Hypersensitivity reactions to chemotherapy: Outcomes and safety of rapid desensitization in 413 cases - 15/08/11

Doi : 10.1016/j.jaci.2008.02.044

Mariana C. Castells, MD, PhD ^a,^⁎^{^{These authors contributed equally to this work.}} , Nichole M. Tennant, BA ^a,^{^{These authors contributed equally to this work.}}, David E. Sloane, MD ^a,^{^{These authors contributed equally to this work.}}, F. Ida Hsu, MD ^a,^{^{These authors contributed equally to this work.}}, Nora A. Barrett, MD ^a, David I. Hong, MD ^a, Tanya M. Laidlaw, MD ^a, Henry J. Legere, MD ^a, Samridhi N. Nallamshetty, MD ^a, Ross I. Palis, MD ^a, Jayanti J. Rao, MD ^a, Suzanne T. Berlin, DO ^b, Susana M. Campos, MD ^b, Ursula A. Matulonis, MD ^b
^a Department of Medicine, Division of Rheumatology, Immunology, and Allergy, Brigham and Women’s Hospital, Boston, Mass
^b Department of Medical Oncology, Dana Farber Cancer Institute, Boston, Mass

Reprint requests: Mariana C. Castells, MD, PhD, One Jimmy Fund Way, Smith Building, Room 626D, Boston, MA 02115.

Abstract

Background

Hypersensitivity reactions (HSRs) to chemotherapeutic drugs, including mAbs, often require that the provoking medication be discontinued, thus raising a dilemma for the caregiver: further use could precipitate a severe, even fatal, allergic reaction on re-exposure, but alternative drugs might be poorly tolerated or much less effective compared with the preferred agent.

Objective

We have developed a standardized rapid desensitization protocol for achieving temporary tolerization to drug allergens. In this study we evaluate the safety and efficacy of this protocol.

Methods

Ninety-eight patients who had HSRs in response to treatment with carboplatin, cisplatin, oxaliplatin, paclitaxel, liposomal doxorubicin, doxorubicin, or rituximab received rapid desensitization to these agents. A standardized 12-step protocol was used, with treatment given intravenously or intraperitoneally. Initial desensitizations occurred in the medical intensive care unit, whereas most subsequent infusions took place in an outpatient setting. Safety and efficacy of the protocol were assessed by review of treatment records.

Results

Of the 413 desensitizations performed, 94% induced mild or no reactions. No life-threatening HSRs or deaths occurred during the procedure, and all patients received their full target dose. Most reactions occurred during the first desensitization. Reactions were most commonly reported at the last step of the protocol. Desensitizations through the intravenous and intraperitoneal routes were equally effective.

Conclusions

Our standardized 12-step protocol for rapid drug desensitization is safe and effective and has been adopted as the standard of care at our institutions in treating patients with HSRs to chemotherapeutic drugs, including mAbs.

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Key words : Anaphylaxis, chemotherapy agents, monoclonal antibodies, rapid desensitization, hypersensitivity reactions, carboplatin, paclitaxel, adverse drug reactions

Abbreviations used : BWH, DFCI, HSR, MICU

Plan

Methods

Patients

Initial reaction classification

Skin test for hypersensitivity

Twelve-step rapid desensitization protocol

Treatment of reactions during desensitization

Results

Patient characteristics

Characteristics of initial HSRs

Skin test results

Rapid desensitization experience

Reactions during desensitizations

Discussion

Supported by the Ovations for the Cure Desensitization Program.

Disclosure of potential conflict of interest: D. E. Sloane has received honoraria from Genentech. F. I. Hsu has served as a coinvestigator for Dyax Corporation and has received a research grant from the American Academy of Allergy, Asthma & Immunology. N. A. Barrett has served as a coinvestigator for the National Institutes of Health and has served as a primary investigator for the American Academy of Allergy, Asthma & Immunology and Altana. D. I. Hong and T. M. Laidlaw have received training grant salary from the National Institutes of Health. S. N. Nallamshetty has received training grant salary from the National Institutes of Health and research grants from the American Academy of Allergy, Asthma & Immunology and GlaxoSmithKline. S. M. Campos has served as a research consultant for Genentech and has received research support from Genentech, Novartis, and Ortho-Biotechnology. The rest of the authors have declared that they have no conflict of interest.