title: Phase II trial of denileukin diftitox for relapsed/refractory T-cell non-Hodgkin lymphoma.
abstract: This phase II study evaluated the safety and efficacy of denileukin diftitox, an interleukin-2-diphtheria toxin fusion protein, in relapsed/refractory T-cell non-Hodgkin lymphoma (T-NHL), excluding cutaneous T-cell lymphoma. Eligible patients received denileukin diftitox 18 microg/kg/d x 5 d every 3 weeks for up to eight cycles. Tumour staging was performed every two cycles and the primary endpoint was the objective response rate [complete response (CR) + partial response (PR)]. For 27 patients enrolled, median age: 55 years (range 26-80 years), 70.4% male, and mean prior therapies: 2.5 (range 1-6). Objective responses (six CRs, seven PRs) were achieved in 13 patients (48.1%), stable disease in eight (29.6%) and six (22.2%) had progressive disease. An objective response was achieved in eight of 13 patients (61.5%) with CD25(+) tumours (four CR/four PR) and five of 11 patients (45.5%) with CD25(-) tumours (two CR/three PR). Median progression-free survival was 6 months (range, 1-38+ months). Most adverse reactions were grade 1/2 and transient. No grade 4-5 toxicities were reported. Denileukin diftitox had significant activity and was well tolerated in relapsed/refractory T-NHL, with responses observed in both CD25(+) and CD25(-) tumours. Further studies of denileukin diftitox in combination with other agents are warranted in previously untreated and relapsed/refractory T-NHL.
authors.affiliation: Department of Hematologic Malignancies, Nevada Cancer Institute, Las Vegas, NV 89135, USA. ndang@nvcancer.org
authors.forename: Nam H
authors.initials: NH
authors.lastname: Dang
authors.forename: Barbara
authors.initials: B
authors.lastname: Pro
authors.forename: Fredrick B
authors.initials: FB
authors.lastname: Hagemeister
authors.forename: Felipe
authors.initials: F
authors.lastname: Samaniego
authors.forename: Dan
authors.initials: D
authors.lastname: Jones
authors.forename: Barry I
authors.initials: BI
authors.lastname: Samuels
authors.forename: Maria A
authors.initials: MA
authors.lastname: Rodriguez
authors.forename: Andre
authors.initials: A
authors.lastname: Goy
authors.forename: Jorge E
authors.initials: JE
authors.lastname: Romaguera
authors.forename: Peter
authors.initials: P
authors.lastname: McLaughlin
authors.forename: Ann T
authors.initials: AT
authors.lastname: Tong
authors.forename: Francesco
authors.initials: F
authors.lastname: Turturro
authors.forename: Pamela L
authors.initials: PL
authors.lastname: Walker
authors.forename: Luis
authors.initials: L
authors.lastname: Fayad
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D004167:Diphtheria Toxin / Q000009:adverse effects / Q000627:therapeutic use*; D018572:Disease-Free Survival; D004334:Drug Administration Schedule; D019008:Drug Resistance, Neoplasm; D005221:Fatigue; D005260:Female; D006801:Humans; D007376:Interleukin-2 / Q000009:adverse effects / Q000627:therapeutic use*; D053645:Interleukin-2 Receptor alpha Subunit / Q000032:analysis; D016399:Lymphoma, T-Cell / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy*; D009367:Neoplasm Staging; D011993:Recombinant Fusion Proteins / Q000009:adverse effects / Q000627:therapeutic use; D000637:Transaminases / Q000378:metabolism; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D004167:Diphtheria Toxin; D007376:Interleukin-2; D053645:Interleukin-2 Receptor alpha Subunit; D011993:Recombinant Fusion Proteins; C078456:denileukin diftitox; D000637:Transaminases