Clinical Commander

Back to dossier
onc.irae-management.core.v1PRODUCTION
onc.irae-management.core.v1

Immune-related adverse events (irAE) — checkpoint inhibitor toxicity management

oncologyacuteadultgeriatric
Hard-required inputs
0 / 7

Encounter flow

12/12 authored

Canonical 12-phase frame with authored status for this dossier.

Current phase

Frame

Detailed

Identify ICI class + combination status + time-since-dose; flag prior irAE; flag known autoimmune comorbidity. Combination ipi+nivo carries 2-3x irAE severity vs monotherapy (CheckMate-067 PMID 28889792)

Inputs
2
Actions
0
Advance rule
Set
Advance when

ICI exposure profile documented (NCCN 2024)

Patient inputs (14)

Prior irAE increases recurrence risk; multi-organ pattern (Triple-M) requires aggressive workup

Cancer prognosis informs decision on permanent ICI discontinuation

PD-1 vs PD-L1 vs CTLA-4 vs combination; combination ipi+nivo carries 2-3x irAE severity (CheckMate-067)

Time-since-dose helps differentiate irAE timing; peak myocarditis 4-6 wk; colitis often after cycle 2-3; thyroiditis at any cycle

Baseline cytopenia; rules out concurrent neutropenia

AST/ALT/bilirubin/ALP for hepatitis grading (CTCAE v5)

eGFR baseline; nephritis screen; steroid dose adjustment

Pre-existing autoimmune disease (IBD, RA, SLE) baseline state and flare risk

High-sensitivity troponin is most sensitive ICI myocarditis screen; treat any elevation empirically (Mahmood JACC 2018 PMID 29567210)

Endocrinopathy screen — thyroiditis most common; hypophysitis primarily ipi; adrenal crisis screen

CK rises in myositis; combined irAE with myocarditis common (Triple-M)

Lipase elevation suggests pancreatitis irAE

ECG for AV block, ventricular ectopy — characteristic in ICI myocarditis

COP-like or NSIP-like patterns common in ICI pneumonitis

* = hard-required. Engine cannot meaningfully run until these are filled.

Severity triggers (7)

7 need judgement
  • informationallife_threateningici_myocarditis_any_troponin_elevation
    ANY troponin elevation in an ICI patient — empirically treat as myocarditis; do not wait for cardiac MRI or biopsy (Mahmood JACC 2018 PMID 29567210)
    Trigger could not be auto-evaluated — needs clinician judgement.
  • informationallife_threateningici_pneumonitis_grade_3_4_with_hypoxia
    Grade 3-4 ICI pneumonitis with SpO2 <90% on RA or O2 requirement >4 L/min
    Trigger could not be auto-evaluated — needs clinician judgement.
  • informationallife_threateningici_colitis_grade_4_with_perforation_or_megacolon
    Grade 4 ICI colitis with bowel perforation or toxic megacolon
    Trigger could not be auto-evaluated — needs clinician judgement.
  • informationallife_threateningici_hepatitis_grade_4_fulminant
    ALT >20x ULN or bilirubin >3x ULN with INR rise — fulminant ICI hepatitis
    Trigger could not be auto-evaluated — needs clinician judgement.
  • informationallife_threateningici_adrenal_crisis_from_hypophysitis
    Hypotension + hyponatremia + hyperkalemia in ICI patient — secondary adrenal insufficiency from hypophysitis; primary adrenal irAE rare
    Trigger could not be auto-evaluated — needs clinician judgement.
  • informationallife_threateningici_neurologic_with_respiratory_weakness
    Guillain-Barre or myasthenia-like syndrome with rising NIF, vital capacity drop, bulbar symptoms — impending respiratory failure
    Trigger could not be auto-evaluated — needs clinician judgement.
  • informationallife_threateningici_combined_irae_triple_m_myocarditis_myositis_myasthenia
    Combined myocarditis + myositis + myasthenia-like syndrome (Triple-M) — worse prognosis than any alone
    Trigger could not be auto-evaluated — needs clinician judgement.

Workflow calculators

Run this disease's risk and dosing calculators inline.

