Rituximab for steroid-refractory chronic graft-versus-host disease.
B cells may be implicated in the pathophysiology of chronic graft-versus-host disease (GVHD), as evidenced by antibody production against sex-mismatched, Y chromosome-encoded minor HLA antigens in association with chronic GVHD. We therefore designed a phase 1/2 study of anti-B-cell therapy with rituximab in steroid-refractory chronic GVHD. Twenty-one patients were treated with 38 cycles of rituximab. Rituximab was tolerated well, and toxicity was limited to infectious events. The clinical response rate was 70%, including 2 patients with complete responses. Responses were limited to patients with cutaneous and musculoskeletal manifestations of chronic GVHD and were durable through 1 year after therapy. The median dose of prednisone among treated subjects fell from 40 mg/day to 10 mg/day, 1 year after rituximab therapy (P < .001). A chronic GVHD symptom score improved in the majority of treated patients. Antibody titers against Y chromosome-encoded minor HLA antigens fell and remained low, whereas titers against infectious antigens (EBV, tetanus) remained stable or rose during the treatment period. We conclude that specific anti-B-cell therapy with rituximab may be beneficial for patients with steroidrefractory chronic GVHD. This trial was registered at www.clinicaltrials.gov as #NCT00136396.
Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02115, USA. corey_cutler@dfci.harvard.edu
Corey
C
Cutler
David
D
Miklos
Haesook T
HT
Kim
Nathaniel
N
Treister
Sook-Bin
SB
Woo
Don
D
Bienfang
Lloyd B
LB
Klickstein
Jesse
J
Levin
Katherine
K
Miller
Carol
C
Reynolds
Rebecca
R
Macdonell
Mildred
M
Pasek
Stephanie J
SJ
Lee
Vincent
V
Ho
Robert
R
Soiffer
Joseph H
JH
Antin
Jerome
J
Ritz
Edwin
E
Alyea
D000328:Adult; D000911:Antibodies, Monoclonal / Q000008:administration & dosage*; D058846:Antibodies, Monoclonal, Murine-Derived; D001402:B-Lymphocytes / Q000187:drug effects / Q000473:pathology; D002908:Chronic Disease; D004351:Drug Resistance; D005260:Female; D006086:Graft vs Host Disease / Q000188:drug therapy* / Q000473:pathology; D006801:Humans; D008297:Male; D008875:Middle Aged; D009140:Musculoskeletal Diseases / Q000188:drug therapy / Q000209:etiology; D011241:Prednisone / Q000494:pharmacology; D000069283:Rituximab; D016879:Salvage Therapy / Q000379:methods; D012871:Skin Diseases / Q000188:drug therapy / Q000209:etiology; D013256:Steroids / Q000494:pharmacology*
D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D013256:Steroids; D000069283:Rituximab; D011241:Prednisone