Immune toxicity
Description
- Autoimmune-like inflammation from removing physiological brakes on T cells
- Any organ, any time - including months after the last dose
- The differential for any new symptom in a patient on a checkpoint inhibitor is an irAE until proven otherwise
Agents
| Target | Drugs |
|---|---|
| CTLA-4 | Ipilimumab, tremelimumab |
| PD-1 | Nivolumab, pembrolizumab, cemiplimab, dostarlimab |
| PD-L1 | Atezolizumab, durvalumab, avelumab |
| LAG-3 | Relatlimab |
Toxicity burden
- Combination ipi/nivo > ipilimumab alone > anti-PD-1 alone
- Combination -> more hepatic and pulmonary toxicity, and more concurrent multi-organ toxicity
Class-specific pattern - high yield
| Anti-CTLA-4 | Anti-PD-1/PD-L1 | |
|---|---|---|
| Signature | Colitis, hypophysitis | Thyroiditis, pneumonitis |
| Dose-related | Yes | No |
| Onset | Earlier, weeks 6-12 | Variable |
Distinguish from other immune toxicity
- CAR-T / bispecifics -> cytokine release syndrome + ICANS, not irAEs - different mechanism, tocilizumab first
- Chemo/TKI toxicity is dose-dependent and predictable; irAEs are not
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