# Restarting a checkpoint inhibitor after an immune-related side effect

Source: https://onco.cc/protocols/irae-rechallenge/  
OnCo record `irae-rechallenge` (Protocol). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

After an immunotherapy side effect has settled, your team may offer to restart the same treatment. About 3 in 10 people who restart have the same side effect again, and some side effects (such as heart or nerve inflammation, or very severe reactions) usually mean stopping for good. It is a shared decision that weighs the cancer benefit against the risk.

## Summary

Rechallenge is considered once the toxicity has resolved to grade 1 or less and the patient needs no more than 10 mg prednisone a day (SITC 2021). SITC: after grade 2 irAEs, rechallenge may proceed once resolved or controlled on 10 mg/day or less (LE: 3); after grade 3 to 4, the decision is risk-adjusted (LE: 3). Factors against: severe or life-threatening irAEs, prolonged or multiple immunosuppressants, long prior treatment, and complete response or prolonged benefit. ASCO 2021 (abstract): consider resuming most grade 2 toxicities when grade 1 or less; permanently discontinue after grade 4, except endocrinopathies controlled by hormone replacement. ESE 2022: a controlled endocrinopathy is no contraindication (++00).

Organ rules in SITC: colitis needs a repeat endoscopy before resuming; pneumonitis after grade 2 only after complete resolution (LE: 4); myocarditis, Guillain-Barré syndrome and grade 3 to 4 myasthenia gravis lead to permanent or seriously considered permanent discontinuation. ADQI 2026 supports cautious rechallenge after kidney injury (recurrence under 20%).

Evidence: a WHO pharmacovigilance cohort found the same irAE recurred in 28.8% of informative rechallenges, more often after colitis, hepatitis and pneumonitis and less often after adrenal events; two small SITC-cited series found 26 to 43% recurrence and 13 to 26% new irAEs.

## Fields

- Kind: Protocol
- Last checked: 2026-11-11
- Also known as: immunotherapy rechallenge; ICI rechallenge; checkpoint inhibitor retreatment after irAE; resuming immunotherapy after toxicity; re-challenge after immune-related adverse event
- Tags: protocol; irae

## Connected records

- protocols: [Blood side effects of checkpoint inhibitors: low platelets, haemolysis, neutropenia and marrow failure](https://onco.cc/protocols/irae-haematological/), [Immune-mediated hepatitis from checkpoint inhibitors, by grade](https://onco.cc/protocols/irae-hepatitis/), [Immune-related diarrhoea and colitis from checkpoint inhibitors, by grade](https://onco.cc/protocols/irae-colitis/), [Immune-related myocarditis from checkpoint inhibitors](https://onco.cc/protocols/irae-myocarditis/), [Immune-related pneumonitis from checkpoint inhibitors, by grade](https://onco.cc/protocols/irae-pneumonitis/), [Kidney inflammation (immune-related nephritis) from checkpoint inhibitors](https://onco.cc/protocols/irae-nephritis/), [Neurological side effects of checkpoint inhibitors: myasthenia gravis, Guillain-Barré syndrome, meningitis and encephalitis](https://onco.cc/protocols/irae-neurological/), [Steroid taper after immunotherapy side effects, with Pneumocystis prophylaxis and adrenal checks](https://onco.cc/protocols/irae-steroid-taper-and-pjp/)
- pairings: [Caution: PD-1 rechallenge after progression on immunotherapy (RCC)](https://onco.cc/pairings/io-rechallenge-caution-rcc/)
- technologies: [Immune checkpoint inhibitors](https://onco.cc/technologies/checkpoint-inhibitor/)
- drugs: [Atezolizumab](https://onco.cc/drugs/atezolizumab/), [Avelumab](https://onco.cc/drugs/avelumab/), [Cemiplimab](https://onco.cc/drugs/cemiplimab/), [Dostarlimab](https://onco.cc/drugs/dostarlimab/), [Durvalumab](https://onco.cc/drugs/durvalumab/), [Ipilimumab](https://onco.cc/drugs/ipilimumab/), [Nivolumab](https://onco.cc/drugs/nivolumab/), [Pembrolizumab](https://onco.cc/drugs/pembrolizumab/), [Tremelimumab](https://onco.cc/drugs/tremelimumab/)
- institutions: [American Society of Clinical Oncology (ASCO)](https://onco.cc/institutions/asco/), [European Society for Medical Oncology (ESMO)](https://onco.cc/institutions/esmo/), [Society for Immunotherapy of Cancer](https://onco.cc/institutions/sitc/)
- terms: [Immune-related adverse events (irAEs)](https://onco.cc/terms/irae/), [Rechallenge and retreatment](https://onco.cc/terms/rechallenge/)
- key papers: [ASCO 2021 guideline: how to recognise and manage the immune-related side effects of checkpoint inhibitors](https://onco.cc/key-papers/paper-asco-irae-guideline-jco-2021/)

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