Weekly rituximab followed by monthly rituximab treatment for steroid-refractory chronic graft-versus-host disease: results from a prospective, multicenter, phase II study.
BACKGROUND
Since it was suggested that B cells play a role in the pathogenesis of chronic graft-versus-host disease, rituximab, an anti-CD20 monoclonal antibody targeting B cells, has been shown to be effective in steroid-refractory, chronic graft-versus-host disease. However, most of the data were from small numbers of patients or retrospective analyses. We, therefore, conducted a multicenter phase II study to confirm the efficacy of this treatment strategy that targets B cells.


METHODS
We diagnosed and evaluated chronic graft-versus-host disease according to the National Institute of Health criteria for clinical trials on this condition. The treatment consisted of weekly intravenous infusions of rituximab for 4 weeks followed by monthly rituximab for 4 months. We evaluated the patients' responses and monitored their disease activity until their final visit, which was on day 365. We also assessed the patients' subsequent quality of life and serum levels of B-cell-activating factor of the tumor necrosis factor family.


RESULTS
Among 37 patients enrolled (median age, 29 years; range 8-57 years), 32 patients responded to rituximab with 8 complete and 24 partial responses. Twenty-one patients maintained their response for 1 year, so their steroid treatment was discontinued or its dose reduced (21/37, or 56.8%), and their scores representing quality of life were improved although these changes were not statistically significant. The responses were better for clinical manifestations of the skin, oral cavity and musculoskeletal system (response rate, 71.4-100%) than for other organs. However, infectious complications and primary disease relapse accounted for the majority of treatment failure. The pre-treatment serum level of B cell-activating factor of the tumor necrosis factor family was not associated with better treatment outcome (P=0.147).


CONCLUSIONS
Rituximab could improve clinical responses and quality of life of patients with steroid-refractory chronic graft-versus-host disease, although such patients may need active prophylaxis against infection.
Kim
Seok Jin
SJ
Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
Lee
Jong Wook
JW
Jung
Chul Won
CW
Min
Chang Ki
CK
Cho
Bin
B
Shin
Ho Jin
HJ
Chung
Joo Seop
JS
Kim
Hawk
H
Lee
Won Sik
WS
Joo
Young Don
YD
Yang
Deok-Hwan
DH
Kook
Hoon
H
Kang
Hyoung Jin
HJ
Ahn
Hyo Seop
HS
Yoon
Sung-Soo
SS
Sohn
Sang Kyun
SK
Min
Yoo Hong
YH
Min
Woo-Sung
WS
Park
Hee-Sook
HS
Won
Jong Ho
JH
D000293:Adolescent; D000328:Adult; D058846:Antibodies, Monoclonal, Murine-Derived / Q000008:administration & dosage*; D053264:B-Cell Activating Factor / Q000097:blood; D001402:B-Lymphocytes / Q000378:metabolism; D056486:Chemical and Drug Induced Liver Injury / Q000097:blood / Q000628:therapy; D002648:Child; D002908:Chronic Disease; D003920:Diabetes Mellitus / Q000097:blood / Q000628:therapy; D005260:Female; D006086:Graft vs Host Disease / Q000097:blood / Q000188:drug therapy* / Q000378:metabolism; D019337:Hematologic Neoplasms / Q000097:blood / Q000628:therapy; D006801:Humans; D007155:Immunologic Factors / Q000008:administration & dosage*; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D000069283:Rituximab; D033581:Stem Cell Transplantation; D013256:Steroids / Q000627:therapeutic use; D014184:Transplantation, Homologous; D014376:Tuberculosis / Q000097:blood / Q000628:therapy
D058846:Antibodies, Monoclonal, Murine-Derived; D053264:B-Cell Activating Factor; D007155:Immunologic Factors; D013256:Steroids; D000069283:Rituximab