Background: Rapid drug desensitization (RDD) induces a temporary tolerance to biologics which induce hypersensitivity reactions (HSRs). Data are limited regarding the use of RDD outside the USA. Our purpose was to report our data on RDD to rituximab, infliximab, cetuximab, and trastuzumab. Methods: The study was conducted as a retrospective chart review of patients with symptoms of HSRs to biologics. HSRs were classified as grades I, II, and III, based on their severity. Skin-prick tests/intradermal tests (IDTs) were performed with the implicated biologics. The 12-step RDD protocol was used. Results: The study group comprised 11 women and 6 men (mean age: 47 ± 11.7 years). Fourteen patients experienced HSRs to rituximab; 3 had HSRs to cetuximab, infliximab, and trastuzumab, respectively. HSRs to cetuximab, infliximab, and trastuzumab occurred during the first infusion and were all grade III. Twelve of the 14 patients with rituximab hypersensitivity had a reaction during the first infusion; 10 patients had grade II reactions and 4 had grade III reactions. Respiratory symptoms were the most frequent presentation of HSR. Skin tests with rituximab were performed on 10 patients; only 3 resulted in positive IDTs (with 1:100 dilutions) and the other tests were negative as were those performed with the other biologics. Of 96 RDDs, 89 desensitizations were performed with rituximab, 5 with cetuximab, 1 with infliximab, and 1 with trastuzumab. There were 12 (13.5%) breakthrough reactions, all of which were associated with rituximab and were less severe than the initial reactions. Conclusion: RDD was found to be safe and effective in the largest case series of RDDs with biologics in our country, Turkey.

1.
Cheifetz A, Smedley M, Martin S, Reiter M, Leone G, Mayer L, et al: The incidence and management of infusion reactions to infliximab: a large center experience. Am J Gastroenterol 2003;98:1315-1324.
2.
Chung KY, Shia J, Kemeny NE, Shah M, Schwartz GK, Tse A, et al: Cetuximab shows activity in colorectal cancer patients with tumors that do not express the epidermal growth factor receptor by immunohistochemistry. J Clin Oncol 2005;23:1803-1810.
3.
Cook-Bruns N: Retrospective analysis of the safety of Herceptin immunotherapy in metastatic breast cancer. Oncology 2001;61(suppl 2):58-66.
4.
Makris MP, Papadavid E, Zuberbier T: The use of biologicals in cutaneous allergies - present and future. Curr Opin Allergy Clin Immunol 2014;14:409-416.
5.
Castells M: Drug desensitization in oncology: chemotherapy agents and monoclonal antibodies; in Pichler WJ (ed): Drug Hypersensitivity. Basel, Karger, 2007, pp 413-425.
6.
Brennan PJ, Rodriguez Bouza T, Hsu FI, Sloane DE, Castells MC: Hypersensitivity reactions to mAbs: 105 desensitizations in 23 patients, from evaluation to treatment. J Allergy Clin Immunol 2009;124:1259-1266.
7.
del Carmen Sancho M, Breslow R, Sloane D, Castells M: Desensitization for hypersensitivity reactions to medications. Chem Immunol Allergy 2012;97:217-233.
8.
Syrigou E, Dannos I, Kotteas E, Makrilia N, Tourkantonis I, Dilana K, et al: Hypersensitivity reactions to docetaxel: retrospective evaluation and development of desensitization protocol. Int Arch Allergy Immunol 2011;156:320-324.
9.
Cernadas JR, Brockow K, Romano A, Aberer W, Torres MJ, Bircher A, Campi P, Sanz ML, Castells M, Demoly P, Pichler WJ; European Network of Drug Allergy and the EAACI interest group on drug hypersensitivity. General considerations on rapid desensitization for drug hypersensitivity - a consensus statement. Allergy 2010;65:1357-1366.
10.
Brown SG: Clinical features and severity grading of anaphylaxis. J Allergy Clin Immunol 2004;114:371-376.
11.
