ASCO 2021 guideline: how to recognise and manage the immune-related side effects of checkpoint inhibitors
The ASCO 2021 guideline is the consensus rulebook for checkpoint-inhibitor toxicity: grade the problem, hold or stop the drug, give steroids early, escalate to other immunosuppressants if they fail, and involve specialists.
This update of the 2018 ASCO guideline, developed with the National Comprehensive Cancer Network, provides organ-by-organ recommendations for immune-related adverse events (irAEs) of PD-1, PD-L1 and CTLA-4 inhibitors, based on systematic review and expert consensus. The general framework is graded: grade 1 events are usually managed with monitoring while continuing therapy (except some neurological, haematological and cardiac events); grade 2 events lead to holding the inhibitor and considering corticosteroids (prednisone 0.5-1 mg/kg/day); grade 3 events require holding therapy and high-dose corticosteroids (1-2 mg/kg/day) tapered over at least four to six weeks, with infliximab or other agents if no improvement in 48-72 hours; grade 4 events generally mandate permanent discontinuation, except endocrinopathies controlled by hormone replacement. Specific sections cover skin, gastrointestinal, hepatic, endocrine, pulmonary, rheumatological, renal, neurological, haematological, cardiovascular and ocular toxicities, and a companion ASCO guideline addresses CAR-T toxicities. The Society for Immunotherapy of Cancer published a parallel consensus in 2021.
- Grade-based algorithm: grade 1 monitor and continue (with exceptions); grade 2 hold and consider steroids; grade 3 hold and give 1-2 mg/kg prednisone-equivalent; grade 4 permanently discontinue except endocrinopathies.
- Steroid tapers should last at least 4-6 weeks; failure to improve within 48-72 hours should prompt infliximab (colitis, arthritis), mycophenolate (hepatitis) or other second-line immunosuppression.
- Myocarditis is rare but has high mortality and warrants high-dose steroids and early cardiology involvement; troponin monitoring is discussed.
- Hormone replacement, not steroids, is the treatment for most endocrinopathies, which are often permanent.
- Rechallenge after grade 2-3 irAEs can be considered case by case once resolved to grade 1 or less; short steroid courses do not clearly reduce efficacy.
Checkpoint inhibitors are now given to hundreds of thousands of patients a year, many in community clinics and emergency departments, so a common, explicit playbook for their autoimmune side effects saves lives. The guideline standardised when to stop, when to give steroids and when to escalate, and made multidisciplinary toxicity teams routine. It does not remove the judgement needed for rare events or for patients whose cancer is responding.
- Most recommendations rest on expert consensus and case series rather than randomised trials.
- Steroid-sparing strategies and biomarkers for irAEs remain largely unstudied.
- Guidance on rechallenge and on combination or adjuvant settings is limited.
- Rapidly evolving; later ASCO and SITC updates modify specific sections (for example, myocarditis and CAR-T toxicity).