e15116 Background: Monoclonal antibodies against the immune checkpoint inhibitors (ICI) programmed cell death protein-1 (PD-1), its ligand (PD-L1) and cytotoxic T-lymphocyte associated protein 4 (CTLA4) have had a transformative effect on the field of oncology. Autoimmune myocarditis (AIM) is a rare but potentially severe complication associated with these medications, without specific management guidelines. The aim of this observational report is to present four cases of AIM following ICI and propose a detection and treatment strategy. Methods: Four patients who received anti-PD-1 or anti-PD-L1 immune checkpoint inhibitors (ICI) developed severe cardiac manifestations within two weeks to several months after initiation. Demographic, historical, laboratory, and imaging data were collected by retrospective chart review. Results: Manifestations included LV systolic dysfunction, ventricular arrhythmias, and elevated cardiac enzymes. Myocardial ischemia was ruled out by coronary catheterization. Abnormal myocardial tissue characteristics on CMRI and biopsy were used to establish the diagnosis of myocarditis. Patients had endocrine, rheumatologic and neurologic irAEs (Table) and were managed by a multi-disciplinary team including oncology, rheumatology and cardiology. Management included prompt administration of high-dose steroids with rapid taper. Steroid sparing and escalation therapies included mycophenolate mofetil, methotrexate, rituximab, abatacept (CTLA4 agonist), as well as plasma exchange. This combination of tiered therapies resulted in substantial improvement in AIM. Conclusions: Clinical improvements seen in these cases highlight potential key elements for controlling autoimmune myocarditis response to ICI. We propose rapid diagnosis including CMRI and biopsy and initiation of high dose prednisone. We also recommend prompt initiation of steroid sparing agent within one month of diagnosis. Importantly, these patients should be managed by a multi-disciplinary team. [Table: see text]