D0374 - Identification and Characterization of a Single-Center Cohort of Patients With Refractory or Relapsing Immune Checkpoint Inhibitor-Induced Colitis

Tuesday, October 25, 2022

10:00 AM – 12:00 PM ET

Location: Crown Ballroom

Presenting Author(s)

Thomas Fredrick, MD

Mayo Clinic Rochester
Rochester, MN

Thomas Fredrick, MD¹, Manuel B. Braga Neto, MD², Laura Raffals, MD, MS¹
¹Mayo Clinic Rochester, Rochester, MN; ²Mayo Clinic, Rochester, MN

Introduction: Immune checkpoint inhibitors (ICIs) fight cancer by turning the immune system against malignant cells, which predisposes patients to autoimmune toxicities. ICI-induced colitis is one of the most frequent toxicities encountered.

We sought to characterize and describe the disease and treatment course of those individuals who suffer prolonged courses of ICI-induced colitis to identify risk factors for refractory colitis.

Methods: Retrospective chart review was performed across s multi-site health system using a unified data platform. Cases were identified for medication administrations of FDA-approved immune checkpoint inhibitors prior to December 1^st 2021.

Charts were abstracted to determine the duration of ICI therapy, symptoms, clinical evaluation, and treatment course.

Cases were subdivided into four groups: those with a single episode of colitis responsive to colitis-directed treatment after maximum of 60 days without relapse or recurrence, cases with recurrent or worsening symptoms despite treatment, cases with a second episode despite initial resolution, and cases who never managed to achieve symptom resolution at time of last follow up.

Results: We identified 148 cases of ICI-colitis with median follow up of 1.08 (IQR 0.46-1.99) years detailed in table 1.

There were no significant differences between gender breakdown, smoking status, or history of prior chemotherapy across the subgroups. Patients had an average of 0.723 (SD 0.879) additional ICI-induced toxicities.

In individuals with a single episode of colitis, median symptom duration was 59 (IQR 24-102) days vs 137 days (p< 0.001) in refractory colitis. Cases of refractory colitis were more often treated with systemic steroid treatment (96.2%, p=0.029) and biologics (34%, p< 0.001).

19 cases experienced a second episode of colitis, despite 1 on biologic therapy and 7 on corticosteroids during ICI therapy. 47.4% of cases were hospitalized and 2 (10.5%) experiencing mortality during their second flare.

15 cases never experienced symptom control. 80% of these cases were hospitalized, and 21.4% experienced mortality from colitis despite ICI therapy being held in all instances.

Discussion: We present a large case series of patients with ICI-colitis and identify a subset of patients with refractory or relapsing symptoms. Predictive factors for these patients remain to be determined, and management relies on a combination of enteral and systemic steroids and occasionally biologic therapy.

	Single Episode of Colitis, Treated N=61	Single Episode of Colitis, Refractory Symptoms N=53	Second Episode of Colitis N=19	Single Episode of Colitis, persistent symptoms N=15	All Cases n=148
Female	28 (45.9%)	30 (56.6%)	6 (31.6%)	9 (60.0%)	73 (49.3%)
Age at first ICI median, IQR, years (median, IQR)	66.6 (57.4, 72.5)	67.9 (58.4, 71.7)	66.1 (56.8, 71.3)	70.3 (68.3, 75.7)	67.4 (57.6, 72.4)
Deceased	25 (41.0%)	15 (28.3%)	7 (36.8%)	13 (86.7%)**	60 (40.5%)
Median Follow Up After Symptom Onset, years (median, IQR)	1.04 (0.46-1.86)	1.44 (0.66-2.04)	1.93 (0.75-2.69)	0.22 (0.12-0.45)	1.08 (0.46-1.99)
Malignancy
Melanoma	27 (44.3%)	25 (47.2%)	9 (47.4%)	3 (20.0%)	64 (43.2%)
Lung Cancer-NSCLC	12 (19.7%)	13 (24.5%)	3 (15.8%)	3 (20.0%)	31 (20.9%)
Renal cell carcinoma	5 (8.2%)	4 (7.5%)	2 (13.3%)	2 (13.3%)	16 (10.8%)
Other	17 (28%)	11 (21%)	3 (16%)	7 (47%)	37 (25%)
Causative Immune Checkpoint inhibitor
Pembrolizumab	27 (44.3%)	21 (39.6%)	8 (42.1%)	7 (46.7%)	63 (42.6%)
Nivolumab	5 (8.2%)	11 (20.8%)	5 (26.3%)	0 (0.0%)	21 (14.2%)
Ipilimumab + Nivolumab	24 (39.3%)	14 (26.4%)	3 (15.8%)	6 (40.0%)	47 (31.8%)
Other	5 (8.2%)	7 (13.2%)	3 (15.8%)	2 (13.3%)	17(11.5 %)

