Treatment of steroid-refractory acute graft-versus-host disease with anti-CD147 monoclonal antibody ABX-CBL

Abstract

ABX-CBL, an immunoglobulin M murine monoclonal antibody, recognizes CD147 and initiates cell killing through complement-mediated lysis. In a dose-finding trial, 27 patients with steroid-refractory acute graft-versus-host disease (GVHD) received ABX-CBL at 0.01 (presumed no effect dose), 0.1, 0.2, or 0.3 mg/kg per day, and an additional 32 patients were given ABX-CBL at 0.2 or 0.15 mg/kg per day. All patients had undergone allogeneic transplantation for malignant or nonmalignant disorders and received GVHD prophylaxis, generally with methotrexate-and cyclosporine-containing regimens. None responded to methylprednisolone, given for a minimum of 3 days. ABX-CBL was started 20 to 236 (median, 47) days after transplantation; it was given for 7 consecutive days and was followed by 2 infusions per week for 2 more weeks.

Mycophenolate mofetil for the management of steroid-refractory acute graft vs host disease

“…5,[8][9][10][11] A number of therapeutic agents directed at the immune cascade underlying aGVHD have shown modest activity in steroid-refractory aGVHD. [12][13][14][15][16][17][18][19][20][21][22][23][24][25][26][27][28][29][30] Mycophenolate mofetil (MMF), whose metabolite mycophenolic acid inhibits the de novo synthesis of purines in lymphocytes, has probable efficacy in the treatment of aGVHD, based on three small case series that cumulatively reported 17 cases in which MMF was used for initial therapy for aGVHD, and 16 cases with glucocorticoidrefractory aGVHD. [31][32][33] Here, we report outcomes in a series of 27 recipients of allogeneic hematopoietic cell transplantation treated with MMF as salvage therapy for steroid-refractory aGVHD.…”

A phase 2/3 multicenter randomized clinical trial of ABX-CBL versus ATG as secondary therapy for steroid-resistant acute graft-versus-host disease

“…Although the response rate for ABX-CBL was similar to that observed in previous studies, 18,19 there was no clinically or statistically significant advantage in regard to treatment response using ABX-CBL compared with ATG, and survival was sufficiently unfavorable on ABX-CBL that one can rule out even moderate improvement relative to ATG in this randomized risk-stratified trial. The duration of response was also similar between the treatment groups despite the shorter half-life of ABX-CBL (15-19 hours) versus ATG (5.7 Ϯ 3 days).…”

“…18 In a subsequent phase 1-2 trial of 59 patients with steroid-resistant acute GVHD, patients received ABX-CBL at 0.01, 0.1, 0.2, or 0.3 mg/kg per day, and an additional 32 patients received ABX-CBL at 0.2 or 0.15 mg/kg per day. 19 Among 51 evaluable patients, overall response was observed in 26 (51%), including CRs in 13 patients and PR in 13 patients. Mylagias at doses of 0.2 mg/kg or higher were dose limiting but resolved without sequelae.…”

“…Mylagias at doses of 0.2 mg/kg or higher were dose limiting but resolved without sequelae. 19 This current report describes the results of a multicenter, open-label, randomized clinical trial comparing ABX-CBL to equine ATG (Atgam) in 95 HCT recipients with steroid-resistant acute GVHD.…”

Pre-emptive treatment of acute GVHD: a randomized multicenter trial of rabbit anti-thymocyte globulin, given on day+7 after alternative donor transplants

“…2,3 This being the case, it comes as no surprise that treatment of acute GVHD is rather unsuccessful and has made little or no progress in the past 30 years. 4 This is true for conventional immunosuppression with steroids and anti-thymocyte globulin (ATG), 5 as well as for MoABs directed against IL2 receptors, TNF or ABX, [6][7][8][9][10] with one recent exception: 11 it should be noted that in a recent CIBMTR (Center for International Blood and Marrow Transplant Research) trial, etanercept has not proven to be superior to mycophenolate, in combination with steroids (unpublished).…”