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Modified protocol of omalizumab treatment to prevent carboplatin-induced drug hypersensitivity reactions: a case study

Modified protocol of omalizumab treatment to prevent carboplatin-induced drug hypersensitivity... Carboplatin administration can usually be safely continued via a so-called desensitisation protocol when hypersensi- tivity reactions arise. Severe break-through reactions that occur early during desensitisation are likely to be IgE-medi- ated; in that case, addition of omalizumab premedication should be strongly considered. Keywords: Carboplatin, Desensitisation, Drug hypersensitivity, Omalizumab Carboplatin treatment could, however, be successfully To the editor continued after pre-treatment with omalizumab and no Platinum-based chemotherapy is the cornerstone in the further adverse events occurred. treatment of various solid tumours, including gynaeco- The case concerns a now 57-year-old woman diagnosed logic malignancies. The incidence of drug hypersensitiv - with stage III ovarian cancer of the endometrioid type ity reactions (DHRs) is high; up to 12% for carboplatin in in 2008 (Table  1). In 2014, she had a platinum-sensitive gynaecological tumours [1]. The pathogenesis of platin- relapse without rational surgical options and palliative related DHRs may vary but for carboplatin, IgE-specific chemotherapy with carboplatin/paclitaxel was initiated. basophil activation has been demonstrated [2]. During the second cycle, she developed an allergic reac- Fortunately, patients with a DHR to carboplatin can tion consisting of patchy erythema, coughing, throat generally still be safely treated with carboplatin using a and chest discomfort. The chemotherapy was stopped desensitisation protocol [3]. Protocols rely on two main and referral to an allergologist followed. Carboplatin principles, namely gradually increasing the dose of drug hypersensitivity was diagnosed based on the clinical and using a premedication consisting of a combination presentation in combination with skin tests positive for of H1-, H2-antihistamines, corticosteroids and in some carboplatin (Table  2). Three subsequent cycles of carbo - cases a leukotriene antagonist [3]. This method is suc - platin were given according to a 10-step desensitisation cessful for most patients; however, some still suffer from schedule and were uneventful. (Figure 1a). symptoms despite intense pre-treatment and extra anti- The desensitisation procedure was successfully allergy medication during the desensitisation procedure. repeated with a relapse 3  years later. In 2018, carbopl- We describe a patient who developed a systemic aller- atin monotherapy was initiated due to a third sympto- gic reaction at the first step (1  mg carboplatin/hour) of matic platinum-sensitive relapse. During the first cycle, the desensitisation schedule on two separate occasions. an allergic reaction occurred at the last desensitisation step (Fig.  1b). The reaction consisted of flushing, pru - *Correspondence: a.a.j.m.van.de.ven@umcg.nl ritus and erythema of the face and chest. The carbopl - Department of Allergology and Internal Medicine, Internal address atin infused was stopped and intravenous clemastine code AA21, University Medical Center Groningen, Hanzeplein 1, 9713 GZ Groningen, The Netherlands was administered resulting in resolution of symptoms Full list of author information is available at the end of the article © The Author(s) 2020. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creat iveco mmons .org/licen ses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creat iveco mmons .org/publi cdoma in/ zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data. Oude Elberink et al. Clin Transl Allergy (2020) 10:5 Page 2 of 5 Table 1 Summary of clinical events and treatment over time Year Event Surgical debulking Adjuvant chemotherapy Allergology 2008 Stage III ovarian cancer of the endometri- Yes 6 Cycles of carboplatin and paclitaxel oid type 2010 Disease relapse Yes No 2013 Disease relapse Yes No 2014 Symptomatic platinum-sensitive disease Not possible 2 Cycles of carboplatin/paclitaxel