Severe Immune-Related Enteritis after In Utero Exposure to Pembrolizumab

Manuel A Baarslag; Joosje H Heimovaara; Jessica S W Borgers; Koen J van Aerde; Hans J P M Koenen; Ruben L Smeets; Pauline L M Buitelaar; Dick Pluim; Shoko Vos; Stefanie S V Henriet; Jan Willem B de Groot; Martine van Grotel; Hilde Rosing; Jos H Beijnen; Alwin D R Huitema; John B A G Haanen; Frédéric Amant; Nicole Gierenz

doi:10.1056/NEJMoa2308135

Severe Immune-Related Enteritis after In Utero Exposure to Pembrolizumab

N Engl J Med. 2023 Nov 9;389(19):1790-1796. doi: 10.1056/NEJMoa2308135.

Authors

Manuel A Baarslag¹, Joosje H Heimovaara¹, Jessica S W Borgers¹, Koen J van Aerde¹, Hans J P M Koenen¹, Ruben L Smeets¹, Pauline L M Buitelaar¹, Dick Pluim¹, Shoko Vos¹, Stefanie S V Henriet¹, Jan Willem B de Groot¹, Martine van Grotel¹, Hilde Rosing¹, Jos H Beijnen¹, Alwin D R Huitema¹, John B A G Haanen¹, Frédéric Amant¹, Nicole Gierenz¹

Affiliation

¹ From the Departments of Pediatrics (M.A.B.), Pediatric Infectious Diseases and Immunology (K.J.A., S.S.V.H.), Pathology (S.V.), and Pediatric Gastroenterology and Hepatology (N.G.), Amalia Children's Hospital, and the Department of Laboratory Medicine, Laboratory Medical Immunology (H.J.P.M.K., R.L.S.), and the Radboudumc Laboratory for Diagnostics (R.L.S.), Radboud University Medical Center, Nijmegen, the Departments of Gynecologic Oncology (J.H.H., F.A.), Medical Oncology (J.S.W.B., J.B.A.G.H.), Pharmacy and Pharmacology (P.L.M.B., H.R., J.H.B., A.D.R.H.), and Pharmacology (D.P.), Antoni van Leeuwenhoek-Netherlands Cancer Institute, Amsterdam, the Department of Medical Oncology, Isala Hospital, Zwolle (J.W.B.G.), the Departments of Pediatric Oncology (M.G.) and Pharmacology (A.D.R.H.), Princess Máxima Center for Pediatric Oncology, and the Departments of Pharmaceutical Sciences (J.H.B.) and Clinical Pharmacy (A.D.R.H.), University Medical Center Utrecht, Utrecht University, Utrecht - all in the Netherlands; and the Department of Oncology, Katholieke Universiteit Leuven (J.H.H., F.A.), and the Division of Gynecologic Oncology, Universitair Ziekenhuis Leuven (F.A.) - both in Leuven, Belgium.

PMID: 37937778
DOI: 10.1056/NEJMoa2308135

Abstract

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.

Publication types

Case Reports

MeSH terms

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
Diarrhea, Infantile / chemically induced
Diarrhea, Infantile / immunology
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
Humans
Immune Checkpoint Inhibitors* / administration & dosage
Immune Checkpoint Inhibitors* / adverse effects
Immune Checkpoint Inhibitors* / therapeutic use
Infant
Neoplasms* / drug therapy
Programmed Cell Death 1 Receptor / immunology

Substances

Antibodies, Monoclonal, Humanized
pembrolizumab
Antineoplastic Agents, Immunological
Immune Checkpoint Inhibitors
PDCD1 protein, human
Programmed Cell Death 1 Receptor