Anti-interleukin-2 receptor monoclonal antibody (BT 563) in the treatment of severe acute GVHD refractory to systemic corticosteroid therapy.
Fourteen patients with corticosteroid-resistant acute GVHD were treated with a murine monoclonal antibody to the pp55 interleukin-2 (IL-2) receptor (MoAb BT 563). Nine of the 14 patients had also failed Xoma-Zyme-H65 as GVHD prophylaxis and/or treatment. Seven patients had received HLA-matched sibling donor bone marrow transplants, five had received HLA-matched transplants from unrelated volunteer donors, and two had received one-antigen mismatched transplants from unrelated volunteer donors. At the time of MoAb BT 563 therapy, the overall clinical grading of acute GVHD (Seattle grading system) was as follows: grade II--one patient, grade III--four patients, and grade IV--nine patients. MoAb BT 563 was administered as a short iv infusion of 5 mg daily for 10 doses, followed by 5 mg on alternate days for a further five doses. A complete response (CR) was observed in four patients (28%), and a partial response (PR) in four patients (28%). All four complete responders were treated within 28 days of first onset of grade > or = II acute GVHD. Four patients (three CR, one PR) remain alive. One complete responder subsequently died from chronic GVHD. MoAb BT 563 administration was well tolerated in all 14 patients; no significant toxicity was observed. We conclude that MoAb BT 563 directed against the IL-2 receptor on activated T lymphocytes may be useful in treating corticosteroid-resistant acute GVHD if given early, but that it is of limited value in attempting to rescue patients with far-advanced refractory acute GVHD.(ABSTRACT TRUNCATED AT 250 WORDS)
Cuthbert
R J
RJ
Leukemia/Bone Marrow Transplantation Program of British Columbia, Division of Hematology, Vancouver General Hospital, Canada.
Phillips
G L
GL
Barnett
M J
MJ
Nantel
S H
SH
Reece
D E
DE
Shepherd
J D
JD
Klingemann
H G
HG
D000305:Adrenal Cortex Hormones / Q000627:therapeutic use*; D000328:Adult; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D016026:Bone Marrow Transplantation; D004305:Dose-Response Relationship, Drug; D004351:Drug Resistance; D005260:Female; D006086:Graft vs Host Disease / Q000209:etiology / Q000401:mortality / Q000517:prevention & control*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D015375:Receptors, Interleukin-2 / Q000276:immunology*; D015996:Survival Rate
D000305:Adrenal Cortex Hormones; D000911:Antibodies, Monoclonal; D015375:Receptors, Interleukin-2