Cycle 2: allergic reaction relapse Cycle 3 omitted Skin tests positive for carbopl- Cycle 4–6 according to 10-step desensiti- atin, negative for paclitaxel sation schedule 2017 Symptomatic platinum-sensitive disease No 6 Cycles of carboplatin/paclitaxel accord- Skin tests positive for carboplatin relapse ing to 10-step desensitisation schedule 2018 Symptomatic platinum-sensitive disease No 6 Cycles of carboplatin monotherapy Cycle 1: flushing, pruritus and relapse according to 10-step desensitisation erythema of the face and chest schedule with additional omalizumab Cycle 2 + 3: Anaphylaxis for cycle 4–6 Skin tests positive for carboplatin (negative for cisplatin) Cycle 4–6: Uneventful Skin tests persistently positive 2019 Symptomatic platinum-sensitive disease No 6 Cycles of carboplatin monotherapy No events relapse according to 10-step desensitisation schedule with additional omalizumab Table 2 Diagnostic testing in suspected carboplatin allergy Time after initial diagnosis (years) 6.5 9.5 11 11.2 Status Prior to 2nd series of Prior to 3rd series of After 3 cycles carboplatin After 6 cycles carboplatin carboplatin/pacli- carboplatin/pacli- monotherapy (4th series), 0x (4th series) and 4x omali- taxel taxel omalizumab zumab* Saline, diameter (mm) 0 0 0 0 Histamine, diameter (mm) 9.5 4 7.5 6 Drugs tested: diameter of wheal in mm Carboplatin 0.01 mg/ml 8.5 0 6 0 Carboplatin 0.1 mg/ml N/A 0 7 6.5 Carboplatin 1 mg/ml N/A 4.5 7.5 5.5 Paclitaxel 0.001 mg/ml 0 N/A N/A N/A Paclitaxel 0.01 mg/ml 0 N/A N/A N/A Paclitaxel 0.1 mg/ml 0 N/A N/A N/A Paclitaxel 1 mg/ml 0 N/A N/A N/A Cisplatin 0.01 mg/ml N/A N/A 0 0 Cisplatin 0.1 mg/ml N/A N/A 0 0 Cisplatin 1 mg/ml N/A N/A 0 0 Overview of intracutaneous testing for carboplatin and other chemotherapeutics. Positive results are shown in italics. Diameter = average of the length and width of the wheal, read 15–20 min after intracutaneous injection of the drug N/A not assessed * Skin tests were performed 8 weeks after the last omalizumab injection Oude Elberink et al. Clin Transl Allergy (2020) 10:5 Page 3 of 5 Total dose (mg) 726 C oncentra on (mg/ml) Total per solu on (mg) Solu on A 100 ml 0.5 50 Solu on B 100ml 0.726 72.6 Solu on C 150ml 4.84 726 Step Soluon Rate Time Administered Cumulave dose (ml/min) (min) dose (mg) (mg) 1 A 2 15 0.250 0.250 2 A 5 15 0.625 0.875 3 A 10 15 1.250 2.125 4 A 20 15 2.500 4.625 5 B 20 15 3.630 8.255 6 B 40 15 7.260 15.515 7 C 20 15 24.2 39.7 8 C 40 15 48.4 88.1 9 C 80 15 96.8 184.9 10 C 100 67 541.1 726.0 Fig. 1 Management of carboplatin allergy. a 10-step desensitisation schedule for carboplatin. Cumulative dose as administered in the 6th and last cycle of the course. b Overview of carboplatin and omalizumab administration in relation to the adverse allergic reactions within minutes. The desensitisation was successfully commencing the first infusion step, despite pre-treat - continued at the penultimate infusion rate. 3 weeks later ment with H1/H2-antihistamines and dexamethasone. she experienced a more severe reaction moments after She had symptoms of flushing, hypotension, dyspnoea Oude Elberink et al. Clin Transl Allergy (2020) 10:5 Page 4 of 5 with chest discomfort, throat tightness and abdominal Our results confirm their findings and suggest that one discomfort. Additional administration of clemastine, dose of omalizumab prior to the start of desensitisation ranitidine and dexamethasone had insufficient effect and may already be sufficient, thereby minimizing treat - 0.5  mg of intramuscular epinephrine was required to ment delay and enabling desensitisation procedures to relieve symptoms. There was no alternative explanation be kept at the regular time schedule of 3.5 h. for this reaction, i.e. no co-factors such as concurrent There is limited but growing experience using omali - infection, recent exercise or use of novel medications. zumab for desensitisation of DHR; case-reports or small After administration of the abovementioned medication, case series describe positive results for aspirin [5], insulin the desensitisation could be continued according to pro- [6], Elosulfase A, [7] and recently oxaliplatin [8]. Careful tocol