Hypersensitivity to monoclonal antibodies used for cancer and inflammatory or connective tissue diseases

Abstract

Hypersensitivity reactions to therapeutic monoclonal antibodies for malignant tumors and inflammatory diseases can be classic type I (mast cell mediated, perhaps IgE dependent) reactions, cytokine release reactions, or type IV cell-mediated reactions.Classic allergic reactions to monoclonal antibodies, presumed to be mast cell mediated and possibly IgE dependent, can be treated with rapid drug desensitization. Rapid drug desensitization is effective and safe for carefully selected patients, allowing them to continue to receive first-line therapy.It is dubious whether rapid drug desensitization is effectively for cytokine release reactions to monoclonal antibodies, but such reactions can be effectively limited or prevented with appropriate premedications, intravenous fluids, and dose or frequency adjustment of the monoclonal antibody.Type IV cell-mediated reactions, such as erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis, drug reaction with eosinophilia and systemic symptoms, and other blistering reactions are absolute contraindications to reexposure to the implicated agent.

Hypersensitivity Reactions to Monoclonal Antibodies in Children

“…It is caused by large and rapid release of cytokines, such as interferon-gamma, TNF-alfa, IL-1 and IL-6, the latter identified as a possible biomarker of this type of reactions [33,88]. The cells releasing the responsible cytokines are not conclusively identified in all circumstances, but it is expected to involve CD8 + T cells, monocytes, natural killer cells and macrophages [89]. CRS quickly develops within minutes to a few hours following exposure and include specific symptoms (headache, low blood pressure, pain of the chest and back, fever, myalgia, arthralgia and rigors) and non-specific symptoms (rash, fatigue, dyspnea, throat tightness, dizziness/hypotension, vomiting, diarrhea) [35].…”

“…In mild cases, flu-like symptoms are present. In severe cases patients may develop aseptic meningitis, seizures, acute respiratory distress syndrome, renal failure, arrhythmia, cardiomyopathy, heart failure, hemophagocytic lymphohistiocytosis and macrophage activation syndrome [89]. CRSs appear on the first known administration and usually quickly disappear with repeated exposures [27].…”

“…No definitive data on the frequency of cross-reactivity between two mAbs are available so far. Cross-reactivity may be due to structural similarity of two BDs (i.e., specific glycosylation of the Fc portion of IgG1 framework) and to target specificity (some antigen binding by different mAbs) [89]. The aim of the graded challenge is not to reach tolerance but to confirm or rule out hypersensitivity.…”

Rituximab Hypersensitivity: From Clinical Presentation to Management

“…There's a general agreement about avoiding rituximab that has caused type IV HSR such as SJS, TEN, EM and DRESS as well as RISS (Hong and Sloane, 2019;Yang and Castells, 2019). For mild to moderate common infusion reactions to rituximab, the manufacturer's instructions are to reduce the rate of infusion and premedicate the patients with an antihistamine, acetaminophen and methylprednisolone prior to dosing and liaise the allergist if required (https://www.ema.europa.eu/en/ documents/product-information/mabthera-epar-product-information_en.pdf).…”

“…In the event of an HSR to rituximab such as Type 1, cytokine release, mixed reaction and delayed maculopapular rash, RDD is a safe and valid alternative. The management by multidisciplinary teams led by expert allergists and access to adequate facilities for allergy procedures has shown to be the optimal approach, with the best efficacy and safety results (Isabwe et al, 2018;Görgülü et al, 2019;Hong and Sloane, 2019).…”