Daclizumab, a humanized anti-interleukin-2 receptor alpha chain antibody, for treatment of acute graft-versus-host disease

Blood ◽  
2000 ◽  
Vol 95 (1) ◽  
pp. 83-89 ◽  
Author(s):  
D. Przepiorka ◽  
N. A. Kernan ◽  
C. Ippoliti ◽  
E. B. Papadopoulos ◽  
S. Giralt ◽  
...  
Keyword(s):  
Graft Versus Host Disease ◽  
Interleukin 2 ◽  
Complete Response ◽  
Competitive Inhibitor ◽  
Controlled Study ◽  
Activated Lymphocytes ◽  
Host Disease ◽  
Graft Versus Host ◽  
Interleukin 2 Receptor ◽  
Acute Graft

Abstract Daclizumab, a humanized monoclonal IgG1 directed against the  chain of the interleukin-2 receptor (IL-2R), is a competitive inhibitor of IL-2 on activated lymphocytes. To test the hypothesis that specific inhibition of activated lymphocytes in patients with ongoing acute graft-versus-host disease (GVHD) might ameliorate the process, we treated 43 patients with advanced or steroid-refractory GVHD with daclizumab. The first cohort of 24 patients was treated with daclizumab 1 mg/kg on days 1, 8, 15, 22, and 29. On day 43, the complete response (CR) rate was 29% (95% confidence interval [CI], 13%-51%). Survival on day 120 was 29% (95% CI, 13%-51%). A second cohort of 19 patients was treated with daclizumab 1 mg/kg on days 1, 4, 8, 15, and 22. For these patients, the CR rate on day 43 was 47% (95% CI, 24%-71%), and survival on day 120 was 53% (95% CI, 29%-76%). There were no infusion-related reactions and no serious side effects related to daclizumab. Following treatment, there was a reduction in serum concentrations of soluble IL-2R and peripheral blood CD3 + 25+ lymphocytes, but these changes were not predictive of response. Daclizumab has substantial activity for the treatment of acute GVHD, and the second regimen evaluated is recommended for a controlled study. (Blood, 2000; 95:83-89)

Daclizumab, a humanized anti-interleukin-2 receptor alpha chain antibody, for treatment of acute graft-versus-host disease

Blood ◽  
2000 ◽  
Vol 95 (1) ◽  
pp. 83-89 ◽  
Author(s):  
D. Przepiorka ◽  
N. A. Kernan ◽  
C. Ippoliti ◽  
E. B. Papadopoulos ◽  
S. Giralt ◽  
...  
Keyword(s):  
Graft Versus Host Disease ◽  
Interleukin 2 ◽  
Complete Response ◽  
Competitive Inhibitor ◽  
Controlled Study ◽  
Activated Lymphocytes ◽  
Host Disease ◽  
Graft Versus Host ◽  
Interleukin 2 Receptor ◽  
Acute Graft

Daclizumab, a humanized monoclonal IgG1 directed against the  chain of the interleukin-2 receptor (IL-2R), is a competitive inhibitor of IL-2 on activated lymphocytes. To test the hypothesis that specific inhibition of activated lymphocytes in patients with ongoing acute graft-versus-host disease (GVHD) might ameliorate the process, we treated 43 patients with advanced or steroid-refractory GVHD with daclizumab. The first cohort of 24 patients was treated with daclizumab 1 mg/kg on days 1, 8, 15, 22, and 29. On day 43, the complete response (CR) rate was 29% (95% confidence interval [CI], 13%-51%). Survival on day 120 was 29% (95% CI, 13%-51%). A second cohort of 19 patients was treated with daclizumab 1 mg/kg on days 1, 4, 8, 15, and 22. For these patients, the CR rate on day 43 was 47% (95% CI, 24%-71%), and survival on day 120 was 53% (95% CI, 29%-76%). There were no infusion-related reactions and no serious side effects related to daclizumab. Following treatment, there was a reduction in serum concentrations of soluble IL-2R and peripheral blood CD3 + 25+ lymphocytes, but these changes were not predictive of response. Daclizumab has substantial activity for the treatment of acute GVHD, and the second regimen evaluated is recommended for a controlled study. (Blood, 2000; 95:83-89)