ICI doses prior to colitis, n (median, IQR)	6 (2, 11)	6 (3, 10.250)	6 (2.500, 11)	6 (3.500, 8)	6 (3, 10.500)
Additional ICI toxicities, n (mean, SD)	0.62 (0.82)	0.77 (0.89)	0.79 (0.92)	0.87 (1.06)	0.72 (0.88)
Time from first ICI to colitis, days (median, IQR)	85 (40, 211)	127 (61, 243)	84 (43, 420)	92 (42, 125.5)		93.5 (42, 244.3)
Duration of symptoms, days (median, IQR)	59 (24, 102)	137 (74, 225) ***	65 (24.5, 102.5)	80 (43, 163)		80.500 (30.8, 146.5)
CTCAE grade
1	7 (11.5%)	6 (11.3%)	2 (10.5%)	1 (6.7%)		16 (10.8%)
2	21 (34.4%)	20 (37.7%)	7 (36.8%)	2 (13.3%)		50 (33.8%)
3	22 (36.1%)	17 (32.1%)	9 (47.4%)	6 (40.0%)		54 (36.5%)
4	11 (18.0%)	10 (18.9%)	1 (5.3%)	4 (26.7%)		26 (17.6%)
5	0 (0.0%)	0 (0.0%)	0 (0.0%)	2 (13.3%)		2 (1.4%)
Hospitalized for event	30 (49.2%)	26 (49.1%)	9 (47.4%)	12 (80.0%) *		77 (52.0%)
Mortality from Event	0 (0.0%)	0 (0.0%)	0 (0.0%)	3 (21.4%) ***		3 (2.0%)
ICI therapy held due to colitis	54 (88.5%)	46 (86.8%)	18 (94.7%)	11 (73.3%)		129 (87.2%)
Switched to another ICI	10 (16.4%)	8 (15.1%)	3 (15.8%)	1 (6.7%)		22 (14.9%)
Colonoscopy obtained	13 (21.3%)	24 (45.3%) **	3 (15.8%)	4 (26.7%)		44 (29.7%)
Sigmoidoscopy obtained	15 (24.6%)	17 (32.1%)	8 (42.1%)	4 (26.7%)		44 (29.7%)
Endoscopy confirmed colitis†	25 (89.3%)	40 (97.6%)	11 (100.0%)	7 (87.5%)		83 (94.3%)
Fecal calprotectin elevated††	6 (75.0%)	16 (88.9%)	2 (66.7%)	3 (75.0%)		27 (81.8%)
Treatment with systemic steroids	51 (83.6%)	51 (96.2%)*	16 (84.2%)	15 (100.0%)		133 (89.9%)
Duration of systemic steroid treatment, days (median, IQR)	67 (60, 111)	178.5 (93.8, 277.3)	148 (60, 238)	59 (22, 96) *		100 (61.8, 218.3)
Treatment with budesonide n, %	24 (39.3%)	30 (56.6%)	11 (57.9%)	6 (40.0%)		71 (48.0%)
Duration of budesonide treatment days (median, IQR)	138 (70.5, 244.3)	165.5 (107, 317.8)	137 (119.5, 281)	131 (104.5, 157.5)		155 (97, 280)
Treatment with biologic	5 (8.2%)	18 (34.0%) ***	2 (10.5%)	2 (13.3%)		27 (18.2%)

Table: Table 1: Demographics and disease and treatment course of cases developing immune checkpoint inhibitor colitis, broken down by four different clinical disease patterns. Those with a single episode of colitis responsive to initial treatment without relapse, those with a single episode of colitis with symptoms refractory to either initial treatment or recurrent after treatment taper, those with a second episode of colitis, and those with symptoms that never resolved at the time of last follow-up.
Values listed as n, % unless otherwise specified.
* P<0.05, ** p< 0.01, *** p<0.001
† Percentage pertains to % of cases in which endoscopy was pursued
†† Percentage obtained to % of cases in which calprotectin was obtained

Disclosures:

Thomas Fredrick indicated no relevant financial relationships.

Manuel Braga Neto indicated no relevant financial relationships.

Laura Raffals: Janssen Pharmaceuticals – Advisor or Review Panel Member.

Thomas Fredrick, MD¹, Manuel B. Braga Neto, MD², Laura Raffals, MD, MS¹. D0374 - Identification and Characterization of a Single-Center Cohort of Patients With Refractory or Relapsing Immune Checkpoint Inhibitor-Induced Colitis, ACG 2022 Annual Scientific Meeting Abstracts. Charlotte, NC: American College of Gastroenterology.