Table 3. Hypersensitivity/adverse reactions of monoclonal antibodies used for cancer therapy.

mAbsa	Hypersensitivityb/adversec reactions		Refs
	Systemic	Cutaneous
Catumaxomabd	SIRS; abdominal disorders; CRS; pyrexia; cytopeniase; hepatotoxicity; dyspnoea; infections; immunogenicity	Rash; erythema; hyperhidrosis; pruritus; allergic dermatitis	34 , 35
Ibritumomab tiuxetan	IR; infections; severe cytopenias; immunogenicity; secondary malignancies	EM; SJS; TEN; bullous dermatitis; exfoliative dermatitis	36
Tositumomab-I131	Anaphylaxis; severe cytopenias; IR; fetal harm; hypothyroidism; secondary malignancies; infection; immunization	In clinical trial: Skin reactions, all grades - rash 17%, pruritus 10%, sweating 8%. Grades 3 and 4 - 0 - < 1%; exfol. dermatitis	37 , 38
Brentuximab vedotin	PN; IR; cytopenias; TLS; immunogenicity; PML; fetal harm; anaphylaxis	SJS; rash; pruritus; alopecia	39 , 40
Cetuximab	IR; cardiopulmonary arrest; pulmonary toxicity; electrolyte imbalance; GI; infection	Acneiform rash; nail changes; pruritus; xeroderma; paronychial inflammation	18 , 41 – 44
Rituximab	IR; TLS; PML; renal toxicity; infections; cardiac events; pulmonary events; bowel obstruct. and perforation; neutropenia; RA; anaphylaxis; HBR; SS	Paraneoplastic pemphigus; lichenoid dermatitis; vesiculobullous dermatitis; SJS; TEN	18 , 44 – 50
Alemtuzumabf	IR; cytopenias; infections,g immunogenicity; cardiac events; pulmonary events	Urticaria; rash; erythema; pruritus	44 , 51 – 53
Bevacizumab	GI perforation; hemorrhage; wound healing complications; thrombosis; IR; hypertension; necrotizing fasciitis; proteinurea; pulmonary events	Exfoliative dermatitis; alopecia	44 , 53 – 57
Pertuzumab	Embryo-fetal toxicity; IR; cytopenias; GI; PN; hypersensitivity/anaphylaxis; LVD	Alopecia; rash; paronychia; pruritus	58 , 59
Trastuzumab	Cardiomyopathyh; embryo-fetal toxicity; IR; LVD; pulmonary eventsi; neutropeniaj; anaphylaxis/angioedema; anemia; GI	Rash; nail disorders; pruritus	18 , 44 , 60 , 61
Trastuzumab Emtansinek	Hepatotoxicity; LVD; fetal harm; pulmonary events; thrombocytopenia; neurotoxicity; hypersensitivity/IR	Rash; pruritus	62
Denosumab	Hypocalcemia; embryo-fetal toxicity; ONJ and osteomyelitis; fatigue/asthenia; dyspnea	Dermatitis; eczema; rash; pruritus	63
Ipilimumab	IMR; diarrhea; fatigue	Dermatitis; pruritus; rashl	64 – 66
Ofatumumab	IR; cytopenias; intestinal obstruction; PML; HBR; pneumonia; pyrexia; infections; cough; dyspnea; diarrhea; fatigue	Rash; urticaria; hyperhidrosis	67 , 68
Panitumumabm,o	IR; pulm. Fibrosisn; pulmonary embolism, electrolyte depletion; GI; fatigue	Rash; dermatitis 'acneiform'; exfoliation; erythema; pruritus; xerosis; paronychia; skin fissures; photosensitivityo	18 , 69

^a Approved by FDA and/or European Medicines Agency (EMA). ^bReactions known or suspected of having an immunological basis. ^cOther adverse reactions with no clearly established, or yet to be demonstrated, immune mechanism (eg.nausea, cough, diarrhea, fatigue, sweating etc). ^dRegistered by EMA, Health Canada and Ministry of Health, Israel but not FDA. ^eMeans one or more of anemia, lymphopenia, neutropenia, thrombocytopenia. ^fWithdrawn from US and Europe in 2012 to be re-launched for MS. ^gIn particular, Pneumocystis jiroveci, CMV, EBV, herpes virus. ^hLeft ventricular dysfunction. Greatest risk when administered with anthracyclines. ⁱInterstitial pneumonitis, dyspnea, ARDS, pulmonary infiltrates/fibrosis/edema, pleural effusions. ^jHighest with myelosuppressive therapy. ^kCalled Ado-trastuzumab emtansine in the US ^lSJS/TEN, Sweet's syndrome, DRESS seen rarely. ^mNot indicated for use in combination with chemotherapy due to increased toxicity. ⁿShould be discontinued in patients developing interstitial lung disease, pneumonitis, lung infiltrates. ^oMost common adverse reactions are skin toxicities. CRS, cytokine release syndrome; EM, erytheme multiforme; GI, gastrointestinal symptoms, e.g., nausea, diarrhea, vomiting, constipation etc; HBR, hepatitis B reactivation; IMR, immune-mediated reactions due to T cell activation and proliferation – enterocolitis, hepatitis, dermatitis, neuropathies, endocrinopathies; IR, infusion reactions; LVD, left ventricular dysfunction; ONJ, osteonecrosis of the jaw; PML, progressive multifocal leukoencephalopathy; PN, peripheral neuropathy; RA, rheumatoid arthritis; SIRS, systemic inflammatory response syndrome; SJS, Stevens-Johnson syndrome; SS, serum sickness-like reactions; TEN, toxic epidermal necrolysis;, TLS, tumor lysis syndrome;