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Blood, 1 October 2001, Vol. 98, No. 7, pp. 2052-2058
CLINICAL OBSERVATIONS, INTERVENTIONS, AND THERAPEUTIC TRIALS
Treatment of steroid-refractory acute graft-versus-host disease
with anti-CD147 monoclonal antibody ABX-CBL
H. Joachim Deeg,
Bruce
R. Blazar,
Brian J. Bolwell,
Gwynn D. Long,
Friedrich Schuening,
John Cunningham,
Robert M. Rifkin,
Sunil Abhyankar,
Adrienne D. Briggs,
Richard Burt,
John Lipani,
Lorin K. Roskos,
J.
Michael White,
Nancy Havrilla,
Gisela Schwab, and
Helen E. Heslop
From the Fred Hutchinson Cancer Research Center,
Seattle, WA; Fairview University Medical Center, Minneapolis, MN;
Cleveland Clinic Foundation, OH; Duke University Medical Center,
Durham, NC; University of Wisconsin Hospital and Clinic, Madison; St
Jude Children's Research Hospital, Memphis, TN; Rocky Mountain Cancer
Center, Denver, CO; Center of Cancer Treatment and Research, Palmetto
Richland Memorial Hospital, Columbia, SC; Arizona Cancer Center,
Tucson; Northwestern University, Chicago, IL; Abgenix, Inc, Fremont,
CA; J. M. White Associates, Mt Vernon, WA; Baylor College
of Medicine, Houston, TX.
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. Among 51 patients evaluable for efficacy, 26 (51%) responded,
including 13 with complete responses (CR) and 13 with partial responses
(PR). CR lasting 14 days or longer or PR lasting 7 days or longer
occurred in 21 (41%; 8 CR, 13 PR) patients, including 19 of 43 (44%)
patients who received 0.1 to 0.3 mg/kg ABX-CBL and 2 of 8 (25%)
patients given 0.01 mg/kg per day. Myalgias at doses 0.2 mg/kg or
greater were dose limiting and resolved without sequelae. Causes of
death included organ failure, progressive GVHD, and infection. No death
was attributed to ABX-CBL. At 6 months after the initiation of ABX-CBL
therapy, 26 (44%) patients were surviving. These results are
encouraging. Further studies on the use of ABX-CBL in the management of
GVHD are warranted.
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