Desensitization to imatinib in patients with leukemia

Abstract

Imatinib mesylate is a tyrosine kinase inhibitor used for the treatment of chronic myeloid leukemia and hypereosinophilic syndrome. Imatinib is associated with a variety of adverse cutaneous reactions, including urticaria, maculopapular exanthem, generalized exanthematous pustulosis, exfoliative dermatitis, and Stevens-Johnson syndrome. To evaluate the safety and efficacy of oral desensitization by administering incremental dosages of imatinib mesylate to patients with leukemia who have had rashes associated with prior exposure. Ten patients with leukemia and imatinib-associated recurrent rash underwent a 4-hour outpatient oral desensitization procedure. Beginning with 10 ng, we administered oral imatinib elixir in increasing dosages every 15 minutes. Patient outcomes were monitored by a return clinic visit and by telephone follow-up for a median of approximately 3 years. No episodes of anaphylaxis or serious adverse effects occurred during or immediately after desensitization. Four patients (all with urticaria) had no recurrence of rash after desensitization, and 4 had recurrent rash that resolved after temporary glucocorticosteroid and antihistamine administration. Two patients developed a recurrent rash 5 hours and several days after the procedure and were unable to resume therapy. This oral desensitization protocol appears to help some leukemic patients with recurrent rash tolerate imatinib mesylate, thus permitting continuation of this life-prolonging therapy. These findings suggest that some adverse cutaneous reactions to imatinib may be due to a hypersensitivity mechanism rather than a pharmacologic effect.