Brockow K, Garvey LH, Aberer W, Atanaskovic-Markovic M, Barbaud A, et al: Skin test concentrations for systemically administered drugs - an ENDA/EAACI Drug Allergy Interest Group position paper. Allergy 2013;68:702-712.
12.
Hong DI, Bankova L, Cahill KN, Kyin T, Castells MC: Allergy to monoclonal antibodies: cutting-edge desensitization methods for cutting-edge therapies. Expert Rev Clin Immunol 2012;8:43-52; quiz 3-4.
13.
Castells MC, Tennant NM, Sloane DE, Hsu FI, Barrett NA, Hong DI, et al: Hypersensitivity reactions to chemotherapy: outcomes and safety of rapid desensitization in 413 cases. J Allergy Clin Immunol 2008;122:574-580.
14.
Galvao VR, Castells MC: Hypersensitivity to biological agents-updated diagnosis, management, and treatment. J Allergy Clin Immunol Pract 2015;3:175-185.
15.
Breslow RG, Caiado J, Castells MC: Acetylsalicylic acid and montelukast block mast cell mediator-related symptoms during rapid desensitization. Ann Allergy Asthma Immunol 2009;102:155-160.
16.
Madrigal-Burgaleta R, Berges-Gimeno MP, Angel-Pereira D, Ferreiro-Monteagudo R, Guillen-Ponce C, et al: Hypersensitivity and desensitization to antineoplastic agents: outcomes of 189 procedures with a new short protocol and novel diagnostic tools assessment. Allergy 2013;68:853-861.
17.
Scherer K, Brockow K, Aberer W, Gooi JH, Demoly P, Romano A, Schnyder B, Whitaker P, Cernadas JS, Bircher AJ; European Network on Drug Allergy: Desensitization in delayed drug hypersensitivity reactions - an EAACI position paper of the Drug Allergy Interest Group. Allergy 2013;68:844-852.
18.
Ataca P, Atilla E, Kendir R, Bavbek S, Ozcan M: Successful desensitization of a patient with rituximab hypersensitivity. Case Reports Immunol 2015;2015:524507.
19.
Abadoglu O, Epozturk K, Atayik E, Kaptanoglu E: Successful rapid rituximab desensitization for hypersensitivity reactions to monoclonal antibodies in a patient with rheumatoid arthritis: a remarkable option. J Invest Allergol Clin Immunol 2010;21:319-321.
20.
Lebel E, Ben-Yehuda D, Bohbot E, Dranitzki Z, Shalit M, Tal Y: Hypersensitivity reactions to rituximab: 53 successful desensitizations in patients with severe, near-fatal reactions. J Allergy Clin Immunol Pract 2016;4:1000-1002.
21.
Vultaggio A, Matucci A, Nencini F, Pratesi S, Petroni G, Cammelli D, et al: Drug-specific Th2 cells and IgE antibodies in a patient with anaphylaxis to rituximab. Int Arch Allergy Immunol 2012;159:321-326.
22.
Vultaggio A, Matucci A, Nencini F, Pratesi S, Parronchi P, Rossi O, Romagnani S, Maggi E: Anti-infliximab IgE and non-IgE antibodies and induction of infusion-related severe anaphylactic reactions. Allergy 2010;65:657-661.
23.
Amoros-Reboredo P, Sanchez-Lopez J, Bastida-Fernandez C, do Pazo-Oubina F, Borras-Maixenchs N, Gine E, et al: Desensitization to rituximab in a multidisciplinary setting. Int J Clin Pharm 2015;37:744-748.
24.
O'Neil BH, Allen R, Spigel DR, Stinchcombe TE, Moore DT, Berlin JD, et al: High incidence of cetuximab-related infusion reactions in Tennessee and North Carolina and the association with atopic history. J Clin Oncol 2007;25:3644-3648.
25.
Chung CH, Mirakhur B, Chan E, Le Q-T, Berlin J, Morse M, et al: Cetuximab-induced anaphylaxis and IgE specific for galactose-α-1,3-galactose. N Engl J Med 2008;358:1109-1117.
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.