Shilpa Grover1,2, Michael Dougan1,3, Kevin Tyan1,4, Anita Giobbie-Hurder5, Steven M Blum1,4,6,7, Jeffrey Ishizuka8, Taha Qazi2,9, Rawad Elias10, Kruti B Vora1, Alex B Ruan1, William Martin-Doyle1,11, Michael Manos4, Lauren Eastman4, Meredith Davis4, Maria Gargano4, Rizwan Haq1,4, Elizabeth I Buchbinder1,4,11, Ryan J Sullivan7, Patrick A Ott1,4,6,11, F Stephen Hodi1,4, Osama E Rahma1,4. 1. Harvard Medical School, Boston, Massachusetts. 2. Division of Gastroenterology, Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts. 3. Division of Gastroenterology, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts. 4. Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts. 5. Division of Biostatistics, Department of Data Sciences, Dana-Farber Cancer Institute, Boston, Massachusetts. 6. Broad Institute at MIT and Harvard, Cambridge, Massachusetts. 7. Massachusetts General Hospital Cancer Center, Boston, Massachusetts. 8. Departments of Medicine and Pathology, Yale University School of Medicine, New Haven, Connecticut. 9. Digestive Disease & Surgery Institute, Cleveland Clinic, Cleveland, Ohio. 10. Hartford HealthCare Cancer Institute, Hartford, Connecticut. 11. Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts.
Abstract
BACKGROUND: There is a lack of predictive markers informing on the risk of colitis in patients treated with immune checkpoint inhibitors (ICIs). The aim of this study was to identify potential factors associated with development of ICI colitis. METHODS: We performed a retrospective analysis of melanoma patients at Dana-Farber Cancer Institute who received PD-1, CTLA-4, or combination ICIs between May 2011 to October 2017. Clinical and laboratory characteristics associated with pathologically confirmed ICI colitis were evaluated using multivariable logistic regression analyses. External confirmation was performed on an independent cohort from Massachusetts General Hospital. RESULTS: The discovery cohort included 213 patients of whom 37 developed ICI colitis (17%). Vitamin D use was recorded in 66/213 patients (31%) before starting ICIs. In multivariable regression analysis, vitamin D use conferred significantly reduced odds of developing ICI colitis (OR 0.35, 95% CI 0.1-0.9). These results were also demonstrated in the confirmatory cohort (OR 0.46, 95% CI 0.2-0.9) of 169 patients of whom 49 developed ICI colitis (29%). Pre-treatment neutrophil-to-lymphocyte ratio (NLR) ≥5 predicted reduced odds of colitis (OR 0.34, 95% CI 0.1-0.9) only in the discovery cohort. CONCLUSIONS: This is the first study to report that among patients treated with ICIs, vitamin D intake is associated with reduced risk for ICI colitis. This finding is consistent with prior reports of prophylactic use of vitamin D in ulcerative colitis and graft-versus-host-disease. This observation should be validated prospectively in future studies.
BACKGROUND: There is a lack of predictive markers informing on the risk of colitis in patients treated with immune checkpoint inhibitors (ICIs). The aim of this study was to identify potential factors associated with development of ICI colitis. METHODS: We performed a retrospective analysis of melanomapatients at Dana-Farber Cancer Institute who received PD-1, CTLA-4, or combination ICIs between May 2011 to October 2017. Clinical and laboratory characteristics associated with pathologically confirmed ICI colitis were evaluated using multivariable logistic regression analyses. External confirmation was performed on an independent cohort from Massachusetts General Hospital. RESULTS: The discovery cohort included 213 patients of whom 37 developed ICI colitis (17%). Vitamin D use was recorded in 66/213 patients (31%) before starting ICIs. In multivariable regression analysis, vitamin D use conferred significantly reduced odds of developing ICI colitis (OR 0.35, 95% CI 0.1-0.9). These results were also demonstrated in the confirmatory cohort (OR 0.46, 95% CI 0.2-0.9) of 169 patients of whom 49 developed ICI colitis (29%). Pre-treatment neutrophil-to-lymphocyte ratio (NLR) ≥5 predicted reduced odds of colitis (OR 0.34, 95% CI 0.1-0.9) only in the discovery cohort. CONCLUSIONS: This is the first study to report that among patients treated with ICIs, vitamin D intake is associated with reduced risk for ICI colitis. This finding is consistent with prior reports of prophylactic use of vitamin D in ulcerative colitis and graft-versus-host-disease. This observation should be validated prospectively in future studies.
