Immune Checkpoint Inhibitor-Related Myositis: From Biology to Bedside

Solimando, Antonio Giovanni; Crudele, Lucilla; Leone, Patrizia; Argentiero, Antonella; Guarascio, Matteo; Silvestris, Nicola; Racanelli, Vito

doi:10.3390/ijms21093054

Cited by 49 publications

(44 citation statements)

References 69 publications

(100 reference statements)

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“…Based on these findings, we propose a flowchart to detect neurological irAEs as early as possible during routine clinical treatment. Neurological complications potentially related to ICI therapy vary from myositis [ 17 , 18 ] and MG [ [19] , [20] , [21] ]to inflammatory demyelinating polyneuropathies [ [22] , [23] , [24] , [25] ] to granulomatous inflammation of the CNS [ 21 ], multifocal CNS demyelination [ 26 ], meningitis [ 22 ], myelitis [ 19 ] and encephalopathy [ 13 ]. In particular, when ICI is implemented by non-neurological professionals, neurotoxicity can be difficult to diagnose and may therefore be underreported.…”

Section: Discussionmentioning

confidence: 99%

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Detect it so you can treat it: A case series and proposed checklist to detect neurotoxicity in checkpoint therapy

et al. 2021

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Background Checkpoint inhibitors show impressive and durable responses in various cancer types and provide new avenues for cancer immunotherapy. However, these drugs have a variety of adverse events. Common autoimmune-related adverse effects include fatigue, hepatitis, skin rash, endocrine deficiencies, and colitis. Neurotoxicity has been reported, but its incidence and course remain unclear. Methods To illustrate the broad spectrum of neurotoxicity, we exemplarily report the neurological adverse events of five patients with melanoma and one patient with differentiated thyroid cancer who received checkpoint inhibitors at Essen University Hospital (Essen, Germany). Results After treatment with ipilimumab, nivolumab or pembrolizumab, neurotoxic effects included hypophysitis-associated neck pain and headache, Guillain-Barré syndrome, transverse myelitis, acute brachial plexus neuritis, and ocular myasthenia gravis. Conclusions Checkpoint inhibitor therapy remains a success story; however, neurological immune-related adverse events may cause severe life-threatening conditions. We propose a guide for the early detection of neurological adverse events during routine clinical treatment to prevent more severe courses of checkpoint inhibitor-induced neurotoxicity.

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Section: Discussionmentioning

confidence: 99%

“…In particular, when ICI is implemented by non-neurological professionals, neurotoxicity can be difficult to diagnose and may therefore be underreported. The data on incidence of irAE is very limited [ 18 ].…”

Section: Discussionmentioning

confidence: 99%

Detect it so you can treat it: A case series and proposed checklist to detect neurotoxicity in checkpoint therapy

et al. 2021

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“…Since the first Food and Drug Administration (FDA) and European Medicines Agency (EMA) approval of the immune checkpoint inhibitor (ICI) ipilimumab for melanoma, which targets the anti CTLA-4 checkpoint, an explosion of approval of different ICIs that target a PD1 or programmed death-ligand 1 (PDL1) for a wide range of cancer indications has been observed [ 45 , 46 ]. The ICIs have provided significant clinical benefit including improvement in overall survival for some of the most aggressive and often lethal cancers [ 47 ]; however, despite the promising results, the overall objective response rate gained by ICIs as a monotherapy remains suboptimal, ranging between 20 to 30%, and overall survival and toxicity profile still need to be improved [ 48 , 49 , 50 ]. One strategy applied to accomplish higher clinical response is to generate more effective antitumor shrinkage by combining multiple checkpoints [ 51 ].…”

Section: Improving Immune–vascular Crosstalk For Cancer Immunothermentioning

confidence: 99%

“…One strategy applied to accomplish higher clinical response is to generate more effective antitumor shrinkage by combining multiple checkpoints [ 51 ]. Nonetheless, the toxicity profile is higher [ 49 , 52 ]. Therefore, there is a growing interest aimed to identify alternative strategies to improve the clinical outcome and antitumor response of ICIs, without significantly increasing the risk of toxicities.…”

