Fatal Autoimmune Storm After a Single Cycle of Anti-PD-1 Therapy

Abstract

As immunotherapy agents are incorporated into the routine oncological practice, the number of patients at the risk of immune-related adverse events has increased dramatically. However, the prompt identification and effective management of severe autoimmune complications remain a challenge. We report the case of a patient with metastatic lung adenocarcinoma who experienced a fatal autoimmune storm 3 weeks after the first dose of anti-programmed death receptor-1 (PD-1) agent pembrolizumab, which included thyroiditis, hepatitis, myositis, myocarditis, pneumonitis, and myasthenia gravis. Aggressive autoimmunity was supported by extensive T-cell and macrophage tissue infiltrates and autoantibody positivity. Remarkably, no residual tumor was found at autopsy. This case illustrates the potential harm caused by immunotherapy and our limited knowledge on its prevention, treatment, and association to antitumor efficacy.

Immune Checkpoint Inhibitor–Induced Myocarditis with Myositis/Myasthenia Gravis Overlap Syndrome: A Systematic Review of Cases

“…There was no consistent pattern of preexisting autoimmune conditions—only one patient had a prior autoimmune disease [5]. Twenty‐two patients were reported to have concomitant myasthenia gravis [4, 6–18]. The median number of doses to the development of IM3OS was one.…”

“…Todo et al described a case of seronegative myasthenia gravis, although electrodiagnostic testing was reported to be negative [27]. Anti‐AChR antibodies were reported to be positive in the majority of cases in which concurrent myasthenia gravis was diagnosed [4, 6, 7, 10–12, 21, 28].…”

“…Eighteen cases reported muscle biopsy results, with most cases describing myofiber necrosis and atrophy with lymphocytic (predominantly CD8 + T cell) and macrophage infiltrates [5, 9, 11, 12, 20, 21, 23, 24, 34–39]. One case reported negative inflammatory cell infiltration or necrosis [24].…”

“…One case reported negative inflammatory cell infiltration or necrosis [24]. Fifteen cases had cardiac biopsies [10, 12, 13, 18, 22, 24, 31, 33–36, 39, 40]. Most cases described lymphocytic infiltrate (which was positive for T‐cell markers, both CD4 and CD8) with CD68 positive macrophages.…”

A systematic review of myasthenia gravis complicated with myocarditis

“…Myositis may either occur concurrently with, or precede the development of, MG. Conversely, myocarditis always seems to follow MG (Shah et al., 2015). Importantly, a previous study found that myositis and/or myocarditis occur concomitantly with MG, and are frequently related to poor outcomes (Fuentes‐Antrás et al., 2020). There were 35 cases of MG complicated with myocarditis in our review, and the death group accounted for 57.14% (20/35).…”