Denileukin diftitox for the treatment of steroid-resistant acute graft-versus-host disease.
Acute graft-versus-host disease (aGVHD) is partly mediated through activated T cells, and these cells are known to express the high-affinity receptor for interleukin 2 (IL-2R). Denileukin diftitox is composed of human IL-2 and diphtheria toxin that is cytotoxic to activated lymphocytes expressing the high-affinity IL-2R. We describe the results of a phase II study of denileukin diftitox in 22 patients with steroid-resistant aGVHD. Twenty patients were treated at dose level 1 (4.5 microg/kg daily on days 1-5 and then weekly on study days 8, 15, 22, and 29), and 2 patients were treated at dose level 2 (9.0 microg/kg delivered on the same schedule). Dose level 2 was associated with grade 3/4 renal and hepatic toxicity and vascular leak syndrome, and no further patients were treated at this level. Dose level 1 was generally well tolerated. The response of aGVHD was assessed at study days 36 and 100. Nine patients (41%) responded, all with a complete response at study day 36, and 6 patients (27%) responded at study day 100 (4 complete responses and 2 partial responses). Denileukin diftitox has promising activity in steroid-resistant aGVHD, and further study is warranted.
Shaughnessy
Paul J
PJ
Texas Transplant Institute, San Antonio 78229, USA. Paul.Shaughnessy@MHShealth.com
Bachier
Carlos
C
Grimley
Michael
M
Freytes
Cesar O
CO
Callander
Natalie S
NS
Essell
James H
JH
Flomenberg
Neal
N
Selby
George
G
Lemaistre
C F
CF
D000208:Acute Disease; D019559:Capillary Leak Syndrome / Q000139:chemically induced; D056486:Chemical and Drug Induced Liver Injury; D004167:Diphtheria Toxin / Q000008:administration & dosage* / Q000633:toxicity; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004351:Drug Resistance; D006086:Graft vs Host Disease / Q000188:drug therapy*; D019337:Hematologic Neoplasms / Q000188:drug therapy / Q000628:therapy; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects; D006801:Humans; D007376:Interleukin-2 / Q000008:administration & dosage* / Q000633:toxicity; D011993:Recombinant Fusion Proteins / Q000008:administration & dosage / Q000633:toxicity; D012074:Remission Induction; D013256:Steroids
D004167:Diphtheria Toxin; D007376:Interleukin-2; D011993:Recombinant Fusion Proteins; D013256:Steroids; C078456:denileukin diftitox