Outcomes of vedolizumab therapy in patients with immune checkpoint inhibitor–induced colitis: a multi-center study

Abstract

BackgroundImmune-mediated diarrhea and colitis (IMDC) can limit immune checkpoint inhibitors (ICIs) treatment, which is efficacious for advanced malignancies. Steroids and infliximab are commonly used to treat it. These agents induce systemic immunosuppression, with its associated morbidity. We assessed clinical outcomes of vedolizumab as an alternative treatment for IMDC.MethodsWe analyzed a retrospective case series of adults who had IMDC refractory to steroids and/or infliximab and received vedolizumab from 12/2016 through 04/2018.ResultsTwenty-eight patients were included. The median time from ICI therapy to IMDC onset was 10 weeks. Fifteen patients (54%) had grade 2 and 13 (46%) had grade 3 or 4 IMDC. Mucosal ulceration was present in 8 patients (29%), and nonulcerative inflammation was present in 13 (46%). All patients had features of active histologic inflammation; 14 (50%) had features of chronicity, and 10 (36%) had features of microscopic colitis concurrently. The mean duration of steroid therapy was 96 days (standard deviation 74 days). Nine patients received infliximab in addition to steroids and their IMDC was refractory to it. Among these, the duration of steroid use was 131 days compared with 85 days in patients who did not receive infliximab. Likewise, patients who failed infliximab before vedolizumab had a clinical success rate of 67% compared to 95% for patients that did not receive infliximab. The median number of vedolizumab infusions was 3 (interquartile range 1–4). The mean duration of follow-up was 15 months. Twenty-four patients (86%) achieved and sustained clinical remission. Repeat endoscopic evaluation was performed in 17 patients. Endoscopic remission was attained in 7 (54%) of the 13 patients who had abnormal endoscopic findings initially; 5/17 patients (29%) reached histologic remission as well.ConclusionsVedolizumab can be appropriate for the treatment of steroid-refractory IMDC, with favorable outcomes and a good safety profile.Electronic supplementary materialThe online version of this article (10.1186/s40425-018-0461-4) contains supplementary material, which is available to authorized users.

Adverse Events Following Cancer Immunotherapy: Obstacles and Opportunities

“…This approach may be useful for irAEs associated with the gut or skin, each of which have a unique set of chemokine receptors, selectins, and/or integrins that are involved in homing of T cells into a specific organ (integrin α4β7 and chemokine receptor CCR9 for the gut; E-selectin and chemokine receptors CCR4 and CCR10 for the skin, in both mice and humans) [51]. In humans, the α4β7 inhibitor vedolizumab has been used to block T cell trafficking to the gut, with up to 95% efficacy in treating steroid-refractory colitis in a small cohort of cancer patients (28 patients with melanoma, RCC, prostate, or urothelial cancer) receiving checkpoint inhibitors (either anti-CTLA-4 or anti-PD-1/L1 alone or combination anti-PD-1/ anti-CTLA-4) [52]. However, this approach may be less effective for other tissues (e.g.…”

Systematic review with meta‐analysis: effectiveness of anti‐inflammatory therapy in immune checkpoint inhibitor‐induced enterocolitis

“…44 The 2018 vedolizumab Abu-Sbeih et al study, which included patients from the cohort in their most recent series, describes one patient who developed a skin rash and another with diffuse joint pain after one dose leading to discontinuation. 53 While our study focused on the most widely used agents currently used to treat checkpoint inhibitor-induced colitis, other therapies such as 5-aminosalicylic acid (5-ASA), calcineurin inhibitors and mycophenolate mofetil (MMF) have been described, albeit with relatively sparse data. 13,[19][20][21][22]49,50 The success of 5-ASA therapy has been variable, 49,50 but given these agents have a lower cost and toxicity profile, prospective data on the value of 5-ASA intervention would be welcome.…”

Clinical characteristics of colitis induced by taxane-based chemotherapy

“…In recent years, colitis induced by cancer therapies, especially immune checkpoint inhibitors, has drawn the interest of gastroenterologists worldwide [35][36][37][38][39]. Some even argue that immune checkpoint-inhibitor-induced colitis should be recognized as a new inflammatory bowel disease entity [35,[40][41][42].…”