Authors: L von Bahr; O Blennow; J Alm; A Björklund; K-J Malmberg; D Mougiakakos; A Le Blanc; P J Oefner; M Labopin; P Ljungman; K Le Blanc Journal: Bone Marrow Transplant Date: 2015-06-01 Impact factor: 5.483
Authors: Estrella Carrillo-Cruz; José R García-Lozano; Francisco J Márquez-Malaver; Fermín M Sánchez-Guijo; Isabel Montero Cuadrado; Christelle Ferra I Coll; David Valcárcel; Oriana López-Godino; Marian Cuesta; Rocío Parody; Lucía López-Corral; Miguel Alcoceba; Teresa Caballero-Velázquez; Alfonso Rodríguez-Gil; José A Bejarano-García; Teresa Lopes Ramos; José A Pérez-Simón Journal: Clin Cancer Res Date: 2019-05-01 Impact factor: 12.531
Authors: L Marthey; C Mateus; C Mussini; M Nachury; S Nancey; F Grange; C Zallot; L Peyrin-Biroulet; J F Rahier; M Bourdier de Beauregard; L Mortier; C Coutzac; E Soularue; E Lanoy; N Kapel; D Planchard; N Chaput; C Robert; F Carbonnel Journal: J Crohns Colitis Date: 2016-01-18 Impact factor: 9.071
Authors: Kristen E Pauken; Michael Dougan; Noel R Rose; Andrew H Lichtman; Arlene H Sharpe Journal: Trends Immunol Date: 2019-04-30 Impact factor: 16.687
Authors: A M Menzies; D B Johnson; S Ramanujam; V G Atkinson; A N M Wong; J J Park; J L McQuade; A N Shoushtari; K K Tsai; Z Eroglu; O Klein; J C Hassel; J A Sosman; A Guminski; R J Sullivan; A Ribas; M S Carlino; M A Davies; S K Sandhu; G V Long Journal: Ann Oncol Date: 2017-02-01 Impact factor: 32.976
Authors: Ahmad A Tarhini; Haris Zahoor; Yan Lin; Usha Malhotra; Cindy Sander; Lisa H Butterfield; John M Kirkwood Journal: J Immunother Cancer Date: 2015-09-15 Impact factor: 13.751
Authors: Kevin Tyan; Joanna Baginska; Martha Brainard; Anita Giobbie-Hurder; Mariano Severgnini; Michael Manos; Rizwan Haq; Elizabeth I Buchbinder; Patrick A Ott; F Stephen Hodi; Osama E Rahma Journal: Cancer Immunol Immunother Date: 2021-01-22 Impact factor: 6.968
Authors: Harm Westdorp; Mark W D Sweep; Mark A J Gorris; Frank Hoentjen; Marye J Boers-Sonderen; Rachel S van der Post; Michel M van den Heuvel; Berber Piet; Annemarie Boleij; Haiko J Bloemendal; I Jolanda M de Vries Journal: Front Immunol Date: 2021-10-29 Impact factor: 7.561
Authors: Mahlatse C M Kgokolo; Katherine Anderson; Shalate C Siwele; Helen C Steel; Luyanda L I Kwofie; Mike M Sathekge; Pieter W A Meyer; Bernardo L Rapoport; Ronald Anderson Journal: Front Oncol Date: 2022-02-11 Impact factor: 6.244