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Abstract
BackgroundImmune checkpoint inhibition is part of standard systemic management for many advanced malignancies. Toxicities from this treatment approach are unpredictable, though usually reversible with management per established guidelines. Some patients suffer major morbidity and treatment-related mortality from these agents in an unpredictable manner. Cardiac and neurologic complications are rare, but can result in serious clinical consequences.MethodsWe describe the presentation, management, and outcomes of eight sequential cases of combined cardiac and neurologic toxicities resulting in severe illness and demonstrating lack of rapid response to immunosuppression.ResultsOur cohort consisted of six males and two females with an average age of 73.5 years (61–89 years). There were four patients with melanoma, and one patient each with urothelial carcinoma, renal cell carcinoma, breast cancer, and non-small cell lung cancer. Four patients received combination immunotherapy and four patients received monotherapy. The median time to presentation from treatment initiation was 27 days (11–132 days). All patients had a cardiovascular and neurologic toxicity, and most had hepatitis and myositis. The cardiac signs and symptoms were the prominent initial features of the clinical presentation. Each patient was managed by a multidisciplinary team and received a range of immunosuppressive agents. All patients died as a consequence of the immune related adverse events.ConclusionsThe evaluation of patients with cardiac adverse events from immunotherapy, should include assessment of overlapping toxicities such as myasthenia gravis and myositis. Providers should be aware of the potential for an extended duration of disability and slow improvement for certain toxicities as these expectations may factor prominently in goals of care decisions.
Highlights
Immune checkpoint inhibition is part of standard systemic management for many advanced malignancies
Clinical and oncologic data Eight successive cases of combined neurologic and cardiac toxicities presented to the University of Virginia (UVA) Health System, including four patients who received oncologic care outside of our institution and were transferred for toxicity management (Table 1)
Four patients received anti-programmed cell death-1 (PD-1) monotherapy, including one patient being treated in the adjuvant setting for melanoma
Summary
Immune checkpoint inhibition is part of standard systemic management for many advanced malignancies. Toxicities from this treatment approach are unpredictable, though usually reversible with management per established guidelines. Patient exposure to ICI will continue to increase, as there are several new agents in development. Less common irAEs, such as cardiac and neurologic toxicities, have emerged with increasing utilization. There are reports of fulminant fatal cardiac toxicity, electrical dysfunction, acute coronary syndrome, pericarditis, and acute systolic heart failure occurring after ICI therapy [7,8,9,10,11,12,13]. Defining the frequency and patterns of cardiac toxicity from ICI therapy is an area of active investigation [14]. A 2019 pharmacovigilance study reported an increased incidence of myasthenia gravis (MG), encephalitis, peripheral neuropathy and meningitis with use of ICI therapy [15]
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