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Vedolizumab treatment for immune checkpoint inhibitor-induced enterocolitis

Bergqvist, Viktoria; Hertervig, Erik LU ; Gedeon, Peter; Kopljar, Marija; Griph, Håkan; Kinhult, Sara LU ; Carneiro, Ana LU and Marsal, Jan LU (2017) In Cancer Immunology and Immunotherapy 66(5). p.581-592
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... (More)

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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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Immune-checkpoint inhibitor induced enterocolitis, Ipilimumab, Lung cancer, Melanoma, Nivolumab, Vedolizumab treatment against irAEs
in
Cancer Immunology and Immunotherapy
volume
66
issue
5
pages
581 - 592
publisher
Springer
external identifiers
  • scopus:85012893091
  • wos:000401149500004
ISSN
0340-7004
DOI
10.1007/s00262-017-1962-6
language
English
LU publication?
yes
id
86bd2df1-d108-411a-bb94-81fa53d36c8f
date added to LUP
2017-02-27 12:14:04
date last changed
2018-01-07 11:52:52
@article{86bd2df1-d108-411a-bb94-81fa53d36c8f,
  abstract     = {<p>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.</p>},
  author       = {Bergqvist, Viktoria and Hertervig, Erik and Gedeon, Peter and Kopljar, Marija and Griph, Håkan and Kinhult, Sara and Carneiro, Ana and Marsal, Jan},
  issn         = {0340-7004},
  keyword      = {Immune-checkpoint inhibitor induced enterocolitis,Ipilimumab,Lung cancer,Melanoma,Nivolumab,Vedolizumab treatment against irAEs},
  language     = {eng},
  month        = {02},
  number       = {5},
  pages        = {581--592},
  publisher    = {Springer},
  series       = {Cancer Immunology and Immunotherapy},
  title        = {Vedolizumab treatment for immune checkpoint inhibitor-induced enterocolitis},
  url          = {http://dx.doi.org/10.1007/s00262-017-1962-6},
  volume       = {66},
  year         = {2017},
}