Phase II trial of denileukin diftitox for relapsed/refractory T-cell non-Hodgkin lymphoma.
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.
Dang
Nam H
NH
Department of Hematologic Malignancies, Nevada Cancer Institute, Las Vegas, NV 89135, USA. ndang@nvcancer.org
Pro
Barbara
B
Hagemeister
Fredrick B
FB
Samaniego
Felipe
F
Jones
Dan
D
Samuels
Barry I
BI
Rodriguez
Maria A
MA
Goy
Andre
A
Romaguera
Jorge E
JE
McLaughlin
Peter
P
Tong
Ann T
AT
Turturro
Francesco
F
Walker
Pamela L
PL
Fayad
Luis
L
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
D000970:Antineoplastic Agents; D004167:Diphtheria Toxin; D007376:Interleukin-2; D053645:Interleukin-2 Receptor alpha Subunit; D011993:Recombinant Fusion Proteins; C078456:denileukin diftitox; D000637:Transaminases