Common Types of Hypersensitivity Reactions to Therapeutic Monoclonal Antibodies Mariana Castells M.D., Ph.D Drug Hypersensitivity and Desensitization Center Brigham and Women’s Hospital Dana-Farber Cancer Institute Harvard Medical School
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Common Types of Hypersensitivity
Reactions to Therapeutic Monoclonal
Antibodies
Mariana Castells M.D., Ph.DDrug Hypersensitivity and Desensitization Center
Brigham and Women’s Hospital
Dana-Farber Cancer Institute
Harvard Medical School
Emergency Use Authorizations (EUAs)
Emergency use authorizations (EUAs) for two monoclonal neutralizing antibodies (mAb) bamlanivimab and casirivimab/imdevimab to treat outpatients
with mild to moderate COVID-19 who are at high risk of progressing to severe disease.
Outpatients with mild or moderate symptoms, no more than 10 days of symptoms
Age ≥ 65, BMI ≥ 35
CKD, diabetes, immunosuppressed
Age ≥ 55 with cardiovascular disease, hypertension, COPD or other chronic respiratory conditions
Age 12-17 with variety of conditions (e.g., sickle cell, obesity)
Excluded if newly hypoxic or requiring more than baseline supplemental O2
Type I Acute
(IgE/Mast Cell/Basophil)
Type IV Delayed
(T cells, dendritic cells)TRYPTAS
E
Drug Hypersensitivity Reactions
Hypersenisitivity to pembrolizumab : sudden onset
itching , hives, sneezing, nasal congestion/rhinorrhea
and a lump in throat/upper palate, change in
voice along with periorbital/facial swelling.
Hypotension and desaturation requiring Epinephrine
Type I reactions (anaphylaxis): IgE antibodies binding to drug antigen and
cross-linkage of adjacent IgE molecules, leading to mediator release.
Type II (cytotoxic) reactions: IgG or IgM antibodies recognize drug antigen
associated with cell membranes, causing complement activation.
Type III (immune complex) reactions: formation of antigen-antibody
complexes.
Type IV (delayed hypersensitivity): mediated by sensitized lymphocytes.
G Gell and Coombs classification e
Few min to 60 min 1-24 hours 24h to 7/10 days 24 hours to 10 days
Hypersensitivity to Monoclonal Antibodies, Isabwe et al JACI 2018
Markers of anaphylaxis and cytokine release during reactions to Monoclonals Antibodies
39.2
13.9 14.6
6.3
56.2
5.5 50
10
20
30
40
50
60
Initial Reaction Before Desensitization After Desensitization
Tryptase
Level
Tryptase IgE-mediated HSR *
– 11.4 ng/mL or (2 + 1.2 × baseline level)
– Baseline ; 2-3 weeks after a reaction
IL-6 cytokine release
– Normal < 1.7 pg/mL
Mixed has elevated tryptase and IL-6
• Hereditary Alpha Tryptasemia
(Lyons et al Nature Genetics 2016 )
0
1000
2000
3000
4000
5000
Baseline Reactionseru
m I
L-6
(p
g/
mL
)
Serum IL-6 ChangeBaseline to Reaction
Grades of Reactions
Brown 2004
https://brightoncollaboration.us/
Mangement of Reactions To Monoclonal AntibodiesYang BC, Castells MC. Ann Allergy Asthma Immunol. 2019
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