Safety and efficacy of denileukin diftitox in patients with steroid-refractory acute graft-versus-host disease after allogeneic hematopoietic stem cell transplantation.
Denileukin diftitox (Ontak), a recombinant protein composed of human interleukin 2 (IL-2) fused to diphtheria toxin, has selective cytotoxicity against activated lymphocytes expressing the high-affinity IL-2 receptor. We conducted a phase 1 study of denileukin diftitox in 30 patients with steroid refractory acute graft-versus-host disease (GVHD). Seven patients received 9 microg/kg intravenously on days 1 and 15; 18 received 9 microg/kg intravenously on days 1, 3, 5, 15, 17, and 19; and 5 received 9 microg/kg intravenously on days 1 to 5 and 15 to 19. Hepatic transaminase elevation was the dose-limiting toxicity (DLT), and dose level 2 was the maximum tolerated dose (MTD). Overall, 71% of patients responded with complete resolution (12 of 24; 50%) or partial resolution (5 of 24; 21%) of GVHD. Eight of 24 patients (33%) are alive at 6.3 to 24.6 months (median, 7.2 months). Denileukin diftitox is tolerable and has promising activity in steroid-refractory acute GVHD.
Ho
Vincent T
VT
Dana-Farber Cancer Institute, 44 Binney St, D1B21, Boston, MA 02115, USA. vtho@partners.org
Zahrieh
David
D
Hochberg
Ephraim
E
Micale
Eileen
E
Levin
Jesse
J
Reynolds
Carol
C
Steckel
Steve
S
Cutler
Corey
C
Fisher
David C
DC
Lee
Stephanie J
SJ
Alyea
Edwin P
EP
Ritz
Jerome
J
Soiffer
Robert J
RJ
Antin
Joseph H
JH
D000208:Acute Disease; D000328:Adult; D000368:Aged; D004167:Diphtheria Toxin / Q000008:administration & dosage* / Q000633:toxicity; D004305:Dose-Response Relationship, Drug; D004351:Drug Resistance; D005260:Female; D006086:Graft vs Host Disease / Q000188:drug therapy*; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects*; D006801:Humans; D007376:Interleukin-2 / Q000008:administration & dosage* / Q000633:toxicity; D008213:Lymphocyte Activation; D008212:Lymphocyte Depletion; D008297:Male; D008875:Middle Aged; D011993:Recombinant Fusion Proteins / Q000008:administration & dosage* / Q000633:toxicity; D016879:Salvage Therapy; D013256:Steroids; D013601:T-Lymphocytes / Q000276:immunology; D014184:Transplantation, Homologous; D016896:Treatment Outcome
D004167:Diphtheria Toxin; D007376:Interleukin-2; D011993:Recombinant Fusion Proteins; D013256:Steroids; C078456:denileukin diftitox