without further additional medication or adverse selection of patients remains pivotal and sufficient knowl - events. During administration of the third cycle, despite edge regarding the underlying pathogenic mechanism of optimizing premedication (20  mg dexamethasone i.v., the allergic reaction is essential. Non-IgE-mediated reac- 50 mg ranitidine i.v., 2 mg clemastine i.v. and 10 mg mon- tions are less likely to fully respond to this therapy. Con- telukast orally, all ≥ 1 h prior to the first infusion), a simi - sequently, the mechanism of hypersensitivity reactions lar anaphylactic reaction occurred at the first infusion should ideally be substantiated by diagnostics in order to step. Intramuscular epinephrine halted the allergic reac- identify those patients that might benefit from the addi - tion and again, the desensitisation could be completed tion of omalizumab. Carboplatin-induced DHR are IgE- without other events. mediated, as specific anti-carboplatin IgE antibodies can Since further dilution of the carboplatin to allow an be detected in patients with DHR to carboplatin [9]. Iwa- even slower desensitisation was not possible (in accord- moto et  al. nicely demonstrated in  vitro an IgE-depend- ance to the SmPC of Carboplatin), other potential solu- ent mechanism in patients with carboplatin DHR [2]. tions were explored. Ojaimi et al. [4] described a patient The carboplatin reactivity was transferable when plasma who failed their 2-day and subsequently 4-day desen- of these patients was added to healthy control basophils, sitisation protocol for carboplatin. After 3 fortnightly but could be almost completely blocked when cells were doses of 300  mg of omalizumab, a monoclonal anti-IgE pre-treated with omalizumab. antibody, carboplatin was successfully administered over For our patient, measurement of anti-carboplatin 4 days. IgE was not available and a basophil activation test was We opted to aim to reduce the burden of anti-carbo- unsuccessful probably due to the presence of low lev- platin IgE-antibodies by administering omalizumab. els of omalizumab in the sample. Skin tests however Our patient received one dose of omalizumab 300  mg repeatedly showed reactivity to carboplatin, which sup- 2 weeks before the 4th cycle of carboplatin was adminis- ports the presence of an IgE-mediated DHR. tered, and continued fortnightly (Fig.  1b). The following Taken together, for patients with continued allergic three administrations of carboplatin occurred without reactions of established or strongly suspected IgE-medi- any side effects and no adaptations to the desensitisation ated origin despite a desensitisation schedule including protocol were required. Omalizumab was well tolerated. conventional anti-allergic medication, we recommend She had a good clinical and partial radiological response additional pre-treatment with one dose of omalizumab to the chemotherapy with 73% decreased CA-125 titres 1–3 weeks prior to each cycle of chemotherapy. and commenced maintenance treatment with niraparib In conclusion, omalizumab can be a valuable addi- 6  weeks after the last cycle of chemotherapy. Unfortu- tion to the allergologist’s repertoire for desensitisation nately, she relapsed within 6  months and carboplatin in case of patients suffering from adverse reactions sug - monotherapy was reinitiated. The anti-allergy premedi - gestive of an IgE-mediated allergy. cation regimen included omalizumab 300  mg every 14 days (first injection was given 11 days prior to the first Abbreviation cycle) and the desensitisation procedure was carried out DHR: drug hypersensitivity reaction. uneventfully. Acknowledgements We here describe the successful addition of omali- The authors would like to thank Annechien Lambeck and Laura Bungener for zumab to the conventional anti-allergic medication in a fruitful discussions and excellent laboratory assistance. patient with severe break-through allergic reactions to Authors’ contributions carboplatin despite an optimized desensitisation sched- MJ was the treating oncologist of the patient, HOE and AvdV managed ule. To our knowledge, this is the second time omali- and