Myocarditis With Radiotherapy and Immunotherapy in Multiple Myeloma

Chang, Andrés; Nasti, Tahseen H.; Parashar, Susmita; Kaufman, Jonathan L.; Boise, Lawrence H.; Lonial, Sagar; Ahmed, Rafi; Nooka, Ajay K.

doi:10.1200/jop.18.00208

Cited by 11 publications

(9 citation statements)

References 4 publications

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“…Another research also highlighted the high mortality rate of severe ICIs-associated myocarditis [8]. However, the published articles about ICIs-related myocarditis are mainly from case reports [9,10] and clinical trials [11], which usually cannot detect the rare adverse drug reactions (ADRs) and reflect the real risk of ICIs-associated AEs because of inherent limitations of case reports and clinical trials (including limited sample size, missing follow-up information, and the like). Therefore, fatal ICIs-related myocarditis is necessary to be further investigated based on the data from the real-world scenario.…”

Section: Introductionmentioning

confidence: 99%

Immune checkpoint inhibitors-related myocarditis in patients with cancer: an analysis of international spontaneous reporting systems

Wang

Meng

et al. 2021

BMC Cancer

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Background Immune checkpoint inhibitors-induced myocarditis presents unique clinical challenges. Here, we assessed post-marketing safety of cytotoxic T-lymphocyte-associated protein-4 (CTLA-4), programmed cell death-1 (PD-1), and programmed death-ligand 1 (PD-L1) inhibitors by mining the real-world data reported in two international pharmacovigilance databases. Methods We analyzed immune checkpoint inhibitors (ICIs)-associated fatal adverse drug events (ADEs) reports from the US Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) collected from July 1, 2014 to December 31, 2019 and data from EudraVigilance (EV) database accessed on February 29, 2020. Three different data mining approaches were used to detect the signal of fatal myocarditis caused by ICIs. Results Based on 7613 ICIs-related ADEs reported to the EV database and 5786 ICIs-associated ADEs submitted to the FAERS database, the most frequently reported ADE was ipilimumab-related colitis. For myocarditis, nivolumab-associated myocarditis was the most common. Among the five fatal toxic effects associated with ICIs, the lethality rate of myocarditis was the highest. Therefore, we further analyzed ICI-associated myocarditis and found that elderly patients and male patients were more likely to develop ICIs-related myocarditis. The results of signal detection showed that the risk signal of avelumab-related myocarditis detected by reporting odds ratio (ROR) method and proportional reporting ratios (PRR) method was the highest, whereas the signal strength of ipilimumab-related myocarditis detected by Bayesian confidence propagation neural networks (BCPNN) method was the strongest. Conclusion The findings of this study indicated the potential safety issues of developing myocarditis when using ICIs, which were consistent with the results of previous clinical trials and could provide a reference for clinical workers when using ICIs.

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Section: Introductionmentioning

confidence: 99%

Immune checkpoint inhibitors-related myocarditis in patients with cancer: an analysis of international spontaneous reporting systems

Wang

Meng

et al. 2021

BMC Cancer

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“…Also, the common general presenting symptoms were fatigue, myalgia, general discomfort, or nausea, which are similar to what is reported in other studies. [7, 8] In addition to the non-specificity of clinical presentation which poses a challenge in the diagnosis, the median reporting time varies which adds another hurdle to diagnose a case of ICI-induced myocarditis. Our results showed the median time onset of symptoms after initiation of the therapy was 79.50 days, 16 days reported by Matznel et al, and 6 months reported in Dolldile et al cohort retrospective study and a year in Gallegos et al [10, 17, 44] Hence, clinicians should have a high index of suspicion when managing patients on an ICI treatment regimen even if the treatment was initiated over 6 months or a year ago and should be aware of the ICI cardiac adverse events and the need for prolonged cardiac monitoring.…”

Section: Discussionmentioning

confidence: 99%

Analysis of Corticosteroids in Immune Checkpoint Inhibitors (ICE) Induced Myocarditis – A Systematic Review of 352 Screened Articles

