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Open AccessJournal ArticleDOI

Pembrolizumab Therapy Triggering an Exacerbation of Preexisting Autoimmune Disease: A Report of 2 Patient Cases.

TLDR
Whether this autoimmune activation is associated with a clinical response to therapy has been debated, and while not definitive, there is evidence in the literature of a possible association.
Abstract
Historically, metastatic melanoma was uniformly and rapidly lethal, and treatment options were limited. In recent years, however, checkpoint inhibitors have emerged as an accepted standard treatment for patients with advanced melanoma. In clinical trials, these agents have been largely well tolerated and have the potential to result in durable responses. Importantly though, one must recognize the unique side effect profile of these therapies, which can trigger or exacerbate underlying autoimmune disease. Whether this autoimmune activation is associated with a clinical response to therapy has been debated, and while not definitive, there is evidence in the literature of a possible association. The 2 cases presented describe this autoimmune phenomenon, along with a review of the existing literature on the relationship between response to immunotherapy and autoimmune side effects.

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Use of immune checkpoint inhibitors in the treatment of patients with cancer and preexisting autoimmune disease: A systematic review

TL;DR: A systematic review of all reported cases describing the use of CPIs in patients with cancer and preexisting autoimmune disease to summarize the evidence on adverse events associated with CPI therapy provides a synthesis of current evidence to aid in clinical decision making and planning of future studies in this population.
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Myasthenia gravis: An emerging toxicity of immune checkpoint inhibitors.

TL;DR: A new case of pembrolizumab-induced MG is presented and insights are provided into the underlying mechanisms of action of this phenomenon, which emphasises the importance of early recognition and robust treatment of this toxicity.
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Neurological toxicities associated with immune-checkpoint inhibitors.

TL;DR: ICI-associated irAEs constitute a new group of neurologic complications of systemic anticancer therapies, although potentially severe, these rare neurologic toxicities are often responsive to immune-modulating therapies.
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Neuromuscular adverse events associated with anti-PD-1 monoclonal antibodies: Systematic review.

TL;DR: Mortality was high in patients treated with nivolumab or pembrolizumab monotherapy or concurrent with other immunologic agents, such as ipilimumab, despite adequate treatment strategies including corticosteroid, IV immunoglobulins, and plasma exchange.
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Clinical features, predictive correlates, and pathophysiology of immune-related adverse events in immune checkpoint inhibitor treatments in cancer: a short review.

TL;DR: The possibility that two distinct pathways may be contributing to the phenomenon of irAEs within this class of drugs is explored, and the role that this might play in future research and clinical practice is explored.
References
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Journal ArticleDOI

Immune Checkpoint Blockade in Cancer Therapy

TL;DR: Concluding remarks are made that principles learned during the development of CTLA-4 and PD-1/PD-L1 approaches will likely be used as new immunologic checkpoint blocking antibodies begin clinical investigation, and whether they enhance the efficacy of either approach alone is investigated.
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Mechanism-driven biomarkers to guide immune checkpoint blockade in cancer therapy

TL;DR: This work discusses biomarkers for anti-PD1 therapy based on immunological, genetic and virological criteria and suggests mechanism-based insights from such studies may guide the design of synergistic treatment combinations based on immune checkpoint blockade.
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High-Dose Recombinant Interleukin 2 Therapy for Patients With Metastatic Melanoma: Analysis of 270 Patients Treated Between 1985 and 1993

TL;DR: High-dose IL-2 treatment seems to benefit some patients with metastatic melanoma by producing durable CRs or PRs and should be considered for appropriately selected melanoma patients.
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Treatment of 283 Consecutive Patients With Metastatic Melanoma or Renal Cell Cancer Using High-Dose Bolus Interleukin 2

TL;DR: Because IL-2 does not have a direct effect on cancer cells but rather mediates its antitumor activity by altering host immune reactions, these data represent the best available evidence that immunologic therapy for cancer can be effective in selected patients.
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