Fatal association of fulminant myocarditis and rhabdomyolysis after immune checkpoint blockade

Tomoaia, Raluca; Beyer, Ruxandra; Pop, Dana; Minciună, Ioan Alexandru; Dădârlat-Pop, Alexandra

doi:10.1016/j.ejca.2020.03.003

Cited by 7 publications

(5 citation statements)

References 5 publications

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“…In our systematic literature search, 71 full-texts of case reports or case series of patients with solid tumors who manifested neuromuscular or cardiac irAEs were selected, and data from 120 patients were extracted. 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 , 61 , 62 , 63 , 64 , 65 , 66 , 67 , 68 , 69 , 70 , 71 , 72 , 73 , 74 , 75 , 76 , 77 , ...…”

Section: Resultsmentioning

confidence: 99%

Neuromuscular and cardiac adverse events associated with immune checkpoint inhibitors: pooled analysis of individual cases from multiple institutions and literature

Boutros¹,

Bottini²,

Rossi³

et al. 2023

ESMO Open

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Section: Resultsmentioning

confidence: 99%

Neuromuscular and cardiac adverse events associated with immune checkpoint inhibitors: pooled analysis of individual cases from multiple institutions and literature

Boutros¹,

Bottini²,

Rossi³

et al. 2023

ESMO Open

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“…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].…”

Section: Resultsmentioning

confidence: 99%

“…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.…”

Section: Resultsmentioning

confidence: 99%

“…Most cases described lymphocytic infiltrate (which was positive for T‐cell markers, both CD4 and CD8) with CD68 positive macrophages. Variable extent of myocyte injury was described; only six cases [10, 12, 13, 24, 34, 35] described both myocyte injury, and inflammatory infiltrate consistent with the Dallas criteria for myositis and the World Heart Federation criteria for the diagnosis of acute myocarditis [41, 42]. Fukasawa et al reported the expression of human leukocyte antigen (HLA)‐ABC and HLA‐DR on myocardial cells in addition to the CD4 and CD8 T‐cell infiltrations [13].…”

Section: Resultsmentioning

confidence: 99%

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

et al. 2021

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Background. The development of immune checkpoint inhibitors (ICI) represents a paradigm shift in the treatment of cancers. Despite showing remarkable efficacy, these agents can be associated with life-threatening immunerelated adverse events. In recent years, several cases of myocarditis with myositis and/or myasthenia gravis overlap syndrome (IM3OS) have been reported. However, given the rarity, the clinical features and outcomes of these cases remain poorly understood. We, therefore, attempted to systematically review and summarize all cases of IM3OS reported in the literature. Methods. Studies reporting IM3OS were identified in Embase and MEDLINE. Only case reports and case series published in journals or presented at conferences were included. We conducted a systematic review according to the PRISMA Harms guidelines.Results. A total of 60 cases were eligible. The patients' median age was 71 years, and the majority (67%) were males; melanoma was the most common indication for ICI (38%). The most-reported symptom was fatigue (80%) and muscle weakness (78%). The median number of doses to the development of IM3OS was one. The average creatine kinase level was 9645 IU/L. Cardiac arrhythmias occurred in 67% of patients, and 18% had depressed ejection fraction. Initial treatment consisted of immunosuppression with high-dose steroids and supportive therapies. 60% of the patients died in hospital due to acute complications. Conclusion. IM3OS can be associated with significant mortality and morbidity. Prospective studies are needed to understand the optimal approach to diagnose and manage these patients and to develop biomarkers to predict the occurrence and severity of this rare but serious condition. The Oncologist ;9999:• •

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“…To date, the mechanisms and key players of ipilimumab-induced myocardial injuries are not completely understood [ 69 ]. Immune cells uptake and infiltration in heart tissues were always seen in human histological studies with high amounts of CD4+/CD8+ T lymphocytes and CD68+ cells [ 70 ]; this interaction involves some chemokines like Interleukin 1, 6, and 8 and chemokines that increase the granzyme B-mediated cytotoxicity driving cardiac injury [ 71 ]. Treatment with ipilmumab and other ICIs increase the cancer cell recognition of lymphocytes and their release of cytotoxic degranulation markers perforin and granzyme B [ 72 ].…”

Section: Discussionmentioning

confidence: 99%

NLRP3 as Putative Marker of Ipilimumab-Induced Cardiotoxicity in the Presence of Hyperglycemia in Estrogen-Responsive and Triple-Negative Breast Cancer Cells

Quagliariello

Laurentiis

Cocco

et al. 2020

IJMS

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Hyperglycemia, obesity and metabolic syndrome are negative prognostic factors in breast cancer patients. Immune checkpoint inhibitors (ICIs) have revolutionized cancer treatment, achieving unprecedented efficacy in multiple malignancies. However, ICIs are associated with immune-related adverse events involving cardiotoxicity. We aimed to study if hyperglycemia could affect ipilimumab-induced anticancer efficacy and enhance its cardiotoxicity. Human cardiomyocytes and estrogen-responsive and triple-negative breast cancer cells (MCF-7 and MDA-MB-231 cell lines) were exposed to ipilimumab under high glucose (25 mM); low glucose (5.5 mM); high glucose and co-administration of SGLT-2 inhibitor (empagliflozin); shifting from high glucose to low glucose. Study of cell viability and the expression of new putative biomarkers of cardiotoxicity and resistance to ICIs (NLRP3, MyD88, cytokines) were quantified through ELISA (Cayman Chemical) methods. Hyperglycemia during treatment with ipilimumab increased cardiotoxicity and reduced mortality of breast cancer cells in a manner that is sensitive to NLRP3. Notably, treatment with ipilimumab and empagliflozin under high glucose or shifting from high glucose to low glucose reduced significantly the magnitude of the effects, increasing responsiveness to ipilimumab and reducing cardiotoxicity. To our knowledge, this is the first evidence that hyperglycemia exacerbates ipilimumab-induced cardiotoxicity and decreases its anticancer efficacy in MCF-7 and MDA-MB-231 cells. This study sets the stage for further tests on other breast cancer cell lines and primary cardiomyocytes and for preclinical trials in mice aimed to decrease glucose through nutritional interventions or administration of gliflozines during treatment with ipilimumab.

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Fatal association of fulminant myocarditis and rhabdomyolysis after immune checkpoint blockade

Cited by 7 publications

References 5 publications

Neuromuscular and cardiac adverse events associated with immune checkpoint inhibitors: pooled analysis of individual cases from multiple institutions and literature

Neuromuscular and cardiac adverse events associated with immune checkpoint inhibitors: pooled analysis of individual cases from multiple institutions and literature

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

NLRP3 as Putative Marker of Ipilimumab-Induced Cardiotoxicity in the Presence of Hyperglycemia in Estrogen-Responsive and Triple-Negative Breast Cancer Cells

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