Weekly rituximab followed by monthly rituximab treatment for steroid-refractory chronic graft-versus-host disease: results from a prospective, multicenter, phase II study - PubMed (original) (raw)

Clinical Trial

. 2010 Nov;95(11):1935-42.

doi: 10.3324/haematol.2010.026104. Epub 2010 Jul 27.

Jong Wook Lee, Chul Won Jung, Chang Ki Min, Bin Cho, Ho Jin Shin, Joo Seop Chung, Hawk Kim, Won Sik Lee, Young Don Joo, Deok-Hwan Yang, Hoon Kook, Hyoung Jin Kang, Hyo Seop Ahn, Sung-Soo Yoon, Sang Kyun Sohn, Yoo Hong Min, Woo-Sung Min, Hee-Sook Park, Jong Ho Won

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Clinical Trial

Weekly rituximab followed by monthly rituximab treatment for steroid-refractory chronic graft-versus-host disease: results from a prospective, multicenter, phase II study

Seok Jin Kim et al. Haematologica. 2010 Nov.

Abstract

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.

Design and 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.

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Figures

Figure 1.

Figure 1.

(A) Treatment schedule and response evaluation. (B) The time to maximal response in 37 patients. The median time to maximal response was day 29, and the range was from day 0 (for non-responders) to day 252.

Figure 2.

Figure 2.

(A) In the ITT analysis of quality of life, patients reported increased scores in six domains (RP, BP, GH, SF, RE and MH) although only the effects on RP and BP were statistically significant (P<0.05). (B) PP analysis, including only patients with complete follow-up through day 365 showed a tendency toward improvement in all domains of the SF36 quality of life questionnaire although not statistically significant. GH, general health perceptions; PF, physical function; MH, general mental health; RP, role function limitation due to physical problems; RE, role function limitation due to emotional problems; BP, bodily pain; VT, vitality; SF, social function; PCS, physical component summary; MCS, mental component summary

Figure 3.

Figure 3.

Serial changes in serum BAFF and immunoglobulins. Serum BAFF increased continuously, but was inversely correlated with the sustained decrease in immune globulins.

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