Evolution of Immune Checkpoint Blockade–Induced Myocarditis Over 2 Years

Norwood, Timothy G.; Lenneman, Carrie; Westbrook, Brian C.; Litovsky, Silvio; McKee, RN Svetlana B.; Conry, Robert M.

doi:10.1016/j.jaccas.2019.11.076

Cited by 7 publications

(6 citation statements)

References 8 publications

(10 reference statements)

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“… 9 , 10 Furthermore, one case report showed that rechallenge with ICIs induced a treatment-refractory exacerbation of myocarditis. 8 Thus, physicians should be sufficiently vigilant to avoid overlooking mild or even asymptomatic CV–irAEs. Another key aspect of the ASCO definition of CV–irAEs is its inclusion of heart failure.…”

Section: Discussionmentioning

confidence: 99%

Incidence, Clinical Characteristics, and Predictors of Cardiovascular Immune-Related Adverse Events Associated with Immune Checkpoint Inhibitors

et al. 2022

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Background Cardiovascular immune-related adverse events (CV–irAEs) associated with immune checkpoint inhibitors (ICIs) may have been underreported given that most previous reports were retrospective. We aimed to evaluate the incidence, clinical characteristics, and predictors of CV–irAEs and determine the feasibility of serial cardiac monitoring using a combination of B-type natriuretic peptide, cardiac troponin T, and electrocardiogram for the prediction of future symptomatic (grade ≥2) CV–irAEs. Materials and Methods This was a prospective observational study that included 129 consecutive patients with non–small-cell lung cancer who received ICI monotherapy at a single center. Serial cardiac monitoring was performed during ICI monotherapy. Results A total of 35 (27%) patients developed any grade ≥1 CV–irAEs with a median time of onset of 72 (interquartile range 44-216) days after ICI treatment initiation. Multivariate Fine–Gray regression analysis showed that prior acute coronary syndrome (adjusted hazard ratio [HR] 3.15 (95% [CI], 2.03-4.91), prior heart failure hospitalization (adjusted HR 1.65 [95% CI, 1.17-2.33]), and achievement of disease control (adjusted HR 1.91, [95% CI, 1.16-3.14]) were significantly associated with grade ≥1 CV–irAEs. Serial cardiac monitoring revealed that patients with preceding grade 1 CV–irAEs were associated with a significantly higher risk of onset of grade ≥2 CV–irAEs compared with those without preceding grade 1 CV–irAEs (HR: 6.17 [95% CI, 2.97-12.83]). Conclusion CV–irAEs were more common than previously recognized and have several predictors. Moreover, serial cardiac monitoring may be feasible for the prediction of future grade ≥2 CV–irAEs.

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Section: Discussionmentioning

confidence: 99%

Incidence, Clinical Characteristics, and Predictors of Cardiovascular Immune-Related Adverse Events Associated with Immune Checkpoint Inhibitors

et al. 2022

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“…There is currently no consensus on the optimal immunosuppression treatment sequence, combination, and duration in steroid-refractory cases. Moreover, it should be taken into account that lymphocyte depletion associated with immunosuppressive therapy may induce the unleashing of aggressive melanoma and the progression of the disease [ 80 ]. A recent study showed that the blockade of TNFα may lead to preventing the manifestation of ICI-related cardiotoxicity [ 81 ].…”

Section: Review and Discussionmentioning

confidence: 99%

Myocarditis Induced by Immunotherapy in Metastatic Melanoma—Review of Literature and Current Guidelines

Czarnecka

Kleibert

Płachta

et al. 2022

JCM

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Immunotherapy is a widely used treatment modality in oncology. Immune checkpoint inhibitors, as a part of immunotherapy, caused a revolution in oncology, especially in melanoma therapy, due to the significant prolongation of patients’ overall survival. These drugs act by activation of inhibited immune responses of T lymphocytes against cancer cells. The mechanism responsible for the therapy’s high efficacy is also involved in immune tolerance of the patient’s own tissues. The administration of ICI therapy to a patient can cause severe immune reactions against non-neoplastic cells. Among them, cardiotoxicity seems most important due to the high mortality rate. In this article, we present the history of a 79 year-old patient diagnosed with melanoma who died due to myocarditis induced by ICI therapy, despite the fast administration of recommended immunosuppressive therapy, as an illustration of possible adverse events of ICI. Additionally, we summarize the mechanism, risk factors, biomarkers, and clinical data from currently published guidelines and studies about ICI-related myocarditis. The fast recognition of this fatal adverse effect of therapy may accelerate the rapid introduction of treatment and improve patients’ outcomes.

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“…Compared to echocardiography, assessment of LVEF by myocardial perfusion imaging is less susceptible to external factors [ 131 ]; compared to cardiac MR, the technique is advantageous in cost-effectiveness and patients who can or must not undergo MR imaging [ 131 ]. Therefore, myocardial perfusion imaging can potentially lead to early diagnosis and timely beginning of cardiac therapy and/or adjustment of immunotherapy, and several reports describe application of myocardial perfusion imaging in patients with immunotherapy-related cardiotoxicity [ 132 , 133 , 134 ]. As proposed, the technique was used for monitoring of cardiac function during immunotherapy treatment and for clarification of echocardiography results.…”

Section: Investigation Of Myocardial Perfusion and Viabilitymentioning

confidence: 99%

Shining Damaged Hearts: Immunotherapy-Related Cardiotoxicity in the Spotlight of Nuclear Cardiology

Kersting

Settelmeier

Mavroeidi

et al. 2022

IJMS

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The emerging use of immunotherapies in cancer treatment increases the risk of immunotherapy-related cardiotoxicity. In contrast to conventional chemotherapy, these novel therapies have expanded the forms and presentations of cardiovascular damage to a broad spectrum from asymptomatic changes to fulminant short- and long-term complications in terms of cardiomyopathy, arrythmia, and vascular disease. In cancer patients and, particularly, cancer patients undergoing (immune-)therapy, cardio-oncological monitoring is a complex interplay between pretherapeutic risk assessment, identification of impending cardiotoxicity, and post-therapeutic surveillance. For these purposes, the cardio-oncologist can revert to a broad spectrum of nuclear cardiological diagnostic workup. The most promising commonly used nuclear medicine imaging techniques in relation to immunotherapy will be discussed in this review article with a special focus on the continuous development of highly specific molecular markers and steadily improving methods of image generation. The review closes with an outlook on possible new developments of molecular imaging and advanced image evaluation techniques in this exciting and increasingly growing field of immunotherapy-related cardiotoxicity.

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Evolution of Immune Checkpoint Blockade–Induced Myocarditis Over 2 Years

Cited by 7 publications

References 8 publications

Incidence, Clinical Characteristics, and Predictors of Cardiovascular Immune-Related Adverse Events Associated with Immune Checkpoint Inhibitors

Incidence, Clinical Characteristics, and Predictors of Cardiovascular Immune-Related Adverse Events Associated with Immune Checkpoint Inhibitors

Myocarditis Induced by Immunotherapy in Metastatic Melanoma—Review of Literature and Current Guidelines

Shining Damaged Hearts: Immunotherapy-Related Cardiotoxicity in the Spotlight of Nuclear Cardiology

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