title: 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.affiliation: Division of Hematology/Oncology, Tufts New England Medical Center, Boston, MA 02111, USA. francine.foss@es.nemc.org
authors.forename: F M
authors.initials: FM
authors.lastname: Foss
authors.forename: P
authors.initials: P
authors.lastname: Bacha
authors.forename: K E
authors.initials: KE
authors.lastname: Osann
authors.forename: M F
authors.initials: MF
authors.lastname: Demierre
authors.forename: T
authors.initials: T
authors.lastname: Bell
authors.forename: T
authors.initials: T
authors.lastname: Kuzel
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D003131:Combined Modality Therapy; D003907:Dexamethasone / Q000627:therapeutic use; D004167:Diphtheria Toxin / Q000009:adverse effects* / Q000627:therapeutic use; D004342:Drug Hypersensitivity / Q000209:etiology / Q000517:prevention & control*; D005260:Female; D005938:Glucocorticoids / Q000627:therapeutic use*; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects* / Q000627:therapeutic use; D000922:Immunotoxins / Q000009:adverse effects* / Q000627:therapeutic use; D007376:Interleukin-2 / Q000009:adverse effects* / Q000627:therapeutic use; D008214:Lymphocytes / Q000276:immunology; D016410:Lymphoma, T-Cell, Cutaneous / Q000188:drug therapy* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011241:Prednisone / Q000627:therapeutic use; D011292:Premedication; D011993:Recombinant Fusion Proteins / Q000009:adverse effects* / Q000627:therapeutic use; D012878:Skin Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D013577:Syndrome; D016896:Treatment Outcome
chemical_list: D004167:Diphtheria Toxin; D005938:Glucocorticoids; D007166:Immunosuppressive Agents; D000922:Immunotoxins; D007376:Interleukin-2; D011993:Recombinant Fusion Proteins; C078456:denileukin diftitox; D003907:Dexamethasone; D011241:Prednisone