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

Abstract

BackgroundAcute 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. Break-through symptoms including anaphylaxis can still occur during RDDs. ObjectiveTo evaluate if pretreatment with acalabrutinib, a Bruton’s tyrosine kinase inhibitor, can prevent anaphylaxis during a RDD in a patient sensitized to oxaliplatin. MethodsA 52-year-old male with locally advanced gastric carcinoma developed anaphylaxis during his 5th 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 prior to and during a RDD, were reviewed and he elected to proceed. ResultsWith acalabrutinib taken prior to and during the RDD, the patient was able to tolerate oxaliplatin RDDs 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% versus 0.98%) prior to the RDD but protected from basopenia (0.74% versus 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% versus 2.38%) or polyclonal anti-human IgE antibody (0.08% versus 44.2%). ConclusionsFive doses of acalabrutinib 100mg orally twice daily starting the evening 2 days before and continuing through a RDD allowed a sensitized patient to successfully and safely receive oxaliplatin.