Prevention of allergic reactions during oxaliplatin desensitization through inhibition of Bruton tyrosine kinase

Kristin A Erickson; James E Norton; Jennifer Law; Nicole Soriano; Malgorzata Strojny; Nicole Gentry; Morgan Fried; Bruce S Bochner; Sheetal Kircher; Whitney W Stevens

doi:10.1016/j.jaci.2024.03.010

Prevention of allergic reactions during oxaliplatin desensitization through inhibition of Bruton tyrosine kinase

J Allergy Clin Immunol. 2024 Mar 21:S0091-6749(24)00294-X. doi: 10.1016/j.jaci.2024.03.010. Online ahead of print.

Affiliations

¹ Division of Allergy and Immunology, Northwestern Medicine, Chicago, Ill.
² Department of Pharmacy, Northwestern Medicine, Chicago, Ill.
³ Division of Hematology and Oncology, Northwestern University Feinberg School of Medicine, Chicago, Ill.
⁴ Division of Allergy and Immunology, Northwestern Medicine, Chicago, Ill. Electronic address: whitney-stevens@northwestern.edu.

PMID: 38521096
DOI: 10.1016/j.jaci.2024.03.010

Abstract

Background: Acute infusion reactions to oxaliplatin, a chemotherapeutic used to treat gastrointestinal cancers, are observed in about 20% of patients. Rapid drug desensitization (RDD) protocols often allow the continuation of oxaliplatin in patients with no alternative options. Breakthrough symptoms, including anaphylaxis, can still occur during RDD.

Objective: Our aim was to evaluate whether pretreatment with acalabrutinib, a Bruton tyrosine kinase inhibitor, can prevent anaphylaxis during RDD in a patient sensitized to oxaliplatin.

Methods: A 52-year-old male with locally advanced gastric carcinoma developed anaphylaxis during his fifth cycle of oxaliplatin. As he required 6 additional cycles to complete his curative-intent treatment regimen, he underwent RDD to oxaliplatin but still developed severe acute reactions. The risks and benefits of adding acalabrutinib before and during RDD were reviewed, and the patient elected to proceed.

Results: With acalabrutinib taken before and during the RDD, the patient was able to tolerate oxaliplatin RDD without complication. Consistent with its mechanism of action, acalabrutinib completely blocked the patient's positive skin prick response to oxaliplatin. Acalabrutinib did not alter the percentage of circulating basophils (1.24% vs 0.98%) before the RDD but did protect against basopenia (0.74% vs 0.09%) after the RDD. Acalabrutinib was associated with a drastic reduction in the ability of basophils to upregulate CD63 in vitro following incubation with oxaliplatin (0.11% vs 2.38%) or polyclonal anti-human IgE antibody (0.08% vs 44.2%).

Conclusions: Five doses of acalabrutinib, 100 mg, orally twice daily starting during the evening 2 days before and continuing through RDD allowed a sensitized patient to receive oxaliplatin successfully and safely.

Keywords: Acalabrutinib; Bruton tyrosine kinase inhibitor; acute hypersensitivity reaction; anaphylaxis; basophil; chemotherapy; drug allergy; infusion reaction; oxaliplatin; rapid drug desensitization.