Sheikh

Patel

Nagpal³

et al. 2021

Preprint

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IntroductionImmune Checkpoint Inhibitors (ICI) are used as a single agent or as a combination therapies for early or late-stage malignancies. The common malignancies that ICI targets include the following: melanoma, lung cancer, renal cell carcinoma, and hematological malignancies such as Hodgkin’s lymphoma. ICI use is associated with many immune-related adverse events, and ICI-induced myocarditis is one of the rare and most severe AE with a high mortality rate. There are no consensus evidence-based treatment guideline; the expert recommendation is to use high-dose steroids. We aim in this review to assess the effectiveness of steroids in treating ICI-induced myocarditis.MethodsWe searched the following database Pubmed, Scopus, Cinhale, and Google Scholar, using the following keywords: ICI-induced myocarditis, treatment, steroid. We included articles in the English language, case reports, case series, and published in the last five years.Results352 articles were screened using PRISMA guidelines. After excluding the articles that were duplicate, irrelevant, and did not meet inclusion criteria, 35 articles with a total number of 50 patients were included. All patients treated with ICI either as a single or combination regimen. The onset of symptoms post initiation varied from one day to a year. 46 out of the 50 cases received high doses of Intravenous steroids as a loading dose followed by an oral or intravenous maintenance dose. Out of 50 patients 14 patients (28 %) died but 34 (68 %) patients survived, and 2 (4 %) patients data were not available. The mean age of the patients was 66.31 ± 14.071 (range 23-88 years), 29 were male (58%), 21 were female (42%). Most of the cases were from the USA (42%), followed by Australia (20 %), Japan (14%), Germany, France, and China (4%), Switzerland, Canada, and Spain (2%), and for (6%) cases. A total of 23 patients had cardiovascular comorbidities (46%), which were HTN (14 patients, 60.87%), hyperlipidemia (5 patients, 21.73%), and less than 1 % of patients had myocardial ischemia, congestive heart failure, atrial fibrillation, and peripheral vascular disease. While 26 patients (52%) had normal basal cardiac status.ConclusionOur results showed that high doses of steroids were effective in controlling cardiac myocyte inflammation and mortality by 28%. Race was not included in the analysis as it was not reported. More in – depth studies are needed to provide a broader representation of steroids in myocarditis.

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“…Similarly, combined anti-PD-1/anti-LAG-3 therapy in recent trials reported somewhat higher numbers of myocarditis as compared to single anti-PD-1 therapy (1.7 vs. 0.6%, respectively) ( Tawbi et al, 2022 ). With regards to other treatment modalities, there are several case-reports and studies describing cardiotoxicity, especially myocarditis, induced by combination or adjuvant therapy of ICI and radiotherapy or chemotherapy ( Semper et al, 2016 ; Chang et al, 2018 ; Banfill et al, 2021 ; Liang et al, 2021 ). Therefore, research into the different means of myocardial damage inflicted by the method of treatment and the combined effect of this in the case of combination therapy is important to further optimize prevention or treatment of cardiotoxicity.…”

Section: Cardiac Immune Checkpointsmentioning

confidence: 99%

The role of immune checkpoints in cardiovascular disease

et al. 2022

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Immune checkpoint inhibitors (ICI) are monoclonal antibodies which bind to immune checkpoints (IC) and their ligands to prevent inhibition of T-cell activation by tumor cells. Currently, multiple ICI are approved targeting Cytotoxic T-lymphocyte antigen 4 (CTLA-4), Programmed Death Protein 1 (PD-1) and its ligand PD-L1, and Lymphocyte-activation gene 3 (LAG-3). This therapy has provided potent anti-tumor effects and improved prognosis for many cancer patients. However, due to systemic effects, patients can develop immune related adverse events (irAE), including possible life threatening cardiovascular irAE, like atherosclerosis, myocarditis and cardiomyopathy. Inhibition of vascular IC is associated with increased atherosclerotic burden and plaque instability. IC protect against atherosclerosis by inhibiting T-cell activity and cytokine production, promoting regulatory T-cell differentiation and inducing T-cell exhaustion. In addition, PD-L1 on endothelial cells might promote plaque stability by reducing apoptosis and increasing expression of tight junction molecules. In the heart, IC downregulate the immune response to protect against cardiac injury by reducing T-cell activity and migration. Here, inhibition of IC could induce life-threatening T-cell-mediated-myocarditis. One proposed purpose behind lymphocyte infiltration is reaction to cardiac antigens, caused by decreased self-tolerance, and thereby increased autoimmunity because of IC inhibition. In addition, there are several reports of ICI-mediated cardiomyopathy with immunoglobulin G expression on cardiomyocytes, indicating an autoimmune response. IC are mostly known due to their cardiotoxicity. However, t his review compiles current knowledge on mechanisms behind IC function in cardiovascular disease with the aim of providing an overview of possible therapeutic targets in prevention or treatment of cardiovascular irAEs.

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Myocarditis With Radiotherapy and Immunotherapy in Multiple Myeloma

Cited by 11 publications

References 4 publications

Immune checkpoint inhibitors-related myocarditis in patients with cancer: an analysis of international spontaneous reporting systems

Immune checkpoint inhibitors-related myocarditis in patients with cancer: an analysis of international spontaneous reporting systems

Analysis of Corticosteroids in Immune Checkpoint Inhibitors (ICE) Induced Myocarditis – A Systematic Review of 352 Screened Articles

The role of immune checkpoints in cardiovascular disease

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