Immunotherapy toxicities- Diarrhea and colitis

 GI toxicity

Timing: 1 month after starting CTLA4 , 2-4 months after PDL1 and PD1. Can happen within 2 months of discontinuation

Symptoms: diarrhea, abd pain, fever, bleeding per rectum less common

Testing:

1. Rule out infectino: C dif, Gi multiplex stool, lactoferrin, calprotectin

2. Sensitivity of lactoferrin ( 90% on bx , 70% on endoscopy)

3. calprotectin-- higher levels predict higher risk of ulcers and serious findings on endoscopy

4. Do both lactoferrin and calprotectin if available. If lactoferrin is elevated at baseline, ( quick turnaround, if positive get endoscopy). Repeat calprotectin 2 months into rx. Lactoferrin not sensitive on treatment.

What are the high risk features associated with prolonged hospitalization and steroid refractoriness?

> 1 cm wide, Deep ulcers > 2mm, or > 3 in number--> start infliximab along with steroids

At baseline do a colonoscopy if lactoferrin elevated. If inflammation restricted to left colon ( better prognosis) alone, then ok to consider flex sig in the future i. e at 2 months

MD Anderson protocol

ESMO IO guidelines

What if there is no immune mediated colitis on endoscopy? Pt presents with diarrhea without colitis symptoms ( abd pain, rectal bleeding, blood or mucus in stool)

- GI  consult/ ID consult ( if positive CMV etc or immune compromised)

-bland food

- hydration 2-3 liters per day

- cholestyramine or colesevalem or mesalamine

What is the risk of recurrent colitis on rechallenge?

Recurrent rate of colitis is 35%