Table 1. Open in new tab Severity scale,...

	CTCAE DEFINITION¹⁶	Work-up	MANAGEMENT	Therapy
Grade 1	increase <4 stool per day or mild increase in ostomy output compared to baseline	asymptomatic	- Close monitoring	Continue ICI therapy Consider holding immunotherapy until symptoms subside	Hydration Antidiarrheal agents
Grade 2	increase of 4–6 stools per day or moderate increase in ostomy output compared to baseline	mild abdominal pain with mucus or blood in stool	Blood and stool work-up Tests for lactoferrin and calprotectin Screening laboratories^a Abdominal and pelvic Imaging (CT) GI endoscopy with biopsy	- Drug-free period until symptoms recover to G1	- Discontinue Anti CTLA-4 until symptoms recover to G1 and consider switch to anti-PD1/PD-L1 after resolution of toxicity	- Corticosteroids; if no response in 2–3 days consider increase dose or adding Infliximab
Grade 3	increase of ≥7 stools per day or severe increase in ostomy output compared to baseline	severe abdominal pain with/without peritoneal signs	Consider hospitalization As Grade 2 and consider repeating endoscopy for not responding patients	- Corticosteroids; if no response add infliximab; if no response consider vedolizumab
Grade 4	life threatening consequences	- Permanently discontinue treatment	- As Grade 3, but consider starting Infliximab earlier

CTCAE DEFINITION¹⁶

Work-up

MANAGEMENT

Therapy

Severity of diarrhea

Symptoms of colitis

Anti PD-1/PD-L1

Anti CTLA-4 or combined therapy

Grade 1

increase <4 stool per day or mild increase in ostomy output compared to baseline

asymptomatic

- Close monitoring

Grade 2

increase of 4–6 stools per day or moderate increase in ostomy output compared to baseline

mild abdominal pain with mucus or blood in stool

- Drug-free period until symptoms recover to G1

- Discontinue Anti CTLA-4 until symptoms recover to G1 and consider switch to anti-PD1/PD-L1 after resolution of toxicity

- Corticosteroids; if no response in 2–3 days consider increase dose or adding Infliximab

Grade 3

increase of ≥7 stools per day or severe increase in ostomy output compared to baseline

severe abdominal pain with/without peritoneal signs

- Corticosteroids; if no response add infliximab; if no response consider vedolizumab

Grade 4

life threatening consequences

- Permanently discontinue treatment

- As Grade 3, but consider starting Infliximab earlier

	CTCAE DEFINITION¹⁶	Work-up	MANAGEMENT	Therapy
Grade 1	increase <4 stool per day or mild increase in ostomy output compared to baseline	asymptomatic	- Close monitoring	Continue ICI therapy Consider holding immunotherapy until symptoms subside	Hydration Antidiarrheal agents
Grade 2	increase of 4–6 stools per day or moderate increase in ostomy output compared to baseline	mild abdominal pain with mucus or blood in stool	Blood and stool work-up Tests for lactoferrin and calprotectin Screening laboratories^a Abdominal and pelvic Imaging (CT) GI endoscopy with biopsy	- Drug-free period until symptoms recover to G1	- Discontinue Anti CTLA-4 until symptoms recover to G1 and consider switch to anti-PD1/PD-L1 after resolution of toxicity	- Corticosteroids; if no response in 2–3 days consider increase dose or adding Infliximab
Grade 3	increase of ≥7 stools per day or severe increase in ostomy output compared to baseline	severe abdominal pain with/without peritoneal signs	Consider hospitalization As Grade 2 and consider repeating endoscopy for not responding patients	- Corticosteroids; if no response add infliximab; if no response consider vedolizumab
Grade 4	life threatening consequences	- Permanently discontinue treatment	- As Grade 3, but consider starting Infliximab earlier

Table 1.

Severity scale, management, and workup of lower GI IRAEs (^20,23)

	CTCAE DEFINITION¹⁶		Work-up	MANAGEMENT		Therapy
	Severity of diarrhea	Symptoms of colitis	Work-up	Anti PD-1/PD-L1	Anti CTLA-4 or combined therapy	Therapy
Grade 1	increase <4 stool per day or mild increase in ostomy output compared to baseline	asymptomatic	- Close monitoring	Continue ICI therapy Consider holding immunotherapy until symptoms subside		Hydration Antidiarrheal agents
Grade 2	increase of 4–6 stools per day or moderate increase in ostomy output compared to baseline	mild abdominal pain with mucus or blood in stool	Blood and stool work-up Tests for lactoferrin and calprotectin Screening laboratories^a Abdominal and pelvic Imaging (CT) GI endoscopy with biopsy	- Drug-free period until symptoms recover to G1	- Discontinue Anti CTLA-4 until symptoms recover to G1 and consider switch to anti-PD1/PD-L1 after resolution of toxicity	- Corticosteroids; if no response in 2–3 days consider increase dose or adding Infliximab
Grade 3	increase of ≥7 stools per day or severe increase in ostomy output compared to baseline	severe abdominal pain with/without peritoneal signs	Consider hospitalization As Grade 2 and consider repeating endoscopy for not responding patients	- Drug-free period until symptoms recover to G1		- Corticosteroids; if no response add infliximab; if no response consider vedolizumab
Grade 4	life threatening consequences			- Permanently discontinue treatment		- As Grade 3, but consider starting Infliximab earlier

	CTCAE DEFINITION¹⁶		Work-up	MANAGEMENT		Therapy
	Severity of diarrhea	Symptoms of colitis	Work-up	Anti PD-1/PD-L1	Anti CTLA-4 or combined therapy	Therapy
Grade 1	increase <4 stool per day or mild increase in ostomy output compared to baseline	asymptomatic	- Close monitoring	Continue ICI therapy Consider holding immunotherapy until symptoms subside		Hydration Antidiarrheal agents
Grade 2	increase of 4–6 stools per day or moderate increase in ostomy output compared to baseline	mild abdominal pain with mucus or blood in stool	Blood and stool work-up Tests for lactoferrin and calprotectin Screening laboratories^a Abdominal and pelvic Imaging (CT) GI endoscopy with biopsy	- Drug-free period until symptoms recover to G1	- Discontinue Anti CTLA-4 until symptoms recover to G1 and consider switch to anti-PD1/PD-L1 after resolution of toxicity	- Corticosteroids; if no response in 2–3 days consider increase dose or adding Infliximab
Grade 3	increase of ≥7 stools per day or severe increase in ostomy output compared to baseline	severe abdominal pain with/without peritoneal signs	Consider hospitalization As Grade 2 and consider repeating endoscopy for not responding patients	- Drug-free period until symptoms recover to G1		- Corticosteroids; if no response add infliximab; if no response consider vedolizumab
Grade 4	life threatening consequences			- Permanently discontinue treatment		- As Grade 3, but consider starting Infliximab earlier

CTCAE: common terminology criteria for adverse events.

HIV, hepatitis A and B, and blood quantiferon for tuberculosis, to prepare patients to start Infliximab.