Biological correlates of acute hypersensitivity events with DAB(389)IL-2 (denileukin diftitox, ONTAK) in cutaneous T-cell lymphoma: decreased frequency and severity with steroid premedication.

Abstract

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.

• Authors: F M Foss, P Bacha, K E Osann, M F Demierre, T Bell, T Kuzel
• Journal: Clinical lymphoma (Clin Lymphoma) Vol. 1 Issue 4 Pg. 298-302 (Mar 2001) ISSN: 1526-9655 [Print] United States
• PMID: 11707845 (Publication Type: Clinical Trial, Clinical Trial, Phase III, Journal Article, Multicenter Study)

Chemical References

• Diphtheria Toxin
• Glucocorticoids
• Immunosuppressive Agents
• Immunotoxins
• Interleukin-2
• Recombinant Fusion Proteins
• denileukin diftitox
• Dexamethasone
• Prednisone

Topics

• Adult
• Aged
• Aged, 80 and over
• Combined Modality Therapy
• Dexamethasone (therapeutic use)
• Diphtheria Toxin (adverse effects, therapeutic use)
• Drug Hypersensitivity (etiology, prevention & control)
• Female
• Glucocorticoids (therapeutic use)
• Humans
• Immunosuppressive Agents (adverse effects, therapeutic use)
• Immunotoxins (adverse effects, therapeutic use)
• Interleukin-2 (adverse effects, therapeutic use)
• Lymphocytes (immunology)
• Lymphoma, T-Cell, Cutaneous (drug therapy, metabolism)
• Male
• Middle Aged
• Neoplasm Staging
• Prednisone (therapeutic use)
• Premedication
• Recombinant Fusion Proteins (adverse effects, therapeutic use)
• Skin Neoplasms (drug therapy, metabolism)
• Syndrome
• Treatment Outcome