Biomarkers for Chemotherapy and Monoclonals Skin testing Stn ng fr och rn nig on HS Sloane JACI In Practice 2016 ‘Stn ostng (% poaive Wa 1011 60%) NA NA 27 (00%) 1 co0%) 97 (60%) 49 44%) 33 (00%) 27 (100%) (100%) (00%) Expensive Unavailable Unmet need: vials with 0.5m!co20%e Biomarkers for Monoclonals Spase Soa in Pertuzumab Anaphylaxis arate breast cancer who presented within 2-3 minutes of the secotd administration of pertunumab (approsimatey 32 mg in 20 mL) pruritus in palms and soles, sudden epigastric ain, ‘vomiting, dyspnea, wherzing, dizines, and presyneope. saturation decreased to 8496 and blood pressure to 70/40 mm Hg. Prompt zdminisration of 0.5 mL of inramucular 520K) Tryptase was not obtained atthe time o he reaction (ouside cancer instaton) “The phenotype ofthe reaction was Type !thely IgE-mediated cue to rmutiple exposures ‘A bags 12 steps desensitization protocol was generated and successfully ‘ppd or over 10 exposuresTyrosine Kinase Inhibitors Imatinib, the first commercial tyrosine kinase inhibitors (TKIs) into the clinical setting in 2000 to treat cancers; approximately fifteen other TKIs. Imatinib remains the most successful agent, whereas all the others have had modest effects on the cancers that they target. The current challenge is to identify the agents that need to be combined with TKIs to maximize their efficacy. One of the most promising approaches is to combine immune therapy with TKI treatment.Imatinib Hypersensitivity Itching and severe skin rash in a patient which was resistant to lowering the dose and corticosteroids no eosinophils in the biopsy change to next generation dasatinib was successful and the patient has continued on treatment indefinitely Albayrak et al EAJM 2011Desensitization For Monoclonal Antibodies, Check Point In| and Immune Modulators High risk procedure: requires the introduction of a potentially lethal medication to a highly sensitized patient Performed in critically ill patients: survival/quality of life depends on administration of a medication to which a patient has presented an adverse reaction No alternative medication is available or the alternatives (second and third line choices) have less demonstrated therapeutic value than It is a temporary phenomenon Antigen specific, not IgE depleting, not hapten inhibition nor depletion of mast cell mediators It is done by repetitive increasing sub-optimal doses (suboptimal concentrations) of the medication involved in the adverse reaction Once desensitization is complete, the tolerization can be maintained by continuous administration of the medicationConclusions es | All Immune Modulators, Check Point Inhibitors and Monoclonal Antibodies can induced immediate IgE/non IgE systemic reactions, delayed and locai reactions Skin testing predictive values depends on the type of reaction and the drug Desensitizations are available for immediate IgE/ non IgE reactions, delayed and local reactions but not for SCARS Research is needed to further understand the mechanisms of reactions, their management and treatment rs Y