A Case of Nivolumab-Induced Myositis

Fox, Eric A.; Dabrow, Michael; Ochsner, G

doi:10.1634/theoncologist.2016-0170

Cited by 28 publications

(6 citation statements)

References 6 publications

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“…15 Anti-PD-1 mAbs used to treat patients with various solid tumors, including thymoma, can trigger autoimmune complications such as myositis and myasthenia gravis. [16][17][18] The observation of myositis in the patient in this study is suggestive of the immunotherapeutic mechanism of action of spartalizumab.…”

Section: Discussionsupporting

confidence: 60%

Phase I study of the antiprogrammed cell death‐1 Ab spartalizumab (PDR001) in Japanese patients with advanced malignancies

et al. 2020

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Spartalizumab is a humanized IgG4/κ mAb directed against human programmed cell death‐1 (PD‐1). In this phase I study, we investigated safety, pharmacokinetics, preliminary antitumor activity, and toxicity of spartalizumab in patients with advanced malignancies. Patients (n = 18) with a range of tumor types received spartalizumab i.v. at doses of 1, 3, and 10 mg/kg every 2 weeks until disease progression, unacceptable toxicity, or discontinuation at the discretion of the investigator or patient. Most patients (61%) had received five or more prior lines of therapy. No dose‐limiting toxicities were reported and, hence, the maximum tolerated dose was 10 mg/kg or more. Pharmacokinetics in Japanese patients aligned with those reported in a global dose‐escalation study. The safety profile was consistent with other approved anti‐PD‐1 mAbs; the most common drug‐related adverse events were maculopapular rash (22%), followed by malaise and increased blood alkaline phosphatase (11% each). Partial responses were reported in two patients (11%), one with transitional cell carcinoma and the other with hepatocellular carcinoma. In conclusion, this study confirmed the safety of spartalizumab given at a dose of up to 10 mg/kg every 2 weeks in Japanese patients with cancers.

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Section: Discussionsupporting

confidence: 60%

Phase I study of the antiprogrammed cell death‐1 Ab spartalizumab (PDR001) in Japanese patients with advanced malignancies

et al. 2020

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“…Treatment with nivolumab has been associated with the development of myositis and myocarditis, even of the severe entity, in a number of case reports and case series, especially in Eastern Asia [ 21 - 25 ]. A patient treated with nivolumab for advanced colon cancer received a diagnosis of myasthenia gravis and myositis for bilateral ptosis, limb and neck weakness, dyspnea and myalgia developing in two weeks.…”

Section: Resultsmentioning

confidence: 99%

Musculoskeletal and Rheumatic Diseases Induced by Immune Checkpoint Inhibitors: A Review of the Literature

Benfaremo

Manfredi

Luchetti

et al. 2018

CDS

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Background: Immune checkpoint inhibitors are a new promising class of antitumor drugs that have been associated with a number of immune-related Adverse Events (AEs), including musculoskeletal and rheumatic disease.Methods: We searched Medline reviewing reports of musculoskeletal and rheumatic AEs induced by immune checkpoint inhibitors.Results: Several musculoskeletal and rheumatic AEs associated with immune checkpoint inhibitors treatment are reported in the literature. In particular, arthralgia and myalgia were the most common reported AEs, whereas the prevalence of arthritis, myositis and vasculitis is less characterized and mainly reported in case series and case reports. Other occasionally described AEs are sicca syndrome, polymyalgia rheumatica, systemic lupus erythematosus and sarcoidosis.Conclusion: Newly induced musculoskeletal and rheumatic diseases are a frequent adverse event associated with immune checkpoint inhibitors treatment

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“…An earlier report described heightened risk of immune-related myopathy with concurrent ICI and statin administration, even if prior statin use did not cause musculoskeletal symptoms [8]. History of prior statin myopathy was also reported in another case of ICI-associated myositis [9]. Other scenarios potentially supporting a "two-hit" hypothesis of irAE include markedly increased rates of pulmonary toxicity with combination anti-PD-L1 and epidermal growth factor receptor inhibition (up to 64% incidence, compared with ≤5% for either agent alone [10]) and heightened incidence of hepatic toxicity with combination anti-cytotoxic T lymphocyte antigen 4 and BRAF inhibition [11].…”

Section: Discussionmentioning

confidence: 90%

Statin Intolerance, Anti-HMGCR Antibodies, and Immune Checkpoint Inhibitor-Associated Myositis: A “Two-Hit” Autoimmune Toxicity or Clinical Predisposition?

et al. 2020

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Immune-related adverse events induced by immune checkpoint inhibitor (ICI) therapy may affect diverse organ systems, including skeletal and cardiac muscle. ICI-associated myositis may result in substantial morbidity and occasional mortality. We present a case of a patient with advanced non-small cell lung cancer who developed grade 4 myositis with concurrent myocarditis early after initiation of anti-programmed death ligand 1 therapy (durvalumab). Autoantibody analysis revealed marked increases in anti-3-hydroxy-3-methylglutaryl-coenzyme A reductase antibody levels that preceded clinical toxicity, and further increased during toxicity. Notably, the patient had a history of intolerable statin myopathy, which had resolved clinically after statin discontinuation and prior to ICI initiation. This case demonstrates a potential association between statin exposure, autoantibodies, and ICI-associated myositis. The Oncologist 2020;25:e1242-e1245

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A Case of Nivolumab-Induced Myositis

Abstract: Nivolumab (Opdivo) is a monoclonal antibody classified as an immune modulator. A case is presented of nivolumab-induced myositis, an unlisted side effect.

Cited by 28 publications

References 6 publications

Phase I study of the antiprogrammed cell death‐1 Ab spartalizumab (PDR001) in Japanese patients with advanced malignancies

Phase I study of the antiprogrammed cell death‐1 Ab spartalizumab (PDR001) in Japanese patients with advanced malignancies

Musculoskeletal and Rheumatic Diseases Induced by Immune Checkpoint Inhibitors: A Review of the Literature

Statin Intolerance, Anti-HMGCR Antibodies, and Immune Checkpoint Inhibitor-Associated Myositis: A “Two-Hit” Autoimmune Toxicity or Clinical Predisposition?

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