PREVENTION OF ACUTE GRAFT-VERSUS-HOST DISEASE BY MONOCLONAL ANTIBODY TO INTERLEUKIN-2 RECEPTOR

The Lancet ◽  
1989 ◽  
Vol 333 (8650) ◽  
pp. 1333-1334 ◽  
Author(s):  
Didier Blaise ◽  
Dominique Maraninchi ◽  
Claude Mawas ◽  
AnneMarie Stoppa ◽  
Michel Hirn ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
Graft Versus Host Disease ◽  
Interleukin 2 ◽  
Host Disease ◽  
Graft Versus Host ◽  
Interleukin 2 Receptor ◽  
Acute Graft

Efficacy of the interleukin-2 receptor antagonist basiliximab in steroid-refractory acute graft-versus-host disease

2005 ◽  
Vol 130 (4) ◽  
pp. 568-574 ◽  
Author(s):  
Martin Schmidt-Hieber ◽  
Thomas Fietz ◽  
Wolfgang Knauf ◽  
Lutz Uharek ◽  
Werner Hopfenmuller ◽  
...  
Keyword(s):  
Receptor Antagonist ◽  
Graft Versus Host Disease ◽  
Interleukin 2 ◽  
Host Disease ◽  
Graft Versus Host ◽  
Interleukin 2 Receptor ◽  
Steroid Refractory ◽  
Acute Graft

scholarly journals Treatment of corticosteroid resistant acute graft-versus-host disease by in vivo administration of anti-interleukin-2 receptor monoclonal antibody (B-B10) [see comments]

Blood ◽  
1990 ◽  
Vol 75 (4) ◽  
pp. 1017-1023 ◽  
Author(s):  
P Herve ◽  
J Wijdenes ◽  
JP Bergerat ◽  
P Bordigoni ◽  
N Milpied ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
Graft Versus Host Disease ◽  
Interleukin 2 ◽  
Complete Response ◽  
Host Disease ◽  
Graft Versus Host ◽  
In Vivo Administration ◽  
Acute Graft ◽  
Receptor Monoclonal Antibody

Abstract In a multicenter pilot study, 32 patients showing steroid-resistant acute graft-versus-host disease (GVHD) were treated by in vivo administration of anti-interleukin-2 (IL-2) receptor monoclonal antibody (MoAb B-B10). Twenty-three patients received marrow from HLA- matched related donors, four from matched unrelated donors and five from partially matched related donors. The overall grade of GVHD was II in 16 patients, III in two, and IV in five. Five milligrams of B-B10 MoAb was infused in bolus daily for 10 days and then every second day for a further 10 days in an attempt to reduce GVHD recurrence. No clinical side effects were noted during the B-B10 treatment period. A complete response (CR) acute GVHD was achieved in 21 patients (65.6%). Six patients (18.7%) showed partial improvement (PR) and 5 patients (15.6%) no response (NR). A significant factor associated with GVHD response was the delay between the onset of the GVHD and the first day of B-B10 infusion. The earlier B-B10 was introduced, the greater the probability of CR (P = .03). There was no correlation between the serum B-B10 level and GVHD response (P = .69). There was, however, a significant correlation between the clinical response and the B-B10 kinetics as a function of time: serum B-B10 levels attained a plateau level more rapidly in the CR group than in the PR/NR group. Among the 26 complete and partial evaluable responders, GVHD recurred in 10 cases (38.4%). Host anti-B-B10 MoAb immune response occurred in only one (7.1%) of the 14 patients analyzed. Fourteen of the 32 patients (43.7%) are currently alive between 2 and 14 months after GVHD treatment with B- B10 was completed.

