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

Abstract

BackgroundSince 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 MethodsWe 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. ResultsAmong 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). ConclusionsRituximab 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. (ClinicalTrials.

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“…Patients who switched treatment regimens from monthly rituximab maintenance to tocilizumab owing to a lack of clinical improvement were included in the tocilizumab group. In the additional rituximab group, rituximab was administrated in 1-month intervals, beginning at 1 month after the last infusion of weekly rituximab, with the same dosage (375 mg/m 2 ) [10].…”

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