Chemotherapy induced Hypersensitivity reactions

Chemotherapy-induced Hypersensitivity reactionsA look at whats causing them and what to do when they happenEoin Tabb MPSI 18/4/2016

DefinitionsHypersensitivity Reaction: An over-expressed immune response that results in tissue harm or changes throughout the body in response to an antigen or foreign substance.Anaphylaxis reaction: An acute inflammatory reaction which results from the release of histamine from mast cells, causing a hypersensitivity immune response. Can cause SOB, light-headedness, hypotension, loss of consciousness and can lead to death.Cytokine-release syndrome: Caused by the release of cytokines. Can cause nausea, headache, tachycardia, hypotension, rash and SOB. IT ONLY OCCURS WITH MONOCLONAL ANTIBODIES

Allergy vs. side effectMost side effects in chemotherapy are predictable such as hair loss, mucositis, nephrotoxicity, hepatotoxicity, ototoxicity, immunosuppression etc. are caused by the chemotherapy affecting the non-cancerous normal cells in the body.Hypersensitivity reactions are not common, are unpredictable, and is unrelated to the known pharmacologic reactions of the chemotherapeutic agent.

ImmunologyTypeMechanismSigns and SymptomsIAnaphylactic: Immediate immunoglobulin E (IgE) mediated reactionFever, nausea, vomiting, flushing, back pain, angioedema, rash, dyspnea, bronchospasm, feelings of impending doom, circulatory collapseIICytotoxic: Antigen-antibody complexes activate inflammatory pathwaysHemolysisIIISerum Sickness: Immune complexes form and deposit in various tissuesVasculitis, nephritis, arthritisIVDelayed Cytotoxic: Activated T-Cells destroy targeted cellsGraft rejection, contact dermatitis, granuloma formation, Graft-Vs-Host Disease

Acute hypersensitivity reactions are mostly IgE mediated

IgE Mechanism of Action

Antigen is presented from the hypersensitivity reaction causing substance to the immune system.The antigen is processed by antigen presenting cells And are then presented to T-Helper Cells. T Helper Cells produce cytokines which stimulate B cells to proliferate and differentiate into IgE producing plasma cells. IgE attach by their constant regions to mast cells to receptors on mast cells. Mast cells contain chemicals which induce a hypersensitivity response. Once attached IgE molecules can last for several weeks.On second exposure of an antigen, the antigen attaches to the IgE antibodies on the mast cells. Within seconds of exposure, the mast cells release a cytokines and other mediators of the inflammatory response system causing a variety of symptoms.

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Key Offenders:Monoclonal AntibodiesMonoclonal antibodies may lead to rare, non-allergic, cytokine mediated hypersensitivity reactions within the first hours after infusion.Unlike, type 1 mediated reactions, symptoms appear to subside with each subsequent dose.Reactions of cytokine release may be managed through short-term cessation of drug infusion, administration of H1 antagonists and restarting the infusion at a slower rate.

H1 antagonist examples: Diphenhydramine, Chlorphenamine6

Key Offenders:Monoclonal AntibodiesDrugTargetType of ABIncidence of Severe HSR (%)Specific SymptomsSPC Pre-medsRechallengeRituximabCD20Chimeric