Mycophenylate Mofetil for Treatment of Chronic GVHD

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DESCRIPTION (provided by applicant): Chronic graft-versus-host disease (GVHD) occurs in approximately 60% of patients who survive for more than 3 months after hematopoietic stem cell transplantation from an allogeneic donor for treatment of hematological malignancy. Apart from recurrent malignancy, chronic GVHD is the leading cause of death and morbidity in this patient population. High-dose glucocorticoids have long served as the mainstay of treatment for chronic GVHD, at the cost of considerable morbidity. The four specific aims of this project seek to develop new approaches for treatment of chronic GVHD. Specific Aim 1 proposes to complete a multicenter, phase III double-blind clinical trial to evaluate the efficacy of mycophenolate mofetil (MMF) for treatment of newly diagnosed chronic GVHD. In Specific Aim 2, data from the current study will be combined with data from a similar study sponsored by a European consortium for a joint analysis results. In addition to testing the efficacy and safety of MMF for initial systemic treatment of chronic GVHD, the analysis will seek to validate recommendations of the NIH Consensus Development project with respect to criteria for staging the severity the chronic GVHD, and to validate specific manifestations of acute GVHD that occur in the "overlap" variant of chronic GVHD as prognostic indicators of survival after the diagnosis of chronic GVHD. In Specific Aim 3, data from the current study will be used to validate prognostic factors identified in previous retrospective studies, to test other prognostic characteristics present at the diagnosis of chronic GVHD, and to develop response criteria that could be used in future clinical trials. In Specific Aim 4, data from the current study will be used to test the hypothesis that major improvement in manifestations of chronic GVHD combined with a major reduction of glucocorticoid dose at 6 months after starting systemic immunosuppressive treatment is associated with subsequent early resolution of chronic GVHD and withdrawal of all immunosuppressive treatment. PUBLIC HEALTH RELEVANCE: Results of the proposed studies will 1) define the efficacy and safety of adding mycophenolate mofetil to standard initial systemic immunosuppressive regimens for treatment of chronic graft-versus-host disease (GVHD), and 2) provide a rich source of information that will be highly useful for the design of future clinical trials. An important question to be addressed is whether the outcomes for patients with chronic GVHD can be improved by more intensive immunosuppressive treatment at the onset of the disease.