Immune-Related Adverse Events Associated with Immune Checkpoint Blockade 

The new england journal o f medicine

158 n engl j med 378;2 nejm.org January 11, 2018

Review Article

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Immunotherapy
enhances a patient’s immune system to fight disease
and has recently been a source of promising new cancer treatments.
Among the many immunotherapeutic strategies, immune checkpoint blockade
has shown remarkable benefit in the treatment of a range of cancer types. Immune
checkpoint blockade increases antitumor immunity by blocking intrinsic downregulators
of immunity, such as cytotoxic T-lymphocyte antigen 4 (CTLA-4) and
programmed cell death 1 (PD-1) or its ligand, programmed cell death ligand 1
(PD-L1). Several immune checkpoint–directed antibodies have increased overall
survival for patients with various cancers and are approved by the Food and Drug
Administration (Table 1).

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By increasing the activity of the immune system, immune checkpoint blockade
can have inflammatory side effects, which are often termed immune-related adverse
events. Although any organ system can be affected, immune-related adverse
events most commonly involve the gastrointestinal tract, endocrine glands, skin,
and liver.1
Less often, the central nervous system and cardiovascular, pulmonary,
musculoskeletal, and hematologic systems are involved. The wide range of potential
immune-related adverse events requires multidisciplinary, collaborative management
by providers across the clinical spectrum (Fig. 1).
No prospective trials have defined strategies for effectively managing specific
immune-related adverse events; thus, clinical practice remains variable. Nevertheless,
several professional organizations are working to harmonize expert consensus
on managing specific immune-related adverse events. In this review, we focus
on 10 essential questions practitioners will encounter while caring for the expanding
population of patients with cancer who are being treated with immune checkpoint
blockade (Table 2).orologi replica

Why Do Immune-Related Adverse Events Occur?

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