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Rarely, immunotherapy inflames the heart muscle. It usually starts in the first three months and can be fatal, so new chest pain, breathlessness, palpitations, fainting, or new muscle weakness, drooping eyelids or double vision need urgent assessment. It is treated in hospital with very high-dose steroids straight away.
Uncommon (about 1% in an eight-centre registry) but with high mortality: 50% of patients with myocarditis died in one retrospective series, and it clusters with myositis and myasthenia gravis, so suspicion of one should prompt a search for all three (SITC 2021). Median onset 34 days after starting. Troponin is raised in 94% and the ECG abnormal in 89%, while ejection fraction is normal in about half.
SITC 2021: consider myocarditis in anyone with new cardiac symptoms, arrhythmia, heart block or a raised troponin who has had a checkpoint inhibitor in the past 12 weeks; admit, involve cardiology, and obtain ECG, troponin and cardiac MRI (with or without endomyocardial biopsy), plus the shared myositis and myasthenia panel. Give methylprednisolone 1000 mg IV daily for 3 to 5 days as soon as the diagnosis is likely, until troponin normalises, then a 4 to 6 week prednisone taper; seriously consider permanent discontinuation. If there is no response within 24 hours add antithymocyte globulin, mycophenolate mofetil, abatacept or alemtuzumab (LE: 4); avoid infliximab (LE: 4). Manage in a coronary care unit with temporary pacing available. A retrospective study found steroids within 24 hours of admission were followed by fewer major cardiac events than later steroids.
ASCO 2021 makes cardiac toxicity one of the exceptions to continuing treatment for grade 1 toxicity. The ESC 2022 and ESC 2025 guidelines could not be read here.
Why: Myocarditis can deteriorate within hours and is often fatal if missed.
“A diagnosis of ICI-induced myocarditis should be considered in any patient developing new cardiac symptoms, new cardiac arrhythmias, new heart blocks, or cardiac lab findings (eg, asymptomatic troponin elevation) who has received an ICI therapy in the past 12 weeks. Suspicion of ICI-induced myocarditis should trigger hospital admittance and consultation with a cardiologist.”
Why: Troponin and ECG are abnormal in most cases; MRI or biopsy confirms the diagnosis.
“Patients with suspected ICI-induced myocarditis should undergo cardiac MRI if available (with or without right heart catheterization and myocardial biopsy), EKG, and testing for serum troponin levels.”
Why: The three conditions often occur together, and each raises the danger of the others.
“Should have testing including erythrocyte sedimentation rate (ESR), C reactive protein (CRP), creatine kinase (CK), antibody tests (acetylcholine, muscle-specific kinase (MusK), striational), aldolase, troponin, EKG, nerve conduction, and electromyography (EMG).”
Why: Early high-dose steroids were followed by fewer serious heart events than delayed treatment.
“Patients with suspected ICI-induced myocarditis should receive high-dose corticosteroids (1000 mg methylprednisolone IV or equivalent daily for 3–5 days, until troponin normalizes) as soon as possible once the diagnosis is considered likely, followed by 4–6 weeks 1–2 mg/kg prednisone taper.”
Why: Restarting risks a recurrence of a condition with high mortality.
“Permanent discontinuation of ICI therapy should be seriously considered.”
Why: Steroid-resistant myocarditis needs a second immunosuppressant quickly.
“If signs or symptoms do not respond to corticosteroid therapy within 24 hours, additional therapies such as ATG, mycophenolate mofetil, abatacept, or alemtuzumab should be considered as additional treatment”
Why: In one study infliximab was linked to a higher risk of cardiovascular death.
“Caution is advised against the use infliximab for steroid-refractory myocarditis”
Why: Heart block and dangerous rhythms can appear suddenly.
“Management of cardiac irAEs should take place in a coronary care unit, with temporary pacemaker support available for rapid access if indicated.”
Why: Overlapping myositis or myasthenia can weaken the breathing muscles.
“Should receive frequent pulmonary assessment in addition to typical irAE treatment (ie, corticosteroids).”
How care is usually carried out, read from the guidelines and standards cited. Your own team's protocol and their judgement come first; this page is for understanding it, not for doing it yourself.
