Concurrent immune checkpoint inhibition and selective immunosuppressive therapy in patients with immune-related enterocolitis.

Autor:	Badran YR; Division of Gastroenterology, Department of Internal Medicine, Massachusetts General Hospital, Boston, Massachusetts, USA.; Harvard Medical School, Boston, MA, USA., Zou F; Department of Gastroenterology, Hepatology and Nutrition, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.; Department of Oncology, The Second Xiangya Hospital of Central South University, Changsha, Hunan, People's Republic of China., Durbin SM; Harvard Medical School, Boston, MA, USA.; Department of Internal Medicine, Massachusetts General Hospital, Boston, Massachusetts, USA., Dutra BE; Department of Internal Medicine, The University of Texas Health Science Center at Houston, Houston, Texas, USA., Abu-Sbeih H; Department of Internal Medicine, University of Missouri Kansas City, Kansas City, Missouri, USA., Thomas AS; Department of Gastroenterology, Hepatology and Nutrition, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA., Altan M; Department of Thoracic, Head & Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA., Thompson JA; Department of Medicine, Division of Oncology, Fred Hutchinson Cancer Research Center, Seattle Cancer Care Alliance, University of Washington, Seattle, Washington, USA., Qiao W; Department of Biostatistics, University of Texas MD Anderson Cancer Center, Houston, Texas, USA., Leet DE; Harvard Medical School, Boston, MA, USA.; Department of Internal Medicine, University of California San Francisco, San Francisco, California, USA., Lai PY; Biostatistics Center, Massachusetts General Hospital, Boston, MA, USA., Horick NK; Biostatistics Center, Massachusetts General Hospital, Boston, MA, USA., Postow MA; Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York, USA.; Department of Medicine, Weill Cornell Medical Center, New York, New York, USA., Faleck DM; Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York, USA mldougan@partners.org YWang59@mdanderson.org faleckd@mskcc.org.; Department of Medicine, Weill Cornell Medical Center, New York, New York, USA., Wang Y; Department of Gastroenterology, Hepatology and Nutrition, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA mldougan@partners.org YWang59@mdanderson.org faleckd@mskcc.org., Dougan M; Division of Gastroenterology, Department of Internal Medicine, Massachusetts General Hospital, Boston, Massachusetts, USA mldougan@partners.org YWang59@mdanderson.org faleckd@mskcc.org.; Harvard Medical School, Boston, MA, USA.
Jazyk:	angličtina
Zdroj:	Journal for immunotherapy of cancer [J Immunother Cancer] 2023 Jun; Vol. 11 (6).
DOI:	10.1136/jitc-2023-007195
Abstrakt:	Purpose: Immune checkpoint inhibitor (ICI) therapy is often suspended because of immune-related enterocolitis (irEC). We examined the effect of resumption of ICIs with or without concurrent selective immunosuppressive therapy (SIT) on rates of symptom recurrence and survival outcomes. Methods: This retrospective, multicenter study examined patients who were treated with ICI and developed irEC requiring SIT (infliximab or vedolizumab) for initial symptom control or to facilitate steroid tapering between May 2015 and June 2020. After symptom resolution, patients were restarted either on ICI alone or on concurrent ICI and SIT at the discretion of the treating physicians. The associations between irEC recurrence and treatment group were assessed via univariate analyses and multivariate logistic regression. Cox proportional hazards model was used for survival analysis. Results: Of the 138 included patients who required SIT for initial irEC symptom control, 61 (44.2%) patients resumed ICI without concurrent SIT (control group) and 77 (55.8%) patients resumed ICI therapy with concurrent SIT: 33 with infliximab and 44 with vedolizumab. After symptom resolution, patients in the control group were more commonly restarted on a different ICI regimen (65.6%) compared with those receiving SIT (31.2%) (p<0.001). The total number of ICI doses administered after irEC resolution and ICI resumption was similar in both groups (four to five doses). Recurrence of severe colitis or diarrhea after ICI resumption was seen in 34.4% of controls compared with 20.8% of patients receiving concurrent SIT. Concurrent SIT was associated with reduced risk of severe irEC recurrence after ICI resumption in a multivariate logistic regression model (OR 0.34; 95% CI 0.13 to 0.92; p=0.034). There was no difference in survival outcomes between patients in the control group and patients concurrently treated with SIT. Conclusion: After resolution of irEC symptoms, reinitiation of ICI with concurrent SIT is safe, reduces severe irEC recurrence, and has no negative impact on survival outcomes. Competing Interests: Competing interests: Unrelated to this work, YRB has consulting fees from Aditum Bio and Goodpath. MD has research funding from Novartis and Eli Lilly, has received consulting fees from Tillotts Pharma, ORIC Pharmaceuticals, Partner Therapeutics, SQZ Biotech, AzurRx, Mallinckrodt Pharmaceuticals, and Moderna, and is a member of the Scientific Advisory Board for Neoleukin Therapeutics. DF has received consulting fees from Kaleido Biosciences, AzurRx, Mallinckrodt Pharmaceuticals, and Equillium. MP has received consulting fees from BMS, Merck, Array BioPharma, Novartis, Incyte, NewLink Genetics, Aduro, Eisai, Pfizer; honoraria from BMS and Merck; institutional support from RGenix, Infinity, BMS, Merck, Array BioPharma, Novartis, and AstraZeneca. (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)
Databáze:	MEDLINE
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