Severe Immune-Related Enteritis after In Utero Exposure to Pembrolizumab

• Published in: The New England journal of medicine Vol. 389; no. 19; pp. 1790 - 1796
• Main Authors: Baarslag, Manuel A., Heimovaara, Joosje H., Borgers, Jessica S.W., van Aerde, Koen J., Koenen, Hans J.P.M., Smeets, Ruben L., Buitelaar, Pauline L.M., Pluim, Dick, Vos, Shoko, Henriet, Stefanie S.V., de Groot, Jan Willem B., van Grotel, Martine, Rosing, Hilde, Beijnen, Jos H., Huitema, Alwin D.R., Haanen, John B.A.G., Amant, Frédéric, Gierenz, Nicole
• Format: Journal Article
• Language: English
• Published: United States Massachusetts Medical Society 09.11.2023
• Series: Brief Report
• Subjects: Abdomen; Allergy; Antibodies, Monoclonal, Humanized - administration & dosage; Antibodies, Monoclonal, Humanized - adverse effects; Antibodies, Monoclonal, Humanized - therapeutic use; Antineoplastic Agents, Immunological - administration & dosage; Antineoplastic Agents, Immunological - adverse effects; Antineoplastic Agents, Immunological - therapeutic use; Apoptosis; Atrophy; Autoimmune Disease; Autoimmune diseases; Case reports; Cell death; Complications of Pregnancy; Diarrhea; Diarrhea, Infantile - chemically induced; Diarrhea, Infantile - immunology; Enteral nutrition; Enteritis; Enteritis - chemically induced; Enteritis - diagnosis; Enteritis - drug therapy; Enteritis - immunology; Enterocolitis - chemically induced; Enterocolitis - diagnosis; Enterocolitis - drug therapy; Enterocolitis - immunology; Failure to Thrive - chemically induced; Failure to Thrive - immunology; Gastroenteritis - chemically induced; Gastroenteritis - diagnosis; Gastroenteritis - drug therapy; Gastroenteritis - immunology; Gastroenterology; Gynecology; Gynecology General; Hematology; Hormones; Humans; Immune checkpoint inhibitors; Immune Checkpoint Inhibitors - administration & dosage; Immune Checkpoint Inhibitors - adverse effects; Immune Checkpoint Inhibitors - therapeutic use; Immunology; Immunotherapy; Infant; Infants; Inflammation; Inflammatory Bowel Disease; Infliximab; Intrauterine exposure; Lymphocytes; Melanoma; Metastases; Monoclonal antibodies; Neonatology; Neoplasms - drug therapy; Nutrition; Obstetrics; Oncology; Parenteral nutrition; Patients; PD-1 protein; Pediatrics; Pembrolizumab; Prednisolone; Pregnancy; Programmed Cell Death 1 Receptor - immunology; Small intestine; Targeted cancer therapy; Thyroid gland; Treatments in Oncology; Tumor necrosis factor-α
• ISSN: 0028-4793; 1533-4406
• DOI: 10.1056/NEJMoa2308135

Immune checkpoint blockade has become standard treatment for many types of cancer. Such therapy is indicated most often in patients with advanced or metastatic disease but has been increasingly used as adjuvant therapy in those with early-stage disease. Adverse events include immune-related organ inflammation resembling autoimmune diseases. We describe a case of severe immune-related gastroenterocolitis in a 4-month-old infant who presented with intractable diarrhea and failure to thrive after in utero exposure to pembrolizumab. Known causes of the symptoms were ruled out, and the diagnosis of pembrolizumab-induced immune-related gastroenterocolitis was supported by the results of histopathological assays, immunophenotyping, and analysis of the level of antibodies against programmed cell death protein 1 (PD-1). The infant’s condition was successfully treated with prednisolone and infliximab. After a pregnant woman with melanoma received pembrolizumab therapy, severe autoimmune enteritis developed in her healthy newborn infant. The condition was treated with prednisolone and infliximab.