1183 Immune checkpoint therapy (ICT) rechallenge after immune-mediated myocarditis

<h3>Background</h3> Immune checkpoint therapies (ICTs) improve survival in subsets of cancer patients but can also induce serious immune-related adverse events (irAEs), such as myocarditis. ICT-induced myocarditis, while rare, is associated with significant mortality rates of 25–50% and often necessitates discontinuation of treatment.¹ Evidence suggests that patients with other irAEs can be safely rechallenged with ICTs, which may lead to improved antitumor responses.^{2 3} Following resolution of myocarditis, data are limited on safety and efficacy of ICT rechallenge. <h3>Hypothesis</h3> We hypothesized that ICT rechallenge after immune-mediated myocarditis would be safe in a subset of patients. <h3>Methods</h3> A single-center retrospective cohort study of patients with diagnosis of immune-mediated myocarditis according to Bonaca criteria⁴ between 1/2011 and 8/2021 was conducted. Those rechallenged ICT following immune-mediated myocarditis were reviewed. Demographics and clinical outcomes data were reviewed. <h3>Results</h3> A total of 103 patients with immune-mediated myocarditis were reviewed, with a median follow-up of 12.0 months (95% CI: 9.4 – 16.7 mo) and a mortality rate of 51% (52/103). Sixteen deaths were attributed to myocarditis. Median age was 72 years (IQR: 63 - 78), and 70% were male. The most common cancers were renal cell carcinoma (RCC) (n=23; 22%), melanoma (n=20; 19%), and lung (n=18; 17%). After resolution of myocarditis, 46% of patients (47/103) resumed anti-cancer therapy. Median time to subsequent therapy was 63 days (IQR: 31 - 198). Six patients (Grade 1 myocarditis [n=4]; Grade 2 [n=1]; Grade 4 [n=1]) were rechallenged with ICT (table 1). After rechallenge, three of 6 patients (50%) experienced subsequent irAEs , with no grade 3 or 4 events reported. Median time to development of irAEs from ICT rechallenge was 111 days (range: 56 - 153 days). Two patients achieved prolonged objective radiographic response (table 1). <h3>Conclusions</h3> A subset of patients with ICT-induced myocarditis were safely rechallenged with ICTs without subsequent severe irAEs. Durable responses were observed in a subset following rechallenge. Future studies will need to identify patients appropriate for rechallenge following severe irAEs such as myocarditis. <h3>References</h3> Palaskas N, Lopez-Mattei J, Durand JB, Iliescu C, Deswal A. Immune checkpoint inhibitor myocarditis: pathophysiological characteristics, diagnosis, and treatment. <i>J Am Heart Assoc</i>. 2020;<b>9</b>(2):e013757. doi:10.1161/JAHA.119.013757. Abou Alaiwi S, Xie W, Nassar AH, <i>et al</i>. Safety and efficacy of restarting immune checkpoint inhibitors after clinically significant immune-related adverse events in metastatic renal cell carcinoma. <i>J Immunother Cancer</i>. 2020;<b>8</b>(1). doi:10.1136/jitc-2019-000144. Ravi P, Mantia C, Su C, <i>et al</i>. Evaluation of the safety and efficacy of immunotherapy rechallenge in patients with renal cell carcinoma.<i> JAMA Oncol</i>. 2020;<b>6</b>(10):1606–10. doi:10.1001/jamaoncol.2020.2169. Bonaca MP, Olenchock BA, Salem JE, <i>et al</i>. Myocarditis in the setting of cancer therapeutics: proposed case definitions for emerging clinical syndromes in cardio-oncology. <i>Circulation</i>. 2019;<b>140</b>(2):80–91. doi:10.1161/CIRCULATIONAHA.118.034497.