INITIAL_WORKUPrequiredDrives dose adjustment
Loading…

Recommended regimen

ICI colitis — steroids -> infliximab -> vedolizumab
axis: irae_colitis
Selected axis "ICI colitis — steroids -> infliximab -> vedolizumab" by default fallback (first axis)
  • prednisone
    first line
    systemic_corticosteroid
    1 mg/kg/day (max 80 mg) PO • PO • once daily then taper over 4-6 weeks
    triggers: colitis_grade_2
    NCCN 2024 / ASCO 2021 (Schneider PMID 34724392) — grade 2 colitis: hold ICI, start oral prednisone 1 mg/kg, taper over 4-6 wk
    rxcui 8640
  • budesonide
    first line
    topical_corticosteroid
    9 mg PO once daily • PO • once daily
    triggers: colitis_grade_1_2_distal_disease
    Oral budesonide (ileal release) for mild-moderate colitis or as steroid-sparing during taper
    rxcui 19831
  • methylprednisolone
    first line
    systemic_corticosteroid
    1-2 mg/kg/day IV • IV • q24h
    triggers: colitis_grade_3_4
    NCCN 2024 — grade 3-4 colitis: IV methylprednisolone 1-2 mg/kg/d; transition to oral once improving
    rxcui 6902
  • infliximab
    second line
    TNF_alpha_inhibitor
    5 mg/kg IV • IV • one dose; may repeat at 2 weeks if needed
    triggers: colitis_steroid_refractory_after_3_to_5_days
    NCCN 2024 / ESMO 2022 (Haanen PMID 36270461) — infliximab for steroid-refractory ICI colitis; rapid response typical
    rxcui 191831
  • vedolizumab
    second line
    integrin_inhibitor
    300 mg IV • IV • weeks 0, 2, 6 then q8w
    triggers: colitis_steroid_dependent_or_infliximab_refractory
    NCCN 2024 — gut-selective vedolizumab for steroid-dependent or infliximab-refractory ICI colitis (Bergqvist 2017)
    rxcui 1538097

Auto-drafted A&P note

Subjective

- Possible entry pathways: Active checkpoint inhibitor therapy (PD-1/PD-L1/CTLA-4/LAG-3) with new symptom or laboratory abnormality of any organ system — irAE until proven otherwise (NCCN 2024); Any troponin elevation in an ICI patient — STAT cardiology + STAT empiric methylprednisolone 1 g IV (Mahmood JACC 2018 PMID 29567210); Diarrhea >4 stools above baseline, or any bloody stool, in an ICI patient — suspect colitis (NCCN 2024).

Objective

- No vitals, labs, or imaging entered for this encounter.

Assessment

**Immune-related adverse events (irAE) — checkpoint inhibitor toxicity management** (onc.irae-management.core.v1).
Phenotype framing: irAE vs disease progression vs infection vs other drug toxicity vs metastasis; multi-organ "Triple-M" syndrome (myocarditis + myositis + myasthenia) — recognise early as it worsens prognosis (NCCN 2024)
Scope: Identify ICI class + combination status + time-since-dose; flag prior irAE; flag known autoimmune comorbidity. Combination ipi+nivo carries 2-3x irAE severity vs monotherapy (CheckMate-067 PMID 28889792)

No severity triggers fired against current inputs.

Plan

Regimen axis: **ICI colitis — steroids -> infliximab -> vedolizumab**.
1. prednisone 1 mg/kg/day (max 80 mg) PO PO once daily then taper over 4-6 weeks (systemic_corticosteroid, first line) — NCCN 2024 / ASCO 2021 (Schneider PMID 34724392) — grade 2 colitis: hold ICI, start oral prednisone 1 mg/kg, taper over 4-6 wk
2. budesonide 9 mg PO once daily PO once daily (topical_corticosteroid, first line) — Oral budesonide (ileal release) for mild-moderate colitis or as steroid-sparing during taper
3. methylprednisolone 1-2 mg/kg/day IV IV q24h (systemic_corticosteroid, first line) — NCCN 2024 — grade 3-4 colitis: IV methylprednisolone 1-2 mg/kg/d; transition to oral once improving
4. infliximab 5 mg/kg IV IV one dose; may repeat at 2 weeks if needed (TNF_alpha_inhibitor, second line) — NCCN 2024 / ESMO 2022 (Haanen PMID 36270461) — infliximab for steroid-refractory ICI colitis; rapid response typical
5. vedolizumab 300 mg IV IV weeks 0, 2, 6 then q8w (integrin_inhibitor, second line) — NCCN 2024 — gut-selective vedolizumab for steroid-dependent or infliximab-refractory ICI colitis (Bergqvist 2017)

