Diagnoses and Management of Drug Hypersensitivity and Anaphylaxis in Cancer and Chronic Inflammatory Diseases: Reactions to Taxanes and Monoclonal Antibodies

Abstract

Due to the increase in utilization of chemotherapies and antibodies, drug hypersensitivity reactions have increased dramatically worldwide, preventing the use of first-line therapies and impacting patients' survival and quality of life. Some of the more frequently used medications in cancer include taxanes for ovarian, lung, breast, and prostate cancers. Monoclonal antibodies are used in the treatment of neoplastic, autoimmune, and inflammatory diseases, and their clinical applications are becoming broader. Monoclonal antibody targets include CD20, HER-2, EGFR, IL-6 receptor, TNF-α, CD30, VEGF-A, IgE, and more, and examples of immunemediated and inflammatory diseases that respond to monoclonal antibodies include rheumatoid arthritis, Crohn's disease, ulcerative colitis, juvenile idiopathic arthritis, psoriasis and psoriatic arthritis, Wegener's granulomatosis, microscopic polyangiitis, ankylosing spondylitis, plaque psoriasis, and asthma. Neoplastic diseases include non-Hodgkin's lymphoma, chronic lymphocytic leukemia, and colorectal, breast, gastric, and lung cancer. The clinical presentation of drug hypersensitivity reactions ranges from mild cutaneous reactions to lifethreatening symptoms including anaphylaxis. Rapid drug desensitization (RDD) has become a groundbreaking approach to the management of immediate drug hypersensitivity reactions IgE and non-IgE mediated. It is the only effective procedure that enables sensitized patients to receive the full treatment dose safely, thus representing an important advance in the patients' treatment and prognosis. The aim of this review is to provide an update on hypersensitivity reactions to commonly used monoclonal and taxanes, their clinical presentations, diagnosis, and the use of RDD for their management.

Drug Hypersensitivity and Desensitizations: Mechanisms and New Approaches

“…Among the four most common HSRs described by Gell and Coombs, the most studied reactions are IgE (Immunoglobuline E)/mast cell mediated reactions which can cause cardiovascular collapse and anaphylaxis, leading to drug discontinuation which decrease quality of life and/or life expectancy [3,4,5,6]. …”

“…Other endotypes include direct complement activation [1,18], HSRs mediated by cyclooxygenase-1 inhibition in Aspirin Exacerbated Respiratory Disease (AERD) and Aspirin Exacerbated Cutaneous Disease (AECD) [19,20], or reactions due to some drugs with THIQ (tetrahydroisoquinoline)motifs which signal through the human G-protein-coupled receptor (MrgprX2) may also induce histamine release are included in the mast cell activation endotype [21,22]. In the past, symptoms such as fever, chills, and pain were not typically associated with allergic reactions, however, they have been reported during HSRs to monoclonals, oxaliplatin, and taxanes [3,6,9,23]. These type of reactions known as “cytokine storm-like reactions”, are mediated by the release of proinflammatory cytokines which activate macrophages and other immune cells with FcγR receptors [21].…”

“…Desensitization today is indicated when patients have HSRs mediated by mast cell activation to their first line therapy without comparable alternatives [3,4,5,26,30,38,39]. Desensitization is achieved by incrementally escalating the sub-optimal doses of the culprit drug until the required dose is reached, and DS induces a temporary tolerance which protects the patient from anaphylaxis [6,23,38].…”

“…Currently valid DS protocols have been established for other chronic diseases such as Cystic fibrosis, which has poor patient prognosis if antibiotic restrictions are present [5]. Recently these procedures have been developed for new and innovative drugs for oncologic and chronic inflammatory diseases which were continued first line therapies that were critical for patients’ quality of life and life expectancy [3,4]. Previously published data have shown that more than 20% of oncology patients who receive platin chemotherapy developed an allergic reaction.…”

“…Previously published data have shown that more than 20% of oncology patients who receive platin chemotherapy developed an allergic reaction. Equally concerning is the increasing number of unique monoclonal antibody (mAbs) therapies which have high rates of immunogenicity due to non-human mAb parts and glycosylation [3]. Preventing patients from using first line therapy can be taxing both in terms of cost but also in the reduction of quality of life, life expectancy, and disease progression or management.…”