Kadmon cGVHD Disease Education

Inflammation and Fibrosis

WHAT ROLES DO THE INFLAMMATORY AND FIBROTIC PROCESSES PLAY IN cGVHD?

Chronic graft-versus-host disease is characterized by a combination of tissue inflammation and fibrosis, which manifest across multiple organ systems.1-4

The relationship between these 2 processes in cGVHD is complex and not fully understood.3 Fibrosis may be viewed as a natural consequence of inflammation, as an independent process or as interrelated with inflammation in some ways but not completely dependent on it.5

Because of chronic inflammatory changes, cGVHD can present with collagen-producing fibroblasts,2 resulting in fibrotic lesions.2,4

Fibrotic lesions can develop across multiple organs4

cGVHD fibrotic lesions can develop on the skin, mouth, joints, eyes, GI tract, esophagus, liver and lungs
Skin
cGVHD fibrotic lesions can develop on the skin, mouth, joints, eyes, GI tract, esophagus, liver and lungs
Mouth
cGVHD fibrotic lesions can develop on the skin, mouth, joints, eyes, GI tract, esophagus, liver and lungs
Joints
cGVHD fibrotic lesions can develop on the skin, mouth, joints, eyes, GI tract, esophagus, liver and lungs
Eyes
cGVHD fibrotic lesions can develop on the skin, mouth, joints, eyes, GI tract, esophagus, liver and lungs
GI Tract
cGVHD fibrotic lesions can develop on the skin, mouth, joints, eyes, GI tract, esophagus, liver and lungs
Esophagus
cGVHD fibrotic lesions can develop on the skin, mouth, joints, eyes, GI tract, esophagus, liver and lungs
Liver
cGVHD fibrotic lesions can develop on the skin, mouth, joints, eyes, GI tract, esophagus, liver and lungs
Lungs

Fibrosis is a major contributor to life-threatening complications and significant morbidity.6

Patients develop multiorgan manifestations, including skin, mouth, joint/fascia, eye, upper and lower GI tract, esophagus, liver, genitourinary and/or lung manifestations.4,7,8

Skin manifestations are the most common, occurring in

Fibrotic skin lesions affect 80% of patients with cGVHD

Approximately half of patients have lung involvement,

About half of patients with cGVHD have lung fibrosis

which can manifest as bronchiolitis obliterans, a fibrotic manifestation that can be especially difficult to treat.7,8


Although the inflammation associated with cGVHD can be addressed, there is limited evidence regarding the impact of current treatments on fibrosis.10-15

cGVHD, chronic graft-versus-host disease; GI, gastrointestinal.

References: 1. Fall-Dickson JM, Pavletic SZ, Mays JW, Schubert MM. Oral complications of chronic graft-versus-host disease. J Natl Cancer Inst Monogr. 2019;2019(53). doi:10.1093/jncimonographs/lgz007 2. MacDonald KPA, Hill GR, Blazar BR. Chronic graft-versus-host disease: biological insights from preclinical and clinical studies. Blood. 2017;129(1):13-21. doi:10.1182/blood-2016-06-686618 3. Kitko CL, White ES, Baird K. Fibrotic and sclerotic manifestations of chronic graft-versus-host disease. Biol Blood Marrow Transplant. 2012;18(1 suppl):S46-S52. doi:10.1016/j.bbmt.2011.10.021 4. Fiuza-Luces C, Simpson RJ, Ram√≠rez M, Lucia A, Berger NA. Physical function and quality of life in patients with chronic GvHD: a summary of preclinical and clinical studies and a call for exercise intervention trials in patients. Bone Marrow Transplant. 2016;51(1):13-26. doi:10.1038/bmt.2015.195 5. Cooke KR, Luznik L, Sarantopoulos S, et al. The biology of chronic graft-versus-host disease: a task force report from the National Institutes of Health consensus development project on criteria for clinical trials in chronic graft-versus-host disease. Biol Blood Marrow Transplant. 2017;23(2):211-234. doi:10.1016/j.bbmt.2016.09.023 6. Henden AS, Hill GR. Cytokines in graft-versus-host disease. J Immunol. 2015;194(10):4604-4612. doi:10.4049/jimmunol.1500117 7. Jacobsohn DA, Kurland BF, Pidala J, et al. Correlation between NIH composite skin score, patient-reported skin score, and outcome: results from the Chronic GVHD Consortium. Blood. 2012;120(13):2545-2552. doi:10.1182/blood-2012-04-424135 8. Inamoto Y, Martin PJ, Chai X, et al; on behalf of the Chronic GVHD Consortium. The clinical benefit of response in chronic graft-versus-host disease. Biol Blood Marrow Transplant. 2012;18(10):1517-1524. doi:10.1016/j.bbmt.2012.05.016 9. Chronic graft-vs-host disease of skin and connective tissues. BMTinfonet. Accessed April 13, 2020. https://www.bmtinfonet.org/video/chronic-graft-vs-host-disease-skin-and-connective-tissues 10. Cutler CS, Koreth J, Ritz J. Mechanistic approaches for the prevention and treatment of chronic GVHD. Blood. 2017;129(1):22-29. doi:10.1182/blood-2016-08-686659 11. Jakafi. Package insert. Inctye Corporation; 2019. 12. Modi B, Hernandez-Henderson M, Yang D, et al. Ruxolitinib as salvage therapy for chronic graft-versus-host-disease. Biol Blood Marrow Transplant. 2019;25(2):265-269. doi:10.1016/j.bbmt.2018.09.003 13. Imbruvica. Package insert. Pharmacyclics LLC; 2019. 14. Hill L, Alousi A, Kebriaei P, Mehta R, Rezvani K, Shpall E. New and emerging therapies for acute and chronic graft versus host disease. Ther Adv Hematol. 2018;9(1):21-46. doi:10.1177/2040620717741860 15. Koreth J, Kim HT, Jones KT, et al. Efficacy, durability, and response predictors of low-dose interleukin-2 therapy for chronic graft-versus-host disease. Blood. 2016;128(1):130-137. doi:10.1182/blood-2016-02-702852