supervised the desensitisation procedure; HD was responsible for drug zumab has been used as an adjuvant during carboplatin delivery and (co-) developed the desensitisation schedule. HOE and AvdV wrote the article, AvdV drafted the figures, MJ and HD critically revised the desensitisation. Ojaimi and colleagues added omali- manuscript. All authors read and approved the final manuscript. zumab to a more conservative desensitisation protocol. Oude Elberink et al. Clin Transl Allergy (2020) 10:5 Page 5 of 5 Funding 2. Iwamoto T, Hirai H, Yamaguchi N, Kobayashi N, Sugimoto H, Tabata T, et al. No funding was provided specifically for this study. H.N.G. Oude Elberink’s Carboplatin-induced severe hypersensitivity reaction: role of IgE-depend- institution has received consultancy fees from ALK-Abelló. H.N.G. Oude ent basophil activation and FcepsilonRI. Cancer Sci. 2014;105(11):1472–9. Elberink has received fees for delivering lectures from Chiesi, ALK-Abelló and 3. Castells MC, Tennant NM, Sloane DE, Hsu FI, Barrett NA, Hong DI, Meda; has received consultancy fees from ALK-Abello; has received research et al. Hypersensitivity reactions to chemotherapy: outcomes and support from Novartis, MEDA Pharma, Mead Johnson, ALK-Abello, Shire, and safety of rapid desensitization in 413 cases. J Allergy Clin Immunol. Chiesi; and has received payment for developing educational presentations 2008;122(3):574–80. from ALK-Abello. M. Jalving’s institution has received consultancy fees from 4. Ojaimi S, Harnett PR, Fulcher DA. Successful carboplatin desensitization Merck, BMS, Novartis, PierreFabre, Tesaro, AstraZenica and fees for delivering by using omalizumab and paradoxical diminution of total IgE levels. J lectures from Sanofi. The other authors declare that they have no relevant Allergy Clin Immunol In Pract. 2014;2(1):105–6. conflicts of interest. 5. Lang DM, Aronica MA, Maierson ES, Wang XF, Vasas DC, Hazen SL. Omali- zumab can inhibit respiratory reaction during aspirin desensitization. Ann Availability of data and materials Allergy Asthma Immunol. 2018;121(1):98–104. The datasets used and analysed during the current study are available from 6. Yong PF, Malik R, Arif S, Peakman M, Amiel S, Ibrahim MA, et al. Rituximab the corresponding author on reasonable request. and omalizumab in severe, refractory insulin allergy. N Engl J Med. 2009;360(10):1045–7. Ethics approval and consent for publication 7. Arroabarren E, Aznal E, Anda M, Sanchez-Valverde F. Anaphylaxis after Informed consent for publication was provided by the patient. Elosulfase A infusion: omalizumab as coadyuvant for enzyme replace- ment therapy desensitization. Pediatr Allergy Immunol. 2019;31:491. Competing interests 8. Prieto-Garcia A, Noguerado B, Rojas P, Torrado I, Rodriguez-Fernandez A, The authors declare that they have no competing interests. Tornero P. Unexpected anaphylaxis after completing a desensitization protocol to oxaliplatin: successful adjuvant use of omalizumab. J Investig Author details Allergol Clin Immunol. 2019;29(1):53–5. Department of Allergology and Internal Medicine, Internal address code 9. Caiado J, Venemalm L, Pereira-Santos MC, Costa L, Barbosa MP, Castells M. AA21, University Medical Center Groningen, Hanzeplein 1, 9713 GZ Gronin- Carboplatin-, oxaliplatin-, and cisplatin-specific IgE: cross-reactivity and gen, The Netherlands. Department of Medical Oncology, University Medical value in the diagnosis of carboplatin and oxaliplatin allergy. J Allergy Clin Center Groningen, Groningen, The Netherlands. Department of Clinical Phar- Immunol Pract. 2013;1(5):494–500. macy and Pharmacology, University Medical Center Groningen, Groningen, The Netherlands. Publisher’s Note Springer Nature remains neutral with regard to jurisdictional claims in pub- Received: 30 September 2019 Accepted: 12 January 2020 lished maps and institutional affiliations. References 1. Markman M, Kennedy A, Webster K, Elson P, Peterson G, Kulp B, et al. Clinical features of hypersensitivity reactions to carboplatin. J Clin Oncol. 1999;17(4):1141. Ready to submit your research ? 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Modified protocol of omalizumab treatment to prevent carboplatin-induced drug hypersensitivity reactions: a case study

