ICIs) are effective agents against several malignancies. However, they are associated with gastrointestinal and liver immune-related adverse events (GI-IrAEs and LI-IrAEs), which can lead to their temporary or permanent discontinuation. AIM: The aim of this study was to evaluate the efficacy and gastrointestinal and liver toxicity of ICIs in oncological treatments in actual clinical practice. MATERIAL AND METHODS: Patients with advanced cancer who received at least 1ICI dose between May 2015 and September 2018 were retrospectively assessed. RESULTS: 132 patients with non-small cell lung cancer (65.15%, n=86); melanoma (22.7%, n=30); renal carcinoma (9.09%, n=12); and other tumours (3%, n=4) were included. The treatments administered were nivolumab (n=82), pembrolizumab (n=28), atezolizumab (n=13), durvalumab (n=2), ipilimumab (n=1) and the antiCTLA-4/PD-1 combination (n=6). In total, 51 patients (38.6%) developed IrAEs, 17 (12.9%) of which experienced GI-IrAEs. Of these, 8 (47%) needed steroids and 1patient required surgery due to intestinal perforation. Grade I Li-IrAEs were observed in 4 patients (3.03%): 2 (50%) required corticosteroids and 1 patient had to discontinue treatment. Four patients (66.6%) who received combination therapy experienced GI-IrAEs. IrAE incidence were not associated with age, gender or drug response. CONCLUSIONS: GI-IrAEs are one of the most common adverse events in patients receiving ICIs. A multidisciplinary approach and a greater understanding of these events could help to reduce morbidity and therapy discontinuation.

Efectos adversos inmunomediados gastrointestinales y hepáticos inducidos por los inhibidores del punto de control inmunitario: estudio descriptivo observacional / Gastrointestinal and liver immune-related adverse effects induced by immune checkpoint inhibitors: A descriptive observational study

Introducción: Los inhibidores del punto de control inmunitario (immune checkpoint inhibitors [ICI]) son fármacos eficaces en el tratamiento de diversas neoplasias. Sin embargo, se han relacionado con eventos adversos inmunomediados (EAI) gastrointestinales y hepáticos que pueden desencadenar su interrupción temporal o definitiva. Objetivo: Evaluar, en condiciones de práctica real, la eficacia y la toxicidad gastrointestinal y hepática de los ICI en tratamientos oncológicos. Material y métodos: Estudio retrospectivo con inclusión de pacientes con diagnóstico de neoplasia avanzada que habían recibido al menos una dosis de ICI entre mayo de 2015 y septiembre de 2018. Resultados: Se incluyeron 132 pacientes con neoplasia de pulmón no microcítico (65,15%, n=86), melanoma (22,7%, n=30), carcinoma renal (9,09%, n=12) y otros tumores (3%, n=4). Los fármacos empleados fueron nivolumab (n=82), pembrolizumab (n=28), atezolizumab (n=13), durvalumab (n=2), ipilimumab (n=1) y la combinación anti-CTLA-4/PD-1 (n=6). El 38,6% (n=51) desarrollaron EAI, de tipo gastrointestinal en el 12,9% (n=17). De ellos, el 47% (n=8) requirieron esteroides, y un paciente precisó cirugía por perforación intestinal. En el 3,03% (n=4) se objetivaron EAI hepáticos gradoI: el 50% (n=2) requirieron corticoterapia y en un paciente fue preciso interrumpir el tratamiento. Entre los pacientes con tratamiento combinado, el 66,6% (n=4) presentaron EAI gastrointestinales. La incidencia de EAI no se relacionó con la edad, ni con el sexo, ni con la respuesta al fármaco empleado. Conclusiones: Los EAI gastrointestinales figuran entre los más frecuentemente observados en pacientes en tratamiento con ICI. El manejo multidisciplinar y un mayor conocimiento de dichos eventos podrían ayudarnos a reducir su morbilidad, así como las interrupciones del tratamiento.(AU)

Introduction: Immune checkpoint inhibitors (ICIs) are effective agents against several malignancies. However, they are associated with gastrointestinal and liver immune-related adverse events (GI-IrAEs and LI-IrAEs), which can lead to their temporary or permanent discontinuation. Aim: The aim of this study was to evaluate the efficacy and gastrointestinal and liver toxicity of ICIs in oncological treatments in actual clinical practice. Material and methods: Patients with advanced cancer who received at least 1ICI dose between May 2015 and September 2018 were retrospectively assessed. Results: 132 patients with non-small cell lung cancer (65.15%, n=86); melanoma (22.7%, n=30); renal carcinoma (9.09%, n=12); and other tumours (3%, n=4) were included. The treatments administered were nivolumab (n=82), pembrolizumab (n=28), atezolizumab (n=13), durvalumab (n=2), ipilimumab (n=1) and the antiCTLA-4/PD-1 combination (n=6). In total, 51 patients (38.6%) developed IrAEs, 17 (12.9%) of which experienced GI-IrAEs. Of these, 8 (47%) needed steroids and 1patient required surgery due to intestinal perforation. Grade I Li-IrAEs were observed in 4 patients (3.03%): 2 (50%) required corticosteroids and 1 patient had to discontinue treatment. Four patients (66.6%) who received combination therapy experienced GI-IrAEs. IrAE incidence were not associated with age, gender or drug response. Conclusions: GI-IrAEs are one of the most common adverse events in patients receiving ICIs. A multidisciplinary approach and a greater understanding of these events could help to reduce morbidity and therapy discontinuation.(AU)