P1193 - Prognostic Value of IBD-Associated Genetic Variants in Patients With Immune Checkpoint Inhibitor (ICI) Enteritis/Colitis

Award: Presidential Poster Award

Award: Presidential Poster Award

Lawrence Kogan, MD¹, Dhanya Raj, MD², Anita Giobbie-Hurder, MSc³, Shilpa Grover, MD, MPH^2
1Brown University, Providence, RI; ²Brigham & Women's Hospital, Boston, MA; ³Dana-Farber Cancer Institute, Boston, MA

Introduction: Colitis is a frequent toxicity of immune checkpoint inhibitor (ICI) therapy and mimics inflammatory bowel disease (IBD). Specific serological markers and genetic polymorphisms have been associated with IBD. However, the utility of these IBD-associated genetic and serologic biomarkers in predicting the disease course of patients with ICI colitis is unclear.

Methods: Cancer patients with histologically confirmed ICI enteritis/colitis and no history of IBD underwent commercial IBD panel testing. The panel included 4 genetic markers (ATG16L1, NXK2–3, ECM1, STAT3), 7 serological markers (anti-A4-Fla2, anti-A4-FlaX, anti-CBir1, anti-OmpC, ASCA-IgA, ASCA-IgG, pANCA), and 5 inflammatory markers (vascular endothelial growth factor [VEGF], intracellular adhesion molecule 1[ICAM-1], vascular cell adhesion molecule 1 [VCAM-1], C-reactive protein, serum amyloid A [SAA]). Clinical testing on serum samples was performed by Prometheus Laboratories (San Diego, CA). Clinical data were abstracted from medical records.

Results: Of the 16 patients, 11 patients had severe (≥ grade 3) colitis. Twelve patients received a maximal steroid dose of 1 mg/kg and 4 received 2 mg/kg, 7 patients required infliximab for management of ICI colitis. Serum SAA levels but not CRP were significantly higher in patients with severe ICI enteritis/colitis as compared with mild/moderate disease (SAA mean 60.5 vs 15.2). Expression of the ATG16L1 T300A single nuclear polymorphism (SNP) was significantly associated with the need for higher doses of steroids, with homozygotes more likely to require 2mg/kg as compared with heterozygotes (p=0.008, Table 1). The absolute level of ASCA IgA and ASCA IgG were also significantly lower in patients who required high dose steroids or biologics (p=0.01 for both).

Discussion: In this pilot study, a mutation in ATG16L1, a SNP involved in the autophagic response to invading pathogens, and a risk factor for Crohn’s disease, was more likely to be homozygous in patients with ICI induced enteritis/colitis who required higher doses of steroids. If validated, this may identify patients who could benefit from early and aggressive treatment for ICI enteritis/colitis and has the potential to improve outcomes. Serologic markers associated with IBD were not associated with the need for aggressive treatment.



Disclosures:


Lawrence Kogan, MD¹, Dhanya Raj, MD², Anita Giobbie-Hurder, MSc³, Shilpa Grover, MD, MPH². P1193 - Prognostic Value of IBD-Associated Genetic Variants in Patients With Immune Checkpoint Inhibitor (ICI) Enteritis/Colitis, ACG 2021 Annual Scientific Meeting Abstracts. Las Vegas, Nevada: American College of Gastroenterology.