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Cancer Immunol Immunother. 2017 May;66(5):581-592. doi: 10.1007/s00262-017-1962-6. Epub 2017 Feb 15.

Vedolizumab treatment for immune checkpoint inhibitor-induced enterocolitis.

Author information

1
Department of Gastroenterology, Skane University Hospital, 22185, Lund, Sweden.
2
Section of Medicine, Department of Clinical Sciences, Lund University, Lund, Sweden.
3
Department of Respiratory Medicine, Skane University Hospital, Lund, Sweden.
4
Department of Oncology, Skane University Hospital, Lund, Sweden.
5
Division of Oncology and Pathology, Department of Clinical Sciences, Lund University, Lund, Sweden.
6
Department of Gastroenterology, Skane University Hospital, 22185, Lund, Sweden. jan.marsal@med.lu.se.
7
Immunology Section, Department of Experimental Medical Science, Lund University, Lund, Sweden. jan.marsal@med.lu.se.
8
Section of Medicine, Department of Clinical Sciences, Lund University, Lund, Sweden. jan.marsal@med.lu.se.

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.

KEYWORDS:

Immune-checkpoint inhibitor induced enterocolitis; Ipilimumab; Lung cancer; Melanoma; Nivolumab; Vedolizumab treatment against irAEs

PMID:
28204866
PMCID:
PMC5406433
DOI:
10.1007/s00262-017-1962-6
[Indexed for MEDLINE]
Free PMC Article

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