C0322 - Risk Factors Associated With Upper Gastrointestinal Bleeding in Cancer Patients Exposed to Immune Checkpoint Inhibitors

Monday, October 24, 2022

3:00 PM – 5:00 PM ET

Location: Crown Ballroom

Has Audio

Presenting Author(s)

Sadaf Afraz, DO

Cleveland Clinic Florida
Weston, Florida

Mamoon Ur Rashid, MD, Mohammad Alomari, MD, Sadaf Afraz, DO, Shruti Shettigar, MD, Kelsey Mowery, MD, Fernando Castro-Pavia, MD
Cleveland Clinic Florida, Weston, FL

Introduction: Immune checkpoint inhibitors (ICIs) have emerged as effective treatment options for many advanced malignancies. These agents have been associated with several immune related adverse events (irAEs) that may lead to discontinuation of therapy. Gastrointestinal (GI) side effects are amongst the most commonly reported irAEs. Currently, limited data exists on upper GI bleed (UGIB) in patients exposed to ICIs. The aim of this study was to evaluate the characteristics and risk factors associated with UGIB among cancer patients treated with ICIs.

Methods: We performed a retrospective study on all cancer patients from Cleveland Clinic health system who received treatment with ICI’s till June 2021. Only the patients with clinical and endoscopic evidence of upper GI bleed were included in the study. The study group (GI Bleed) was matched with control group (non-Bleeders) in 1:3. We compared characteristics of both groups (Bleeders and Non-Bleeders) using univariate and multivariate analysis.

Results: Of the 6820 patients that received ICIs over the study period, 401 patients developed GI bleed. 30 patients had clinical and endoscopic evidence of upper GI Bleed. The most common endoscopic findings were gastric and duodenal ulcers (63%). Compared with the non-bleeding cohort, patients who developed UGIB bleeding had lower BMI (p= 0.0203). Non-small cell lung cancer was the most frequently treated malignancy in the bleeding group. Patients in the bleeding group had higher exposure to pembrolizumab compared to the non-bleeding group (80% vs. 45.6%, p= 0.001). The incidence of ICI induced colitis and hepatotoxicity were more frequent in the bleeding group compared to the non-bleeding cohort (53.5% vs. 27.8%, p= 0.0106). The presence of cirrhosis, diabetes and chronic kidney disease were similar in both groups. On the multivariant analysis, exposure to pembrolizumab (OR=3.62, p=0.0211), aspirin (OR= 10.55, p=0.0002) and with history of ICI induced colitis and hepatotoxicity (OR=3.66 p=0.0108) were predictive factors in development of bleeding.

Discussion: This is a novel study that evaluates the risk of UGIB in cancer patients treated with ICIs. In this univariate and multivariate analysis, exposure to aspirin, pembrolizumab and overall incidence of IrAEs were associated with increased risk of bleeding. Although UGIB is a relatively rare irAE, more studies are needed for risk stratification of patients exposed to ICIs.

Variable	Non-Bleeding (n=90)	Bleeding (n=30)	p-value
Age, mean ± SD	70.6 ± 11.0	69.6 ± 11.3	0.6854
Gender (Male), n (%)	56 (62.2)	19 (63.3)	0.9133
Race (White), n (%)	76 (84.4)	23 (76.7)	0.3316
Hispanic, n (%)	1 (1.1)	2 (6.7)	0.1539
Medication Type, n (%) Pembrolizumab Other	41 (45.6) 49 (54.4)	24 (80.0) 6 (20.0)	0.0010
BMI, n (%) < 26 ≥ 26	38 (42.2) 52 (57.8)	20 (66.7) 10 (33.3)	0.0203
History of Upper GI Bleed, n (%)	7 (7.8)	0 (0.0)	0.1902
On Aspirin prior to procedure, n (%)	5 (5.6)	12 (40.0)	< 0.0001
On Plavix prior to procedure, n (%)	1 (1.1)	1 (3.3)	0.4391
On Warfarin prior to procedure, n (%)	0 (0.0)	1 (3.3)	0.2500
Chronic kidney disease, n (%)	34 (37.8)	13 (43.3)	0.5893
Diabetes, n (%)	33 (36.7)	9 (30.0)	0.5073
Cirrhosis, n (%)	4 (4.4)	1 (3.3)	1.0000
Type of cancer treated, n (%) Non-small cell lung cancer Other	25 (27.8) 65 (72.2)	15 (50.0) 15 (50.0)	0.0253
Evidence of metastasis to the GI Tract, n (%)	4 (4.4)	0 (0.0)	0.5710
ICPI induced side effect, n (%)	25 (27.8)	16 (53.3)	0.0106
Treatment with steroids, n (%)	21 (23.3)	11 (36.7)	0.1527
Treatment with Infliximab or Entyvio, n (%)	1 (1.1)	1 (3.3)	0.4391
Current alive, n (%)	29 (32.2)	8 (26.7)	0.5682
PPI, n (%) No Yes	53 (58.9) 37 (41.1)	17 (56.7) 13 (43.3)	0.8307

Table: Table 1: Baseline Clinical Characteristics Of Cancer Patients Exposed To ICIs.
Footnote: PPI (protein pump inhibitor).

Disclosures:

Mamoon Ur Rashid indicated no relevant financial relationships.

Mohammad Alomari indicated no relevant financial relationships.

Sadaf Afraz indicated no relevant financial relationships.

Shruti Shettigar indicated no relevant financial relationships.

Kelsey Mowery indicated no relevant financial relationships.

Fernando Castro-Pavia indicated no relevant financial relationships.

Mamoon Ur Rashid, MD, Mohammad Alomari, MD, Sadaf Afraz, DO, Shruti Shettigar, MD, Kelsey Mowery, MD, Fernando Castro-Pavia, MD. C0322 - Risk Factors Associated With Upper Gastrointestinal Bleeding in Cancer Patients Exposed to Immune Checkpoint Inhibitors, ACG 2022 Annual Scientific Meeting Abstracts. Charlotte, NC: American College of Gastroenterology.