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Clinical outcomes of patients with corticosteroid refractory immune checkpoint inhibitor induced enterocolitis treated with infliximab
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Title: | Clinical outcomes of patients with corticosteroid refractory immune checkpoint inhibitor induced enterocolitis treated with infliximab |
Authors: | Alexander, J Ibraheim, H Sheth, B Little, J Khan, MS Richards, C Hunter, N Chauhan, D Ratnakumaran, R McHugh, K Pinato, DJ Nathan, P Choy, J Cursz, SM Furness, A Turajlic, S Pickering, L Larkin, J Teare, J Papa, S Speight, A Powell, N |
Item Type: | Journal Article |
Abstract: | Introduction Immune Checkpoint Inhibitors (CPI) have changed the treatment landscape for many cancers, but also cause severe inflammatory side effects including enterocolitis. CPI-induced enterocolitis is treated empirically with corticosteroids, and infliximab (IFX) is used in corticosteroid-refractory cases. However, robust outcome data for these patients are scarce. Methods We conducted a multi-centre (six cancer centres), cohort study of outcomes in patients treated with IFX for corticosteroid-refractory CPI-induced enterocolitis between 2007 and 2020. The primary outcome was corticosteroid-free clinical remission (CFCR) with CTCAE grade 0 for diarrhoea at 12 weeks after IFX initiation. We also assessed cancer outcomes at one year using RECIST criteria. Results 127 patients (73 male; median age 59 years) were treated with IFX for corticosteroid-refractory CPI-induced enterocolitis. Ninety-six (75.6%) patients had diarrhoea CTCAE grade >2 and 115 (90.6%) required hospitalisation for colitis. CFCR was 41.2% at 12 weeks and 50.9% at 26 weeks. In multivariable logistical regression, IFX-resistant enterocolitis was associated with rectal bleeding (OR 0.19; 95% CI 0.04-0.80; p=0.03) and absence of colonic crypt abscesses (OR 2.16; 95% CI 1.13-8.05; p=0.03). Cancer non-progression was significantly more common in patients with IFX-resistant enterocolitis (64.4%) as compared to patients with IFX-responsive enterocolitis (37.5%; p=0.013). Conclusion This is the largest study to date reporting outcomes of IFX therapy in patients with corticosteroid-refractory CPI-induced enterocolitis. Utilizing pre-defined robust endpoints, we have demonstrated that fewer than half of patients achieved CFCR. Our data also indicate that cancer outcomes may be better in patients developing prolonged and severe inflammatory side effects of CPI-therapy. |
Issue Date: | 7-Jul-2021 |
Date of Acceptance: | 29-Apr-2021 |
URI: | http://hdl.handle.net/10044/1/89660 |
DOI: | 10.1136/jitc-2021-002742 |
ISSN: | 2051-1426 |
Publisher: | BioMed Central |
Start Page: | 1 |
End Page: | 9 |
Journal / Book Title: | Journal for ImmunoTherapy of Cancer |
Volume: | 9 |
Issue: | 7 |
Copyright Statement: | © Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY. Published by BMJ. https://creativecommons.org/licenses/by/4.0/ This is an open access article distributed in accordance with the Creative Commons Attribution 4.0 Unported (CC BY 4.0) license, which permits others to copy, redistribute, remix, transform and build upon this work for any purpose, provided the original work is properly cited, a link to the licence is given, and indication of whether changes were made. See https://creativecommons.org/licenses/by/4.0/. |
Sponsor/Funder: | Freed Foundation |
Funder's Grant Number: | Freed Foundation |
Keywords: | autoimmunity immunotherapy inflammation |
Publication Status: | Published |
Online Publication Date: | 2021-07-07 |
Appears in Collections: | Department of Metabolism, Digestion and Reproduction Department of Surgery and Cancer Faculty of Medicine |
This item is licensed under a Creative Commons License