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Cited by 235Cancer Immunotherapy and BiomarkersInflammatory Bowel DiseasePharmacovigilance and Adverse Drug Reactions

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Vedolizumab treatment for immune checkpoint inhibitor-induced enterocolitis

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Bergqvist, Viktoria, Hertervig, Erik, Gedeon, Peter, Kopljar, Marija, Griph, Håkan, Kinhult, Sara, Carneiro, Ana, Marsal, Jan·2017·Cancer Immunology Immunotherapy
DOI 10.1007/s00262-017-1962-6PMC PMC5406433
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Abstract

Immune checkpoint inhibitors (ICPI), such as ipilimumab [anti-cytotoxic T-lymphocyte antigen-4 (CTLA-4) antibody] and nivolumab or pembrolizumab [anti-programmed cell death protein-1 (PD-1) antibodies], improve survival in several cancer types. Since inhibition of CTLA-4 or PD-1 leads to non-selective activation of the immune system, immune-related adverse events (irAEs) are frequent. Enterocolitis is a common irAE, currently managed with corticosteroids and, if necessary, anti-tumor necrosis factor-α therapy. Such a regimen carries a risk of serious side-effects including infections, and may potentially imply impaired antitumor effects. Vedolizumab is an anti-integrin α4β7 antibody with gut-specific immunosuppressive effects, approved for Crohn's disease and ulcerative colitis. We report a case series of seven patients with metastatic melanoma or lung cancer, treated with vedolizumab off-label for ipilimumab- or nivolumab-induced enterocolitis, from June 2014 through October 2016. Clinical, laboratory, endoscopic, and histologic data were analyzed. Patients initially received corticosteroids but were steroid-dependent and/or partially refractory. One patient was administered infliximab but was refractory. The median time from onset of enterocolitis to start of vedolizumab therapy was 79 days. Following vedolizumab therapy, all patients but one experienced steroid-free enterocolitis remission, with normalized fecal calprotectin. This was achieved after a median of 56 days from vedolizumab start, without any vedolizumab-related side-effects noted. The patient in whom vedolizumab was not successful, due to active ulcerative colitis, received vedolizumab prophylactically. This is the first case series to suggest that vedolizumab is an effective and well-tolerated therapeutic for steroid-dependent or partially refractory ICPI-induced enterocolitis. A larger prospective study to evaluate vedolizumab in this indication is warranted.

