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Myocarditis from Immune Checkpoint Inhibitors Potentially Mitigated by Early Corticosteroid

Key findings

  • Investigators reviewed 126 consecutive patients from an international, multicenter registry of cancer patients treated with corticosteroids for myocarditis associated with immune checkpoint inhibitor therapy
  • There was a graded reduction in the risk of major adverse cardiovascular events as the initial steroid dose increased and the time of initiation after admission shortened
  • In an analysis that considered both time of initiation and initial dosage, the use of high-dose steroids (methylprednisolone equivalent of 1,000 mg/day) did not overcome the effect of initiating steroids later than 24 hours after admission
  • It follows that starting non–high-dose steroids within 24 hours of admission may lead to a better outcome than giving high-dose corticosteroids later

Myocarditis associated with immune checkpoint inhibitor (ICI) therapy for cancer is uncommon but can be fulminant; up to 50% of affected patients die. Corticosteroids are the first-line treatment, but because ICIs are rather new, data are limited on what the initial dose should be and how soon steroids should be initiated. Indeed, current guidelines from major societies vary significantly in their recommendations for the optimum dose of corticosteroids.

Lili Zhang, MD, ScM, former fellow at the Cardiovascular Imaging Center at Massachusetts General Hospital and now the director of the Cardio-Oncology Program at Montefiore Medical Center, and Tomas G. Neilan, MD, MPH, director of the Cardio-Oncology Program in the Corrigan Minehan Heart Center, and colleagues recently investigated these questions by reviewing an international registry. In a research letter in Circulation, they report that a higher initial dose of corticosteroid and an earlier initiation were associated with improved cardiac outcomes.

Study Details

The researchers retrospectively collected data on 126 consecutive patients hospitalized with ICI-associated myocarditis at any of 23 centers. They were categorized as having received low-dose (<60 mg/day), intermediate-dose (60–500 mg/day) or high-dose (501–1,000 mg/day) corticosteroids based on the methylprednisolone equivalent administered on the first day of treatment.

Major cardiovascular adverse events (MACE) were defined as the composite of cardiovascular death, cardiac arrest, cardiogenic shock and complete heart block requiring a pacemaker.

Timing of Steroid Initiation

Patients who received steroids within 24 hours after admission were less likely to:

  • Have persistent troponin elevation at discharge (32%) than those first treated between 24 hours and 72 hours (67%) or after 72 hours (41%; P = .03)
  • Develop MACE (7%) than those treated between 24 hours and 72 hours (34%) or after 72 hours (85%; P < .001)

Compared with after 72 hours, initiation of corticosteroids within 24 hours was associated with a lower risk of MACE (adjusted HR, 0.03; 95% CI, 0.004–0.23; P = .001) as was initiation between 24 and 72 hours (aHR, 0.30; 95% CI, 0.12–0.73; P = .008).

Effects of Dosage Level

  • There was an inverse relationship between initial steroid dose and MACE: low dose, 62%; intermediate dose, 55%; high dose, 22% (P < .001)
  • Compared with low-dose steroids, high-dose therapy was associated with a 73% lower risk of MACE (aHR, 0.27; 95% CI, 0.09–0.84; P = .02)

Timing and Dosage Considered Together

In a separate analysis, patients were categorized into six groups according to both dose and timing of steroid: high-dose steroid (methylprednisolone equivalent ≥1,000 mg/day) initiated within 24 hours after admission, non–high dose initiated within 24 hours, high-dose initiated within 24–72 hours, non–high dose initiated within 24–72 hours, etc.

Regardless of dosage, patients receiving steroids within 24 hours had the best MACE-free survival rates and those receiving steroids after 72 hours had the worst.

Definitive Evidence Still Needed

Because this was a retrospective observational study, the benefit of early, intensive steroid dosing for patients with ICI-associated myocarditis is still unproven. It also remains to be clarified whether high-dose corticosteroids negatively affect patients' chances of surviving their cancer.

less risk of major cardiovascular events in patients with myocarditis associated with checkpoint inhibitors when steroids were started within 24 hours after admission

less risk of major cardiovascular events in patients with myocarditis associated with checkpoint inhibitors when the initial steroid dose was 501–1,000 mg/day

Learn more about the Cardio-Oncology Program at Mass General

Refer a patient to the Corrigan Minehan Heart Center

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