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Abstract

Carboplatin administration can usually be safely continued via a so-called desensitisation protocol when hypersensi- tivity reactions arise. Severe break-through reactions that occur early during desensitisation are likely to be IgE-medi- ated; in that case, addition of omalizumab premedication should be strongly considered. Keywords: Carboplatin, Desensitisation, Drug hypersensitivity, Omalizumab Carboplatin treatment could, however, be successfully To the editor continued after pre-treatment with omalizumab and no Platinum-based chemotherapy is the cornerstone in the further adverse events occurred. treatment of various solid tumours, including gynaeco- The case concerns a now 57-year-old woman diagnosed logic malignancies. The incidence of drug hypersensitiv - with stage III ovarian cancer of the endometrioid type ity reactions (DHRs) is high; up to 12% for carboplatin in in 2008 (Table  1). In 2014, she had a platinum-sensitive gynaecological tumours [1]. The pathogenesis of platin- relapse without rational surgical options and palliative related DHRs may vary but for carboplatin, IgE-specific chemotherapy with carboplatin/paclitaxel was initiated. basophil activation has been demonstrated [2]. During the second cycle, she developed an allergic reac- Fortunately, patients with a DHR to carboplatin can tion consisting of patchy erythema, coughing, throat generally still be safely treated with carboplatin using a and chest discomfort. The chemotherapy was stopped desensitisation protocol [3]. Protocols rely on two main and referral to an allergologist followed. Carboplatin principles, namely gradually increasing the dose of drug hypersensitivity was diagnosed based on the clinical and using a premedication consisting of a combination presentation in combination with skin tests positive for of H1-, H2-antihistamines, corticosteroids and in some carboplatin (Table  2). Three subsequent cycles of carbo - cases a leukotriene antagonist [3]. This method is suc - platin were given according to a 10-step desensitisation cessful for most patients; however, some still suffer from schedule and were uneventful. (Figure 1a). symptoms despite intense pre-treatment and extra anti- The desensitisation procedure was successfully allergy medication during the desensitisation procedure. repeated with a relapse 3  years later. In 2018, carbopl- We describe a patient who developed a systemic aller- atin monotherapy was initiated due to a third sympto- gic reaction at the first step (1  mg carboplatin/hour) of matic platinum-sensitive relapse. During the first cycle, the desensitisation schedule on two separate occasions. an allergic reaction occurred at the last desensitisation step (Fig.  1b). The reaction consisted of flushing, pru - *Correspondence: a.a.j.m.van.de.ven@umcg.nl ritus and erythema of the face and chest. The carbopl - Department of Allergology and Internal Medicine, Internal address atin infused was stopped and intravenous clemastine code AA21, University Medical Center Groningen, Hanzeplein 1, 9713 GZ Groningen, The Netherlands was administered resulting in resolution of symptoms Full list of author information is available at the end of the article © The Author(s) 2020. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creat iveco mmons .org/licen ses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creat iveco mmons .org/publi cdoma in/ zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data. Oude Elberink et al. Clin Transl Allergy (2020) 10:5 Page 2 of 5 Table 1 Summary of clinical events and treatment over time Year Event Surgical debulking Adjuvant chemotherapy Allergology 2008 Stage III ovarian cancer of the endometri- Yes 6 Cycles of carboplatin and paclitaxel oid type 2010 Disease relapse Yes No 2013 Disease relapse Yes No 2014 Symptomatic platinum-sensitive disease Not possible 2 Cycles of carboplatin/paclitaxel Cycle 2: allergic reaction relapse Cycle 3 omitted Skin tests positive for carbopl- Cycle 4–6 according to 10-step