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Fig. 1 Evaluation of immune checkpoint inhibitor-induced enterocolitis using endoscopic scores developed for Crohn’s disease and ulcerative colitis. a Colonoscopy findings were categorized based on global endoscopic assessment (GEA) of the most inflamed segment (normal, mild, moderate, or severe inflammation), and compared to endoscopic index scores generated using the Ulcerative Colitis Endoscopic Index of Severity (UCEIS; 0–8 points) [25], Simple Endoscopic Score for Crohn’s Disease (SES-CD; 0–12 points) [26], and a combined endoscopic score (sum of individual UCEIS and SES-CD scores; 0–20 points). b Colonic mucosal histopathology was categorized into normal, mild, moderate, or severe inflammation, and compared to the combined endoscopic score. Columns and error bars represent median values ± range
Fig. 1 Evaluation of immune checkpoint inhibitor-induced enterocolitis using endoscopic scores developed for Crohn’s disease and ulcerative colitis. a Colonoscopy findings were categorized based on global endoscopic assessment (GEA) of the most inflamed segment (normal, mild, moderate, or severe inflammation), and compared to endoscopic index scores generated using the Ulcerative Colitis Endoscopic Index of Severity (UCEIS; 0–8 points) [25], Simple Endoscopic Score for Crohn’s Disease (SES-CD; 0–12 points) [26], and a combined endoscopic score (sum of individual UCEIS and SES-CD scores; 0–20 points). b Colonic mucosal histopathology was categorized into normal, mild, moderate, or severe inflammation, and compared to the combined endoscopic score. Columns and error bars represent median values ± rangeCC BY · PubMed Central
Fig. 2 Laboratory inflammatory biomarkers in patients with immune checkpoint inhibitor-induced enterocolitis, in relation to corticosteroid and vedolizumab treatment. a Plasma albumin concentrations at enterocolitis onset, during corticosteroid therapy just before starting vedolizumab, and after vedolizumab therapy. b Plasma C-reactive protein concentrations at corresponding time-points. c Fecal calprotectin concentrations at corresponding time-points. Enterocolitis onset: at onset of ICPI-induced enterocolitis, Corticosteroid therapy: just prior to initiation of vedolizumab treatment, Post vedolizumab: after vedolizumab treatment and after corticosteroids had been tapered. P plasma, F fecal, CRP C-reactive protein, ICPI immune checkpoint inhibitor. Individual values and medians; *P < 0.05 (Wilcoxon test); n = 6 (patient No. 3, who received vedolizumab prophylactically, was excluded from this analysis)
Fig. 2 Laboratory inflammatory biomarkers in patients with immune checkpoint inhibitor-induced enterocolitis, in relation to corticosteroid and vedolizumab treatment. a Plasma albumin concentrations at enterocolitis onset, during corticosteroid therapy just before starting vedolizumab, and after vedolizumab therapy. b Plasma C-reactive protein concentrations at corresponding time-points. c Fecal calprotectin concentrations at corresponding time-points. Enterocolitis onset: at onset of ICPI-induced enterocolitis, Corticosteroid therapy: just prior to initiation of vedolizumab treatment, Post vedolizumab: after vedolizumab treatment and after corticosteroids had been tapered. P plasma, F fecal, CRP C-reactive protein, ICPI immune checkpoint inhibitor. Individual values and medians; *P < 0.05 (Wilcoxon test); n = 6 (patient No. 3, who received vedolizumab prophylactically, was excluded from this analysis)CC BY · PubMed Central
Fig. 3 Blood lymphocyte and neutrophil counts in patients with immune checkpoint inhibitor-induced enterocolitis, in relation to ICPI, corticosteroid, and vedolizumab treatment. a Blood neutrophil counts before onset of enterocolitis, at enterocolitis onset, during corticosteroid therapy just before starting vedolizumab, and after vedolizumab therapy. b Blood lymphocyte counts at corresponding time-points. c The blood neutrophil/lymphocyte ratio at corresponding time-points. Individual values and medians. Blood cell counts were not available in all patients. Pre ICPI: just prior to initiation of ICPI therapy, Enterocolitis onset: at onset of ICPI-induced enterocolitis, Corticosteroid therapy: just prior to initiation of vedolizumab treatment, Post vedolizumab: after vedolizumab treatment and after corticosteroids had been tapered. B blood, ICPI immune checkpoint inhibitor, NLR neutrophil/lymphocyte ratio
Fig. 3 Blood lymphocyte and neutrophil counts in patients with immune checkpoint inhibitor-induced enterocolitis, in relation to ICPI, corticosteroid, and vedolizumab treatment. a Blood neutrophil counts before onset of enterocolitis, at enterocolitis onset, during corticosteroid therapy just before starting vedolizumab, and after vedolizumab therapy. b Blood lymphocyte counts at corresponding time-points. c The blood neutrophil/lymphocyte ratio at corresponding time-points. Individual values and medians. Blood cell counts were not available in all patients. Pre ICPI: just prior to initiation of ICPI therapy, Enterocolitis onset: at onset of ICPI-induced enterocolitis, Corticosteroid therapy: just prior to initiation of vedolizumab treatment, Post vedolizumab: after vedolizumab treatment and after corticosteroids had been tapered. B blood, ICPI immune checkpoint inhibitor, NLR neutrophil/lymphocyte ratioCC BY · PubMed Central

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Metadata

Authors
Bergqvist, V., Hertervig, E., Gedeon, P., Kopljar, M., Griph, H., Kinhult, S., Carneiro, A., & Marsal, J.
Affiliations
  • Skåne University Hospital (SE)
  • Lund University (SE)
Corresponding author
Marsal, Jan
ORCID
Venue
Cancer Immunology Immunotherapy
Publisher
Springer Science and Business Media LLC
Published
2017-02-15
Volume
66
Issue
5
Pages
581-592
ISSN
  • 0340-7004 (ISSN-L)
  • 1432-0851
DOI
10.1007/s00262-017-1962-6
PMC
PMC5406433
OpenAlex
W2588366403
Cited by
234
References
56
Citations by year
2026: 10 · 2025: 14 · 2024: 20 · 2023: 13 · 2022: 24 · 2021: 33 · 2020: 41 · 2019: 37 · 2018: 35 · 2017: 6
FWCI
14.35
Type
journal article
Language
en
Open access
Licence
Locations
  • Cancer Immunology Immunotherapy (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Lund University Publications (Lund University) (submittedVersion)
Funders
  • Hedlund Foundation
  • Alfred Österlunds Stiftelse
  • Julin Foundation
  • Kungliga Fysiografiska Sällskapet i Lund
  • Svenska Läkaresällskapet
  • Grants to researchers in the public health care from the Swedish government (ALFSKANE-539811)
  • Healthcare Region of Southern Sweden
Topics
  • Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
  • Health Sciences › Medicine › Gastroenterology › Inflammatory Bowel Disease
  • Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Toxicology › Pharmacovigilance and Adverse Drug Reactions
Keywords
vedolizumab, immune-related adverse events, ipilimumab, nivolumab, pembrolizumab, CTLA-4, PD-1, metastatic melanoma, lung cancer, off-label drug use, fecal calprotectin, ulcerative colitis
MeSH terms
Ipilimumab, Nivolumab, Adult, Aged, Antibodies, Monoclonal, Carcinoma, Non-Small-Cell Lung, Enterocolitis, Female, Gastrointestinal Agents, Humans, Lung Neoplasms, Male, Melanoma, Middle Aged, Cell Cycle Checkpoints, Antibodies, Monoclonal, Humanized

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