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Case Reports
. 2024;16(20-22):1203-1210.
doi: 10.1080/1750743X.2024.2427563. Epub 2024 Nov 16.

Fatal rhabdomyolysis and fulminant myocarditis with malignant arrhythmias after one dose of ipilimumab and nivolumab

Marko Kurnik  1 , Petra Kolar Kus  1 , Mihela Krepek  1 , Janko Vlaović  1 , Matej Podbregar  1   2
Affiliations
Case Reports

Fatal rhabdomyolysis and fulminant myocarditis with malignant arrhythmias after one dose of ipilimumab and nivolumab

Marko Kurnik et al. Immunotherapy. 2024.

Abstract

Immune checkpoint inhibitors (ICIs) related myocarditis is a rare complication of modern immunotherapy. It can present as an asymptomatic subclinical condition or full-blown fulminant myocarditis with malignant arrythmias and cardiogenic shock. Myositis/rhabdomyolysis and/or myasthenic symptoms can be present concomitantly. We present a case of fatal fulminant myocarditis presenting with cardiac arrythmias and severe systolic dysfunction, with accompanying rhabdomyolysis after the first dose of ipilimumab and nivolumab immunotherapy. First working diagnosis of subacute late presenting acute myocardial infarction (ACS) was incorrect and the correct diagnosis was established only after additional testing and consultation. Treatment consisted of high-dose corticosteroids, intravenous immunoglobulins, sedation with mechanical ventilation, antibiotic coverage, hemodialysis, and sustained low-efficiency daily diafiltration (SLEDD) with CytoSorb or TheraNova membranes, and intra-aortic balloon pump mechanical cardiac support. No tangible improvement in the condition was observed during the whole treatment period and the patient died on the sixth day of intensive care treatment.

Keywords: Chekpoint inhibitors; ICU; immune related adverse event; immunotherapy; mesothelioma; myocarditis; rhabdomyolysis.

Plain language summary

This case report describes a 77-year-old man who experienced a life-threatening autoimmune inflammation and diminished function of cardiac muscle (myocarditis) and breakdown of muscle cells (rhabdomyolysis), after receiving immunotherapy for pleural (membrane that surrounds the lungs) cancer (mesothelioma). He was initially thought of having a heart attack (cardiac infarction), and only further testing proved aforementioned autoimmune disease. Despite intensive treatment his condition worsened progressively. The disease was ultimately fatal.

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Conflict of interest statement

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Figures

Figure 1.
Figure 1.
Electrocardiogram (ECG) taken in emergency ward that warranted the diagnosis of subacute (late presenting) ST-segment elevation myocardial infarction (STEMI). Note extensive Q-waves in inferior and anterior leads, irregular QRS complex rhythm and absence of P-waves.
Figure 2.
Figure 2.
Transthoracic subcostal projections represent cardiac ventricle dimensions in systole. The snapshot on the left is from admission to intensive care unit (ICU). The snapshot on the right is from fourth day of ICU treatment. Dilatation of right ventricle is apparent. Additionally, please refer to videos in supplementary materials.
Figure 3.
Figure 3.
Chest X-ray taken after positioning intra-aortic balloon pump (additional correction was made after examining this X-ray). Also note the presence of central venous line in right subclavian vein, nasogastric tube, electrocardiogram leads and endotracheal tube. There are also signs of pleural effusion (blunting of the costophrenic angle), but were not present on pleural ultrasound. The X-ray was taken in supine position with 45° angle elevation.
See this image and copyright information in PMC

References

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    1. Thuny F, Alexandre J, Salem JE, et al. Management of immune checkpoint inhibitor-induced myocarditis: the French working group’s plea for a pragmatic approach. JACC CardioOncol. 2021;3(1):157–161. doi: 10.1016/j.jaccao.2020.12.001 - DOI - PMC - PubMed
    1. Lyon AR, Lopez-Fernandez T, Couch LS, et al. 2022 ESC guidelines on cardio-oncology developed in collaboration with the European hematology association (EHA), the European society for therapeutic radiology and oncology (ESTRO) and the International cardio-oncology society (IC-OS). Eur Heart J. 2022;43(41):4229–4361. - PubMed

    2. •• Comprehensive review article by European Society of Cardiology with information on many immune related adverse events. Specific information relating myocarditis can be found on page 4286 (subsection 6.1.3.).

    1. Kurnik M, Peter F, Matej P.. Tocilizumab and CytoSorb for delayed severe cytokine release syndrome after ipilimumab plus nivolumab immunotherapy. Immunotherapy. 2024;1–11. - PMC - PubMed

    2. • Previous case report from our intensive care unit pertaining a case of severe cytokine release syndrome following nivolumab and ipilimumab immunotherapy. Establishing the correct diagnosis was also challenging.

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