Section: Improving Immune–vascular Crosstalk For Cancer Immunothermentioning

confidence: 99%

Cancer-Associated Angiogenesis: The Endothelial Cell as a Checkpoint for Immunological Patrolling

Solimando

Summa

Vacca

et al. 2020

Cancers

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Cancer-associated neo vessels’ formation acts as a gatekeeper that orchestrates the entrance and egress of patrolling immune cells within the tumor milieu. This is achieved, in part, via the directed chemokines’ expression and cell adhesion molecules on the endothelial cell surface that attract and retain circulating leukocytes. The crosstalk between adaptive immune cells and the cancer endothelium is thus essential for tumor immune surveillance and the success of immune-based therapies that harness immune cells to kill tumor cells. This review will focus on the biology of the endothelium and will explore the vascular-specific molecular mediators that control the recruitment, retention, and trafficking of immune cells that are essential for effective antitumor immunity. The literature revision will also explore how abnormalities in the tumor endothelium impair crosstalk with adaptive immune cells and how targeting these abnormalities can improve the success of immune-based therapies for different malignancies, with a particular focus on the paradigmatic example represented by multiple myeloma. We also generated and provide two original bio-informatic analyses, in order to sketch the physiopathology underlying the endothelial–neoplastic interactions in an easier manner, feeding into a vicious cycle propagating disease progression and highlighting novel pathways that might be exploited therapeutically.

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“…It was difficult to increase the dose of corticosteroids in this case because of severe steroid-induced cataracts, as well as oral candidiasis. We considered administering immunosuppressive agents; however, because of renal dysfunction and the risk of opportunistic infections due to immunosuppression, we proceeded with intravenous immunoglobulin (IVIg) therapy instead of immunosuppressants [ 3 ]. If that did not work, we planned to use a combination of immunosuppressive agents.…”

Section: Case Reportmentioning

confidence: 99%

A Rare Case of Pembrolizumab-Induced Dermatomyositis in a Patient with Cancer of Unknown Primary Origin

et al. 2021

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Patient: Female, 71-year-old Final Diagnosis: Dermatomyositis Symptoms: Fever • walking difficulties Medication: — Clinical Procedure: Corticosteroids Specialty: Immunology • Oncology • Rheumatology Objective: Rare disease Background: Pembrolizumab is a humanized monoclonal antibody against programmed cell death-1 protein. Pembrolizumab sometimes causes immune-related adverse events (irAEs). Dermatomyositis is a rare irAE of immune checkpoint inhibitors. The presentation is usually acute, and symptoms include edema with erythema of the eyelids, erythema of the forehead, and muscle weakness in both thighs. Case Report: Here we report a case of pembrolizumab-induced dermatomyositis in a 71-year-old Japanese woman with cancer of unknown primary origin, who experienced a high fever and had difficulty walking after her sixth course of pembrolizumab. General physical examination revealed edema with a heliotrope rash, V-neck signs, and non-specific erythema of the forehead. Laboratory evaluation revealed that myogenic enzymes were within normal ranges. Autoantibody tests revealed that antinuclear antibodies were negative, and autoantibodies related to myositis and anti-acetylcholine receptor antibodies were also negative. A magnetic resonance imaging scan of the thighs revealed signal abnormalities in the left lateral and distal vastus medialis muscle. The patient was treated with corticosteroids, subsequently followed by intravenous immunoglobulin therapy, which led to an improvement of the symptoms. Conclusions: Pembrolizumab-induced dermatomyositis is rare. Corticosteroids have been administered in many cases, and this case also suggests the efficacy of intravenous immunoglobulin therapy in treating immune checkpoint inhibitor-related dermatomyositis. This case highlights practical management of pembrolizumab-induced dermatomyositis.

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Immune Checkpoint Inhibitor-Related Myositis: From Biology to Bedside

Cited by 49 publications

References 69 publications

Detect it so you can treat it: A case series and proposed checklist to detect neurotoxicity in checkpoint therapy

Detect it so you can treat it: A case series and proposed checklist to detect neurotoxicity in checkpoint therapy

Cancer-Associated Angiogenesis: The Endothelial Cell as a Checkpoint for Immunological Patrolling

A Rare Case of Pembrolizumab-Induced Dermatomyositis in a Patient with Cancer of Unknown Primary Origin

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