AVOID / contraindication checks:
- Rule_out_c_diff_and_cmv_before_starting_steroid (infectious colitis differential)
- Infliximab_contraindicated_in_active_HF_or_severe_infection
- Pjp_prophylaxis_if_pred_above_20mg_for_4_weeks (TMP SMX 3x/wk)

Monitoring

Regimen monitoring:
- symptom grading daily during admission
- flex sig at 4 6 weeks for severe disease
- CMV PCR if no steroid response 3 5 days

Follow-up plan: Steroid taper over 4-6 wk minimum; PJP prophylaxis (TMP-SMX 3x/wk) if prednisone >20 mg for >4 wk; PPI; calcium + vitamin D + bisphosphonate for long-term steroid; endocrinopathy permanent replacement (levothyroxine, hydrocortisone, insulin); rechallenge decision per NCCN 2024 — most G3 + all G4 myocarditis/pneumonitis/encephalitis/hepatitis permanently discontinue; G2 rechallenge feasible after resolution. Multidisciplinary cancer follow-up with primary oncology team for alternative therapy if permanent d/c (NCCN 2024)
- Close-out criterion: Steroid taper + prophylaxis + replacement + rechallenge decision + oncology follow-up documented (NCCN 2024)

Monitoring phase: Daily labs during admission (LFT, creatinine, glucose, troponin per organ); weekly outpatient labs during steroid taper; echo at 6 wk if myocarditis; HRCT at 4-6 wk if pneumonitis; flex sig at 4-6 wk if colitis grade >=3; TSH + cortisol q4-6 wk for endocrinopathy surveillance (NCCN 2024)

Disposition

Disposition phase: Outpatient for grade 1-2 stable with daily symptom check; admit for grade 3-4, any suspected myocarditis, severe colitis, fulminant hepatitis, neurologic with respiratory weakness, adrenal crisis, DKA. ICU for fulminant myocarditis or encephalitis or grade 4 pneumonitis. (NCCN 2024)
- Advance when: Care setting matches grade + organ severity (NCCN 2024)

Earlier-Return Triggers

Return-precaution thresholds (watch for):
- [LIFE_THREATENING] ANY troponin elevation in an ICI patient — empirically treat as myocarditis; do not wait for cardiac MRI or biopsy (Mahmood JACC 2018 PMID 29567210)
- [LIFE_THREATENING] Grade 3-4 ICI pneumonitis with SpO2 <90% on RA or O2 requirement >4 L/min
- [LIFE_THREATENING] Grade 4 ICI colitis with bowel perforation or toxic megacolon

Citations

- NCCN Immune-Related Toxicities 2024 + ASCO 2021 irAE (Schneider JCO 2021) + ESMO 2022 immunotherapy toxicity (Haanen Ann Oncol 2022) [PMID:34724392](https://pubmed.ncbi.nlm.nih.gov/34724392/)
- Cited evidence (PMID 36270461) [PMID:36270461](https://pubmed.ncbi.nlm.nih.gov/36270461/)
- Cited evidence (PMID 29567210) [PMID:29567210](https://pubmed.ncbi.nlm.nih.gov/29567210/)
- Cited evidence (PMID 28889792) [PMID:28889792](https://pubmed.ncbi.nlm.nih.gov/28889792/)

Last reconciled with current guidelines: 2026-05-26.
References
  • NCCN Immune-Related Toxicities 2024 + ASCO 2021 irAE (Schneider JCO 2021) + ESMO 2022 immunotherapy toxicity (Haanen Ann Oncol 2022) — PMID:34724392
  • Cited evidence (PMID 36270461) — PMID:36270461
  • Cited evidence (PMID 29567210) — PMID:29567210
  • Cited evidence (PMID 28889792) — PMID:28889792