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A case of severe immune-related adverse events, myocarditis with myositis, and myasthenia gravis overlap syndrome following adjuvant nivolumab administration for muscle-invasive bladder cancer

Kamikawa, Hiroki ; Matsukawa, Yoshihisa ; Nishii, Hisae ; Naito, Yushi ; Obara, Kazuki LU orcid ; Sahashi, Kentaro ; Morimoto, Ryota ; Matsuo, Kazuna ; Ishida, Shohei and Inoue, Satoshi , et al. (2025) In Nagoya journal of medical science 87. p.156-162
Abstract

Herein, we present a case of severe immune-related adverse events (irAEs), myocarditis with myositis, and myasthenia gravis overlap syndrome (IM3OS) in a patient receiving an immune checkpoint inhibitor (ICI), as adjuvant therapy after surgery for muscle-invasive bladder cancer. An 80-year-old woman who had undergone a total cystectomy for bladder cancer presented with ptosis, diplopia, and paralysis 18 days after receiving nivolumab, an anti-programmed cell death-1 (PD-1) monoclonal antibody, as adjuvant therapy for the first time. Initial testing revealed positive findings on the ice pack test; elevated troponin, creatine kinase, and aldolase levels; and an abnormal electrocardiogram, suggesting that the patient had developed... (More)

Herein, we present a case of severe immune-related adverse events (irAEs), myocarditis with myositis, and myasthenia gravis overlap syndrome (IM3OS) in a patient receiving an immune checkpoint inhibitor (ICI), as adjuvant therapy after surgery for muscle-invasive bladder cancer. An 80-year-old woman who had undergone a total cystectomy for bladder cancer presented with ptosis, diplopia, and paralysis 18 days after receiving nivolumab, an anti-programmed cell death-1 (PD-1) monoclonal antibody, as adjuvant therapy for the first time. Initial testing revealed positive findings on the ice pack test; elevated troponin, creatine kinase, and aldolase levels; and an abnormal electrocardiogram, suggesting that the patient had developed ICI-related myocarditis, myositis, and myasthenia gravis. Despite treatment with intravenous immunoglobulin (IVIG) and high-dose corticosteroids, her condition worsened, leading to a complete atrioventricular block. After cardiac pacemaker insertion and intensive treatment with repeated high-dose corticosteroids, IVIG, plasma exchange, and tacrolimus, left ventricular function and myositis symptoms improved. However, the patient developed a respiratory infection and renal failure, leading to death on day 99. Although ICIs are considered relatively safe with few side effects, they can cause serious complications and lead to death. In particular, when severe irAEs occur in multiple organs, such as IM3OS, the prognosis is poor. Although IM3OS has no specific diagnostic biomarker, making early detection difficult, clinicians should always pay attention to patient symptoms when using ICI and evaluate other pathologies with IM3OS when conditions such as myositis or myocarditis are suspected. Further research is needed to elucidate the pathophysiology and risk factors of IM3OS.

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publishing date
type
Contribution to journal
publication status
published
keywords
Humans, Female, Urinary Bladder Neoplasms/drug therapy, Myocarditis/chemically induced, Aged, 80 and over, Myositis/chemically induced, Myasthenia Gravis/chemically induced, Nivolumab/adverse effects, Immune Checkpoint Inhibitors/adverse effects
in
Nagoya journal of medical science
volume
87
pages
156 - 162
publisher
Nagoya University
external identifiers
  • scopus:85219472094
  • pmid:40255993
ISSN
0027-7622
DOI
10.18999/nagjms.87.1.156
language
English
LU publication?
no
id
f5202831-a073-426c-a1cf-b992da06c0b0
date added to LUP
2026-04-03 11:20:24
date last changed
2026-10-05 20:19:24
@article{f5202831-a073-426c-a1cf-b992da06c0b0,
  abstract     = {{<p>Herein, we present a case of severe immune-related adverse events (irAEs), myocarditis with myositis, and myasthenia gravis overlap syndrome (IM3OS) in a patient receiving an immune checkpoint inhibitor (ICI), as adjuvant therapy after surgery for muscle-invasive bladder cancer. An 80-year-old woman who had undergone a total cystectomy for bladder cancer presented with ptosis, diplopia, and paralysis 18 days after receiving nivolumab, an anti-programmed cell death-1 (PD-1) monoclonal antibody, as adjuvant therapy for the first time. Initial testing revealed positive findings on the ice pack test; elevated troponin, creatine kinase, and aldolase levels; and an abnormal electrocardiogram, suggesting that the patient had developed ICI-related myocarditis, myositis, and myasthenia gravis. Despite treatment with intravenous immunoglobulin (IVIG) and high-dose corticosteroids, her condition worsened, leading to a complete atrioventricular block. After cardiac pacemaker insertion and intensive treatment with repeated high-dose corticosteroids, IVIG, plasma exchange, and tacrolimus, left ventricular function and myositis symptoms improved. However, the patient developed a respiratory infection and renal failure, leading to death on day 99. Although ICIs are considered relatively safe with few side effects, they can cause serious complications and lead to death. In particular, when severe irAEs occur in multiple organs, such as IM3OS, the prognosis is poor. Although IM3OS has no specific diagnostic biomarker, making early detection difficult, clinicians should always pay attention to patient symptoms when using ICI and evaluate other pathologies with IM3OS when conditions such as myositis or myocarditis are suspected. Further research is needed to elucidate the pathophysiology and risk factors of IM3OS.</p>}},
  author       = {{Kamikawa, Hiroki and Matsukawa, Yoshihisa and Nishii, Hisae and Naito, Yushi and Obara, Kazuki and Sahashi, Kentaro and Morimoto, Ryota and Matsuo, Kazuna and Ishida, Shohei and Inoue, Satoshi and Miyagi, Shohei and Sakakibara, Ayako and Katsuno, Masahisa and Karube, Kennosuke and Akamatsu, Shusuke}},
  issn         = {{0027-7622}},
  keywords     = {{Humans; Female; Urinary Bladder Neoplasms/drug therapy; Myocarditis/chemically induced; Aged, 80 and over; Myositis/chemically induced; Myasthenia Gravis/chemically induced; Nivolumab/adverse effects; Immune Checkpoint Inhibitors/adverse effects}},
  language     = {{eng}},
  pages        = {{156--162}},
  publisher    = {{Nagoya University}},
  series       = {{Nagoya journal of medical science}},
  title        = {{A case of severe immune-related adverse events, myocarditis with myositis, and myasthenia gravis overlap syndrome following adjuvant nivolumab administration for muscle-invasive bladder cancer}},
  url          = {{http://dx.doi.org/10.18999/nagjms.87.1.156}},
  doi          = {{10.18999/nagjms.87.1.156}},
  volume       = {{87}},
  year         = {{2025}},
}