Concomitant myasthenia gravis, myositis, myocarditis and polyneuropathy, induced by immune-checkpoint inhibitors: A life–threatening continuum of neuromuscular and cardiac toxicity

Background:The introduction of Immune Checkpoint Inhibitors in the recent years has resulted in high response rates and extended survival in patients with metastatic/advanced malignancies. Their mechanism of action is the indirect activation of cytotoxic T-cells through the blockade of inhibitory receptors of immunomodulatory pathways, such as cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4), programmed cell death protein-1 (PD-1) and its ligand (PD-L1). Despite their impressive therapeutic results, they can also induce immune-related toxicity, affecting various organs, including the skin.Objective:To provide an updated summarized overview of the most common immune-mediated cutaneous side effects and their management.Method:English articles derived from the databases PubMed and SCOPUS and published between 2009 and 2018, were analyzed for this narrative review.Results:The most common adverse cutaneous reactions include maculopapular rash, lichenoid reactions, vitiligo and pruritus, with severity Grade 1 or 2. Less frequent but eventually life-threatening skin side effects, including Stevens-Johnson syndrome, Drug Reaction with Eosinophilia and Systemic Symptoms and Toxic Epidermal necrolysis, have also been reported.Conclusion:Basic knowledge of the Immune-Checkpoint-Inhibitors-induced skin toxicity is necessary in order to recognize these treatment-related complications. The most frequent skin side effects, such as maculopapular rash, vitiligo and pruritus, tend to subside under symptomatic treatment so that permanent discontinuation of therapy is not commonly necessary. In the case of life-threatening side effects, apart from the necessary symptomatic treatment, the immunotherapy should be permanently stopped. Information concerning the management of ICIs-mediated skin toxicity can be obtained from the literature as well as from the Summary of Product Characteristics of each agent.

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How can we manage the cardiac toxicity of immune checkpoint inhibitors?

Expert Opinion on Drug Safety ◽

10.1080/14740338.2021.1906860 ◽

2021 ◽

Author(s):

Remo Poto ◽

Giancarlo Marone ◽

Flora Pirozzi ◽

Maria Rosaria Galdiero ◽

Alessandra Cuomo ◽

...

Keyword(s):

Immune Checkpoint ◽

Immune Checkpoint Inhibitors ◽

Cardiac Toxicity ◽

Checkpoint Inhibitors

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Cardiac toxicity of immune-checkpoint inhibitors: a clinical case of nivolumab-induced myocarditis and review of the evidence and new challenges

Cancer Management and Research ◽

10.2147/cmar.s185202 ◽

2019 ◽

Vol Volume 11 ◽

pp. 4541-4548 ◽

Cited By ~ 9

Author(s):

Roberto Martin Huertas ◽

Cristina Saavedra Serrano ◽

Cristian Perna ◽

Ana Ferrer Gómez ◽

Teresa Alonso Gordoa

Keyword(s):

Immune Checkpoint ◽

Immune Checkpoint Inhibitors ◽

Clinical Case ◽

Cardiac Toxicity ◽

Checkpoint Inhibitors ◽

New Challenges

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Management of pulmonary toxicity associated with immune checkpoint inhibitors

European Respiratory Review ◽

10.1183/16000617.0012-2019 ◽

2019 ◽

Vol 28 (154) ◽

pp. 190012 ◽

Cited By ~ 14

Author(s):

Myriam Delaunay ◽

Grégoire Prévot ◽

Samia Collot ◽

Laurent Guilleminault ◽

Alain Didier ◽

...

Keyword(s):

Adverse Events ◽

Immune Checkpoint ◽

Pulmonary Toxicity ◽

Immune Checkpoint Inhibitors ◽

Cytotoxic T Lymphocyte ◽

Checkpoint Inhibitors ◽

Standard Of Care ◽

Serious Adverse Events ◽

Programmed Cell Death 1 ◽

Life Threatening

Immunotherapy has become a standard of care in oncology, following the recent approvals of cytotoxic T-lymphocyte-associated protein-4 and programmed cell death-1 inhibitors in lung cancer, melanoma, renal cell carcinoma, Hodgkin's lymphoma, bladder, head and neck cancers. Besides their efficacy, these agents also generate specific immune-related adverse events. Due to the increasing prescription of immune-checkpoint inhibitors, the incidence of immune toxicity will continue to rise. The awareness of immune-related adverse events is key to ensuring both diagnosis and management of the possible serious adverse events. Although severe immune-related adverse events remain rare, they can lead to discontinued treatment or to death if they are not forecasted and managed properly. Even if lung toxicity is not the most frequent adverse event, it remains critical as it can be life-threatening. Herein, the main aspects of pulmonary toxicity are reviewed and guidelines are also proposed in order to manage the possible side-effects.

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Metastatic Merkel cell carcinoma and myasthenia gravis: contraindication for therapy with immune checkpoint inhibitors?

Journal for ImmunoTherapy of Cancer ◽

10.1186/s40425-019-0626-9 ◽

2019 ◽

Vol 7 (1) ◽

Cited By ~ 4

Author(s):

Anne Zaremba ◽

Eleftheria Chorti ◽

Finja Jockenhöfer ◽

Saskia Bolz ◽

Selma Sirin ◽

...

Keyword(s):

Myasthenia Gravis ◽

Cell Carcinoma ◽

Merkel Cell Carcinoma ◽

Immune Checkpoint ◽

Immune Checkpoint Inhibitors ◽

Checkpoint Inhibitors ◽

Merkel Cell

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Case Report: Cardiac Toxicity Associated With Immune Checkpoint Inhibitors

Frontiers in Cardiovascular Medicine ◽

10.3389/fcvm.2021.727445 ◽

2021 ◽

Vol 8 ◽

Author(s):

Ru Chen ◽

Ling Peng ◽

Zhihua Qiu ◽

Yan Wang ◽

Fen Wei ◽

...

Keyword(s):

Immune Checkpoint ◽

Immune Checkpoint Inhibitors ◽

Troponin I ◽

Systemic Corticosteroid ◽

Checkpoint Inhibitors ◽

Cardiac Conduction ◽

Fulminant Myocarditis ◽

Cancer Type ◽

Life Threatening ◽

The Subject

Immune checkpoint inhibitors (ICIs) have now emerged as a mainstay of treatment for various cancer. Along with the development of ICIs, immune-related adverse effects (irAEs) have been the subject of wide attention. The cardiac irAE, a rare but potentially fatal and fulminant effect, have been reported recently. This article retrospectively reviewed 10 cases from our hospital with cardiac irAEs, with severity ranging from asymptomatic troponin-I elevations to cardiac conduction abnormalities and even fulminant myocarditis. In our series, all the cases were solid tumors and lung cancer was the most frequent cancer type (4,40%). In total, three (30.0%) patients experienced more than one type of life-threatening complication. A systemic corticosteroid was given to nine patients (90.0%). The majority of cases (7, 70%) were performed at an initial dose of 1–2 mg/kg/day. Two (20.0%) patients were admitted to ICU, three (30.0%) patients were put on mechanical ventilation, two (20.0%) patients received the plasma exchange therapy, and one patient was implanted with a pacemaker. Two (20.0%) of the patients succumbed and died, with a median duration of 7.5 days (IQR5.0–10.0) from diagnosis of cardiac irAE to death. Based on these results, we recommend that clinicians be alert to cardiac irAEs, including performing cardiovascular examinations before ICI treatment to accurately diagnose suspected myocarditis, enabling immediate initiation of immunosuppressive therapy to improve prognosis.

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