Abstract

Abstract Background: Immune checkpoint inhibitors (ICI) have improved survival in various malignancies but are associated with significant immune-related adverse events (irAE). Up to 2% of patients on ICI develop ICI-myocarditis, which is associated with significant mortality. Treatment guidelines for ICI-myocarditis are limited. The initial treatment starts with high dose glucocorticoids, but the subsequent lines of treatment remain ill-defined. Methods: We retrospectively identified patients at our institution from 2021 onwards who were treated for ICI-myocarditis and who had an inadequate response to steroid treatment (thus steroid refractory). Baseline characteristics, laboratory and imaging data, and outcomes were reviewed. Results: Of the 34 patients diagnosed with ICI-myocarditis, 18 (53%) were steroid refractory. Amongst the 18, 11 were female and 7 were male, with a mean age of 73. Cancer types included head and neck, thoracic, urologic, gynecologic, and gastrointestinal. Patients had received a median of 2 ICI doses prior to myocarditis presentation. Thirteen (72%) patients had prior or concurrent irAE, most commonly neurologic or neuromuscular such as myasthenia gravis/myositis (44%) or hepatitis (33%). For initial treatment, 14 (41%) patients received a max dose of methylprednisolone 1g/day, while 4 (12%) received smaller doses (less than 500mg/day). Following steroids, the most common next treatment was mycophenolate mofetil (MMF) for 9 (50%), IVIG for 6 (33%), and Abatacept for 3 patients (17%). MMF was most often added and uptitrated to wean steroids, with 8 (44%) patients being able to be tapered off after a median duration of 112 days. IVIG was more commonly used for patients with concomitant neurologic symptoms while Abatacept was more commonly used for patients presenting with grade IV toxicities. The most encountered side effects following steroids were hyperglycemia, weight gain, adrenal insufficiency, and myopathy and following MMF were cytopenias and hypertension. The median survival since myocarditis diagnosis was 412 days. The patient with the longest documented survival of 645 days received IVIG and then MMF following steroids. Two patients with severely immunosuppression-resistant myocarditis responded well to tofacitinib, with one patient living 521 days after diagnosis (after methylprednisolone, IVIG, MMF, Abatacept, Tofacitinib) and one still alive more than 400 days after diagnosis (after methylprednisolone, MMF, Abatacept, IVIG, Infliximab, Tofacitinib). Conclusion: Steroid-refractory ICI-associated myocarditis can be responsive to other immunosuppression agents. Our case series, one of the largest studies of this population, highlights their effectiveness and the populations they can cater to. Adjunctive treatments for ICI-myocarditis require further study to identify right doses and order of treatment. Citation Format: Ritujith Jayakrishnan, Samantha Brongiel, Darren Luon, Stephanie Halene, Jennifer M. Kwan. Treatment of steroid-refractory immune checkpoint inhibitor-associated myocarditis: A case series of 18 patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 2480.

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