Biological Correlates of Acute Hypersensitivity Events with DAB389IL-2 (Denileukin Diftitox, ONTAK®) in Cutaneous T-Cell Lymphoma: Decreased Frequency and Severity with Steroid Premedication

Autor: Francine M. Foss, Patricia Bacha, Kathryn E. Osann, Marie France Demierre, Tracy Bell, Timothy Kuzel
Rok vydání: 2001
Předmět:
Zdroj: Clinical Lymphoma. 1:298-302
ISSN: 1526-9655
DOI: 10.3816/clm.2001.n.005
Popis: DAB(389)IL-2 (denileukin diftitox, ONTAK) is a cytokine-targeted fusion protein that delivers the catalytic domain of diphtheria toxin to lymphoma cells expressing the interleukin-2 receptor (IL-2R). In phase I and phase III studies of DAB(389)IL-2 in patients with cutaneous T-cell lymphoma (CTCL), non-Hodgkin's lymphoma, and Hodgkin's disease in which premedications were limited to diphenhydramine and acetaminophen, acute infusion-related hypersensitivity reactions occurred in 70% of patients and vascular leak syndrome (VLS) in 27%, resulting in discontinuation of therapy in 29% of patients. There was no correlation between the dose or half-life of DAB(389)IL-2 and the occurrence of hypersensitivity events or VLS. To explore whether steroid premedication would improve the tolerability of DAB(389)IL-2, we treated 15 patients with CTCL with either dexamethasone or prednisone prior to each dose of DAB(389)IL-2. The incidence of acute infusion events was significantly decreased, with only three patients experiencing acute infusion events (one grade 4) and only two patients developing clinically apparent VLS. Grade 3 skin rash occurred in two patients and moderately severe asthenia in nine patients. A significantly improved response rate of 60% was noted with the use of steroid premedication compared to prior studies in which steroids were prohibited. We conclude that steroid premedication significantly improves the tolerability of DAB(389)IL-2 without compromising the clinical response.
Databáze: OpenAIRE
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