desensiti- atin, negative for paclitaxel sation schedule 2017 Symptomatic platinum-sensitive disease No 6 Cycles of carboplatin/paclitaxel accord- Skin tests positive for carboplatin relapse ing to 10-step desensitisation schedule 2018 Symptomatic platinum-sensitive disease No 6 Cycles of carboplatin monotherapy Cycle 1: flushing, pruritus and relapse according to 10-step desensitisation erythema of the face and chest schedule with additional omalizumab Cycle 2 + 3: Anaphylaxis for cycle 4–6 Skin tests positive for carboplatin (negative for cisplatin) Cycle 4–6: Uneventful Skin tests persistently positive 2019 Symptomatic platinum-sensitive disease No 6 Cycles of carboplatin monotherapy No events relapse according to 10-step desensitisation schedule with additional omalizumab Table 2 Diagnostic testing in suspected carboplatin allergy Time after initial diagnosis (years) 6.5 9.5 11 11.2 Status Prior to 2nd series of Prior to 3rd series of After 3 cycles carboplatin After 6 cycles carboplatin carboplatin/pacli- carboplatin/pacli- monotherapy (4th series), 0x (4th series) and 4x omali- taxel taxel omalizumab zumab* Saline, diameter (mm) 0 0 0 0 Histamine, diameter (mm) 9.5 4 7.5 6 Drugs tested: diameter of wheal in mm Carboplatin 0.01 mg/ml 8.5 0 6 0 Carboplatin 0.1 mg/ml N/A 0 7 6.5 Carboplatin 1 mg/ml N/A 4.5 7.5 5.5 Paclitaxel 0.001 mg/ml 0 N/A N/A N/A Paclitaxel 0.01 mg/ml 0 N/A N/A N/A Paclitaxel 0.1 mg/ml 0 N/A N/A N/A Paclitaxel 1 mg/ml 0 N/A N/A N/A Cisplatin 0.01 mg/ml N/A N/A 0 0 Cisplatin 0.1 mg/ml N/A N/A 0 0 Cisplatin 1 mg/ml N/A N/A 0 0 Overview of intracutaneous testing for carboplatin and other chemotherapeutics. Positive results are shown in italics. Diameter = average of the length and width of the wheal, read 15–20 min after intracutaneous injection of the drug N/A not assessed * Skin tests were performed 8 weeks after the last omalizumab injection Oude Elberink et al. Clin Transl Allergy (2020) 10:5 Page 3 of 5 Total dose (mg) 726 C oncentra on (mg/ml) Total per solu on (mg) Solu on A 100 ml 0.5 50 Solu on B 100ml 0.726 72.6 Solu on C 150ml 4.84 726 Step Soluon Rate Time Administered Cumulave dose (ml/min) (min) dose (mg) (mg) 1 A 2 15 0.250 0.250 2 A 5 15 0.625 0.875 3 A 10 15 1.250 2.125 4 A 20 15 2.500 4.625 5 B 20 15 3.630 8.255 6 B 40 15 7.260 15.515 7 C 20 15 24.2 39.7 8 C 40 15 48.4 88.1 9 C 80 15 96.8 184.9 10 C 100 67 541.1 726.0 Fig. 1 Management of carboplatin allergy. a 10-step desensitisation schedule for carboplatin. Cumulative dose as administered in the 6th and last cycle of the course. b Overview of carboplatin and omalizumab administration in relation to the adverse allergic reactions within minutes. The desensitisation was successfully commencing the first infusion step, despite pre-treat - continued at the penultimate infusion rate. 3 weeks later ment with H1/H2-antihistamines and dexamethasone. she experienced a more severe reaction moments after She had symptoms of flushing, hypotension, dyspnoea Oude Elberink et al. Clin Transl Allergy (2020) 10:5 Page 4 of 5 with chest discomfort, throat tightness and abdominal Our results confirm their findings and suggest that one discomfort. Additional administration of clemastine, dose of omalizumab prior to the start of desensitisation ranitidine and dexamethasone had insufficient effect and may already be sufficient, thereby minimizing treat - 0.5  mg of intramuscular epinephrine was required to ment delay and enabling desensitisation procedures to relieve symptoms. There was no alternative explanation be kept at the regular time schedule of 3.5 h. for this reaction, i.e. no co-factors such as concurrent There is limited but growing experience using omali - infection, recent exercise or use of novel medications. zumab for desensitisation of DHR; case-reports or small After administration of the abovementioned medication, case series describe positive results for aspirin [5], insulin the desensitisation could be continued according to pro- [6], Elosulfase A, [7] and recently oxaliplatin [8]. Careful tocol without further additional medication or adverse selection of patients remains pivotal and sufficient knowl - events. During administration of the third cycle, despite edge regarding the underlying pathogenic mechanism of optimizing premedication (20  mg dexamethasone i.v., the allergic reaction is essential. Non-IgE-mediated reac- 50 mg ranitidine i.v., 2 mg clemastine i.v. and 10 mg mon- tions are less likely to fully respond to this therapy. Con- telukast orally, all ≥ 1 h prior to the first infusion), a simi - sequently, the mechanism of hypersensitivity reactions lar anaphylactic reaction occurred at the first infusion should ideally be substantiated by diagnostics in order to step. Intramuscular epinephrine halted the allergic reac- identify those patients that might benefit from the addi - tion and again, the desensitisation could be completed tion of omalizumab. Carboplatin-induced DHR are IgE- without other events. mediated, as specific anti-carboplatin IgE antibodies can Since further dilution of the carboplatin to allow an be detected in patients with DHR to carboplatin [9]. Iwa- even slower desensitisation was not possible (in accord- moto et  al. nicely demonstrated in  vitro an IgE-depend- ance to the SmPC of Carboplatin), other potential solu- ent mechanism in patients with carboplatin DHR [2]. tions were explored. Ojaimi et al. [4] described a patient The carboplatin reactivity was transferable when plasma who failed their 2-day and subsequently 4-day desen- of these patients was added to healthy control basophils, sitisation protocol for carboplatin. After 3 fortnightly but could be almost completely blocked when cells were doses of 300  mg of omalizumab, a monoclonal anti-IgE pre-treated with omalizumab. antibody, carboplatin was successfully administered over For our patient, measurement of anti-carboplatin 4 days. IgE was not available and a basophil activation test was We opted to aim to reduce the burden of anti-carbo- unsuccessful probably due to the presence of low lev- platin IgE-antibodies by administering omalizumab. els of omalizumab in the sample. Skin tests however Our patient received one dose of omalizumab 300  mg repeatedly showed reactivity to carboplatin, which sup- 2 weeks before the 4th cycle of carboplatin was adminis- ports the presence of an IgE-mediated DHR. tered, and continued fortnightly (Fig.  1b). The following Taken together, for patients with continued allergic three administrations of carboplatin occurred without reactions of established or strongly suspected IgE-medi- any side effects and no adaptations to the desensitisation ated origin despite a desensitisation schedule including protocol were required. Omalizumab was well tolerated. conventional anti-allergic medication, we recommend She had a good clinical and partial radiological response additional pre-treatment with one dose of omalizumab to the chemotherapy with 73% decreased CA-125 titres 1–3 weeks prior to each cycle of chemotherapy. and commenced maintenance treatment with niraparib In conclusion, omalizumab can be a valuable addi- 6  weeks after the last cycle of chemotherapy. Unfortu- tion to the allergologist’s repertoire for desensitisation nately, she relapsed within 6  months and carboplatin in case of patients suffering from adverse reactions sug - monotherapy was reinitiated. The anti-allergy premedi - gestive of an IgE-mediated allergy. cation regimen included omalizumab 300  mg every 14 days (first injection was given 11 days prior to the first Abbreviation cycle) and the desensitisation procedure was carried out DHR: drug hypersensitivity reaction. uneventfully. Acknowledgements We here describe the successful addition of omali- The authors would like to thank Annechien Lambeck and Laura Bungener for zumab to the conventional anti-allergic medication in a fruitful discussions and excellent laboratory assistance. patient with severe break-through allergic reactions to Authors’ contributions carboplatin despite an optimized desensitisation sched- MJ was the treating oncologist of the patient, HOE and AvdV managed ule. To our knowledge, this is the second time omali- and supervised the desensitisation procedure; HD was responsible for drug zumab has been used as an adjuvant during carboplatin