Of the guidelines that could be read, SITC 2021 is the only one with a myocarditis protocol: admission, cardiology, ECG, troponin and cardiac MRI; methylprednisolone 1000 mg daily for 3 to 5 days as early as possible; serious consideration of permanent discontinuation; second-line antithymocyte globulin, mycophenolate, abatacept or alemtuzumab within 24 hours if there is no response (LE: 4), and caution against infliximab (LE: 4). Every recommendation rests on retrospective series and case reports; there are no randomised trials. ASCO 2021 (abstract) agrees that cardiac toxicity is not one where treatment continues at grade 1. The 2022 ESC cardio-oncology guideline, the 2025 ESC myocarditis guideline and ESMO 2022 could not be read, so whether they differ on dose, timing or the second-line agent is not stated here.
SITC, Journal for ImmunoTherapy of Cancer 2021 · ASCO, Journal of Clinical Oncology 2021 · European Society of Cardiology, European Heart Journal 2022 · European Society of Cardiology, European Heart Journal 2025 · ESMO, Annals of Oncology 2022
Where it differs: Considers a baseline ECG for patients at higher risk of myocarditis (cardiac disease, diabetes, combined PD-(L)1 and CTLA-4 blockade) and a baseline troponin, so that later results can be compared; SITC notes there is no evidence that troponin screening in patients without symptoms improves outcome.
Evidence: Expert consensus; no level of evidence printed.
| Recommendation | Grade, as printed | Source |
|---|---|---|
| Second-line antithymocyte globulin, mycophenolate mofetil, abatacept or alemtuzumab if no response in 24 hours | LE: 4 | SITC, Journal for ImmunoTherapy of Cancer 2021 |
| Caution against infliximab in steroid-refractory myocarditis | LE: 4 | SITC, Journal for ImmunoTherapy of Cancer 2021 |
| Methylprednisolone 1000 mg daily for 3 to 5 days, and admission with cardiology | not graded (expert consensus) | SITC, Journal for ImmunoTherapy of Cancer 2021 |
| Cardiac toxicity is an exception to continuing treatment at grade 1 “in general, ICPi therapy should be continued with close monitoring for grade 1 toxicities, except for some neurologic, hematologic, and cardiac toxicities.” | expert consensus | ASCO, Journal of Clinical Oncology 2021 |
Two technology pages on OnCo cite this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing pages listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.
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.
Shares Methylprednisolone, Baseline tests and monitoring before and during checkpoint inhibitor treatment, ASCO 2021 guideline: how to recognise and manage the immune-related side effects of checkpoint inhibitors, Society for Immunotherapy of Cancer and the tags protocol, irae, acute-oncology.
Shares Methylprednisolone, Baseline tests and monitoring before and during checkpoint inhibitor treatment, ASCO 2021 guideline: how to recognise and manage the immune-related side effects of checkpoint inhibitors, Society for Immunotherapy of Cancer and the tags protocol, irae, acute-oncology.
Shares Baseline tests and monitoring before and during checkpoint inhibitor treatment, ASCO 2021 guideline: how to recognise and manage the immune-related side effects of checkpoint inhibitors, Society for Immunotherapy of Cancer, Avelumab and the tags protocol, irae, acute-oncology.
Shares Baseline tests and monitoring before and during checkpoint inhibitor treatment, ASCO 2021 guideline: how to recognise and manage the immune-related side effects of checkpoint inhibitors, Society for Immunotherapy of Cancer, Avelumab and the tags protocol, irae, acute-oncology.
Shares Baseline tests and monitoring before and during checkpoint inhibitor treatment, ASCO 2021 guideline: how to recognise and manage the immune-related side effects of checkpoint inhibitors, Society for Immunotherapy of Cancer, Avelumab and the tags protocol, irae.
Shares Methylprednisolone, ASCO 2021 guideline: how to recognise and manage the immune-related side effects of checkpoint inhibitors, Society for Immunotherapy of Cancer, Avelumab and the tags protocol, irae.
Shares Baseline tests and monitoring before and during checkpoint inhibitor treatment, ASCO 2021 guideline: how to recognise and manage the immune-related side effects of checkpoint inhibitors, Society for Immunotherapy of Cancer, Avelumab and the tags protocol, irae, acute-oncology.
Shares Baseline tests and monitoring before and during checkpoint inhibitor treatment, Society for Immunotherapy of Cancer, Avelumab, Tremelimumab and the tags protocol, irae.