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Ipilimumab-Induced Gastrointestinal Toxicities: A Management Algorithm

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Abstract

Ipilimumab is a cytotoxic T-lymphocyte-associated antigen-4-blocking monoclonal antibody, which has shown a significant survival benefit in metastatic melanoma patients. Despite being a promising therapy for a disease with an otherwise rather dismal prognosis, it is associated with several immune-related adverse effects (IRAE) mainly targeted toward the digestive tract, skin, liver, and hypothalamic-pituitary axis. Ipilimumab-induced gastrointestinal toxicity (IGT) include diarrhea (~44 %), colitis (~18 %), bowel perforation (<1 %), and pancreatitis (<1.5 %). Early recognition of IRAE and treatment initiation are critical to decrease the risk of further complications. Management included steroids as initial therapy, followed by infliximab (anti-tumor necrosis factor alpha antibody) and/or surgical option for complications like bowel perforation. We present a series of three patients with metastatic melanoma, who received treatment with ipilimumab, and presented with varying gastrointestinal clinical manifestations and complications. Through this case series, our attempt is to make practicing gastroenterologists cognizant about the wide spectrum of gastrointestinal toxicity of this rather new clinical entity, as well as to discuss management algorithm for IGT.

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Abbreviations

Anti-TNF:

Anti-tumor necrosis factor alpha antibody

CD:

Cluster differentiating

CTLA-4:

Cytotoxic T-lymphocyte-associated antigen-4-blocking

ESR:

Erythrocyte sedimentation rate

FDA:

Food and drug administration

GI:

Gastrointestinal

HPA:

Hypothalamic-pituitary axis

IRAE:

Immune-related adverse effects

IGT:

Ipilimumab-induced gastrointestinal toxicity

PDN:

Prednisone

QID:

Four times daily

TID:

Three times daily

NSCLC:

Non-small-cell lung cancer

RCC:

Renal cell carcinoma

IV:

Intravenous

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Author contributions

Drs. JSK and MG contributed to study concept and design, acquisition of data, analysis and interpretation of data, drafting of the manuscript, and revisions. Drs. LH and CK critically revised the manuscript for important intellectual content. Drs. FA and MGSS contributed to study concept and design, drafting of the manuscript, and critical revision of the manuscript for important intellectual content.

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Authors and Affiliations

  1. Department of Internal Medicine, University of Arkansas for Medical Sciences (UAMS), Little Rock, AR, USA

    Jagpal S. Klair, Mohit Girotra, Laura F. Hutchins, Farshad Aduli & Mauricio Garcia-Saenz-de-Sicilia

  2. Division of Hematology and Oncology, University of Arkansas for Medical Sciences (UAMS), Little Rock, AR, USA

    Laura F. Hutchins

  3. Department of Pathology, University of Arkansas for Medical Sciences (UAMS), Little Rock, AR, USA

    Kari D. Caradine

  4. Division of Gastroenterology and Hepatology, Department of Medicine, University of Arkansas for Medical Sciences (UAMS), 4301 W. Markham Street, Shorey S8/68, Slot # 567, Little Rock, AR, 72205, USA

    Mohit Girotra, Farshad Aduli & Mauricio Garcia-Saenz-de-Sicilia

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  1. Jagpal S. Klair
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Correspondence to Jagpal S. Klair.

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Jagpal S. Klair and Mohit Girotra are combined first authors.

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Klair, J.S., Girotra, M., Hutchins, L.F. et al. Ipilimumab-Induced Gastrointestinal Toxicities: A Management Algorithm. Dig Dis Sci 61, 2132–2139 (2016). https://doi.org/10.1007/s10620-016-4042-4

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  • DOI: https://doi.org/10.1007/s10620-016-4042-4

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