delivery and (co-) developed the desensitisation schedule. HOE and AvdV wrote the article, AvdV drafted the figures, MJ and HD critically revised the desensitisation. Ojaimi and colleagues added omali- manuscript. All authors read and approved the final manuscript. zumab to a more conservative desensitisation protocol. Oude Elberink et al. Clin Transl Allergy (2020) 10:5 Page 5 of 5 Funding 2. Iwamoto T, Hirai H, Yamaguchi N, Kobayashi N, Sugimoto H, Tabata T, et al. No funding was provided specifically for this study. H.N.G. Oude Elberink’s Carboplatin-induced severe hypersensitivity reaction: role of IgE-depend- institution has received consultancy fees from ALK-Abelló. H.N.G. Oude ent basophil activation and FcepsilonRI. Cancer Sci. 2014;105(11):1472–9. Elberink has received fees for delivering lectures from Chiesi, ALK-Abelló and 3. Castells MC, Tennant NM, Sloane DE, Hsu FI, Barrett NA, Hong DI, Meda; has received consultancy fees from ALK-Abello; has received research et al. Hypersensitivity reactions to chemotherapy: outcomes and support from Novartis, MEDA Pharma, Mead Johnson, ALK-Abello, Shire, and safety of rapid desensitization in 413 cases. J Allergy Clin Immunol. Chiesi; and has received payment for developing educational presentations 2008;122(3):574–80. from ALK-Abello. M. Jalving’s institution has received consultancy fees from 4. Ojaimi S, Harnett PR, Fulcher DA. Successful carboplatin desensitization Merck, BMS, Novartis, PierreFabre, Tesaro, AstraZenica and fees for delivering by using omalizumab and paradoxical diminution of total IgE levels. J lectures from Sanofi. The other authors declare that they have no relevant Allergy Clin Immunol In Pract. 2014;2(1):105–6. conflicts of interest. 5. Lang DM, Aronica MA, Maierson ES, Wang XF, Vasas DC, Hazen SL. Omali- zumab can inhibit respiratory reaction during aspirin desensitization. Ann Availability of data and materials Allergy Asthma Immunol. 2018;121(1):98–104. The datasets used and analysed during the current study are available from 6. Yong PF, Malik R, Arif S, Peakman M, Amiel S, Ibrahim MA, et al. Rituximab the corresponding author on reasonable request. and omalizumab in severe, refractory insulin allergy. N Engl J Med. 2009;360(10):1045–7. Ethics approval and consent for publication 7. Arroabarren E, Aznal E, Anda M, Sanchez-Valverde F. Anaphylaxis after Informed consent for publication was provided by the patient. Elosulfase A infusion: omalizumab as coadyuvant for enzyme replace- ment therapy desensitization. Pediatr Allergy Immunol. 2019;31:491. Competing interests 8. Prieto-Garcia A, Noguerado B, Rojas P, Torrado I, Rodriguez-Fernandez A, The authors declare that they have no competing interests. Tornero P. Unexpected anaphylaxis after completing a desensitization protocol to oxaliplatin: successful adjuvant use of omalizumab. J Investig Author details Allergol Clin Immunol. 2019;29(1):53–5. Department of Allergology and Internal Medicine, Internal address code 9. Caiado J, Venemalm L, Pereira-Santos MC, Costa L, Barbosa MP, Castells M. AA21, University Medical Center Groningen, Hanzeplein 1, 9713 GZ Gronin- Carboplatin-, oxaliplatin-, and cisplatin-specific IgE: cross-reactivity and gen, The Netherlands. Department of Medical Oncology, University Medical value in the diagnosis of carboplatin and oxaliplatin allergy. J Allergy Clin Center Groningen, Groningen, The Netherlands. Department of Clinical Phar- Immunol Pract. 2013;1(5):494–500. macy and Pharmacology, University Medical Center Groningen, Groningen, The Netherlands. Publisher’s Note Springer Nature remains neutral with regard to jurisdictional claims in pub- Received: 30 September 2019 Accepted: 12 January 2020 lished maps and institutional affiliations. References 1. Markman M, Kennedy A, Webster K, Elson P, Peterson G, Kulp B, et al. Clinical features of hypersensitivity reactions to carboplatin. J Clin Oncol. 1999;17(4):1141. Ready to submit your research ? 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Journal

Clinical and Translational Allergy – Springer Journals

Published: Jan 29, 2020

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