scholarly journals Therapy for severe refractory acute graft-versus-host disease with basiliximab, a selective interleukin-2 receptor antagonist

2006 ◽  
Vol 37 (10) ◽  
pp. 961-965 ◽  
Author(s):  
V A M Funke ◽  
C R de Medeiros ◽  
D C Setúbal ◽  
J Ruiz ◽  
M A Bitencourt ◽  
...  
Keyword(s):  
Receptor Antagonist ◽  
Graft Versus Host Disease ◽  
Interleukin 2 ◽  
Host Disease ◽  
Graft Versus Host ◽  
Interleukin 2 Receptor ◽  
Acute Graft

scholarly journals Treatment of corticosteroid resistant acute graft-versus-host disease by in vivo administration of anti-interleukin-2 receptor monoclonal antibody (B-B10) [see comments]

Blood ◽  
1990 ◽  
Vol 75 (4) ◽  
pp. 1017-1023 ◽  
Author(s):  
P Herve ◽  
J Wijdenes ◽  
JP Bergerat ◽  
P Bordigoni ◽  
N Milpied ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
Graft Versus Host Disease ◽  
Interleukin 2 ◽  
Complete Response ◽  
Host Disease ◽  
Graft Versus Host ◽  
In Vivo Administration ◽  
Acute Graft ◽  
Receptor Monoclonal Antibody

In a multicenter pilot study, 32 patients showing steroid-resistant acute graft-versus-host disease (GVHD) were treated by in vivo administration of anti-interleukin-2 (IL-2) receptor monoclonal antibody (MoAb B-B10). Twenty-three patients received marrow from HLA- matched related donors, four from matched unrelated donors and five from partially matched related donors. The overall grade of GVHD was II in 16 patients, III in two, and IV in five. Five milligrams of B-B10 MoAb was infused in bolus daily for 10 days and then every second day for a further 10 days in an attempt to reduce GVHD recurrence. No clinical side effects were noted during the B-B10 treatment period. A complete response (CR) acute GVHD was achieved in 21 patients (65.6%). Six patients (18.7%) showed partial improvement (PR) and 5 patients (15.6%) no response (NR). A significant factor associated with GVHD response was the delay between the onset of the GVHD and the first day of B-B10 infusion. The earlier B-B10 was introduced, the greater the probability of CR (P = .03). There was no correlation between the serum B-B10 level and GVHD response (P = .69). There was, however, a significant correlation between the clinical response and the B-B10 kinetics as a function of time: serum B-B10 levels attained a plateau level more rapidly in the CR group than in the PR/NR group. Among the 26 complete and partial evaluable responders, GVHD recurred in 10 cases (38.4%). Host anti-B-B10 MoAb immune response occurred in only one (7.1%) of the 14 patients analyzed. Fourteen of the 32 patients (43.7%) are currently alive between 2 and 14 months after GVHD treatment with B- B10 was completed.

Safety and efficacy of denileukin diftitox in patients with steroid-refractory acute graft-versus-host disease after allogeneic hematopoietic stem cell transplantation

Blood ◽  
2004 ◽  
Vol 104 (4) ◽  
pp. 1224-1226 ◽  
Author(s):  
Vincent T. Ho ◽  
David Zahrieh ◽  
Ephraim Hochberg ◽  
Eileen Micale ◽  
Jesse Levin ◽  
...  
Keyword(s):  
Graft Versus Host Disease ◽  
Phase 1 ◽  
Interleukin 2 ◽  
Maximum Tolerated Dose ◽  
Hematopoietic Stem ◽  
Host Disease ◽  
Graft Versus Host ◽  
Denileukin Diftitox ◽  
Steroid Refractory ◽  
Acute Graft

Abstract 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 μg/kg intravenously on days 1 and 15; 18 received 9 μg/kg intravenously on days 1, 3, 5, 15, 17, and 19; and 5 received 9 μg/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. (Blood. 2004;104:1224-1226)

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