Table 4 Work-up of critically ill cancer patients admitted to the ICU suspected for an IRAE

Basic evaluation

(1) When was the treatment with checkpoint inhibitor started and how many doses has the patient already received?

(2) Which is/are the leading symptom/s and when did it/they start?

(3) Which grading definition(s) according to NCI CTCAE is fulfilled?

(4) Rule out important differential diagnosis: pre-existing autoimmune condition, complication of underlying malignancy, infection

(5) What is the patient’s prognosis due to malignancy?

Initial management

(1) ICU monitoring, venous/arterial access, fluid load, vasopressors and oxygen supplementation, ultrasound, and/or CT scan as indicated

(2) Check common laboratory tests: hematology, chemistry (including renal and liver function tests), coagulation, endocrine function, microbial and viral infections, autoantibodies (e.g., ANA, AMA, SMA, LKM1, pANCA, TPOAb, TRAb, TGAb)

(3) If diagnosis of IRAEs is established, initiate steroid therapy at 1–2 mg/kg of body weight OR, if patient is already on steroids, consider increase of dose (up to 5 mg/kg or equivalent)

(4) Involve organ specialists: gastroenterology, endocrinology, and neurology, surgery (if perforation or ileus is suspected)

Advanced support

(1) If symptoms do not improve after 5–7 days, discuss additional immunosuppressive intervention (mycophenolate mofetil, tacrolimus)

(2) Consider endoscopy and colonic biopsies for patients with diarrhea/colitis, or liver biopsy in selected cases

(3) Evaluate specific recommendations for organ dysfunction:

-Hormone replacement in endocrine disorders

-Infliximab in severe colitis

(4) In responding events slowly taper steroids over 4 weeks; discuss duration of alternative immunosuppression (if needed) with organ specialist

(5) Checkpoint inhibition should be discontinued definitively after grade 3/4 IRAEs