Mycophenolate Mofetil in the treatment of acute and chronic GVHD in hematopoietic stem cell transplant patients: four years of experience

Evaluation of mycophenolate mofetil for initial treatment of chronic graft-versus-host disease

“…First, clinical trials should use randomized designs whenever possible. Case-series reports and uncontrolled phase 2 studies suggested encouraging results with the use of MMF for treatment of steroid-refractory chronic GVHD, [6][7][8][9][10][11][12][13][14][15] but our results with the use of MMF for initial treatment of chronic GVHD offer no support for the use of MMF in the management of steroid-refractory chronic GVHD. Second, the field would benefit from a higher level of enthusiasm and support for enrolling patients in clinical trials.…”

“…[6][7][8][9][10][11][12][13][14][15] Moreover, the tolerability of MMF and ease of oral administration for prolonged periods of time made MMF an attractive alternative among other agents that could have been tested for efficacy in the initial treatment of chronic GVHD. Several hypothetical a priori explanations could be considered as possibly accounting for an (14) .07…”

“…Instead, the study was based on results of previous reports suggesting the efficacy of MMF for treatment of steroid-refractory chronic GVHD, [6][7][8][9][10][11][12][13][14][15] and the proposed effect size was based on the number of patients who could be enrolled in a multicenter study within a reasonable period of time. Even so, the negative results of this study did not simply reflect an overstringent primary endpoint or an unrealistic effect size because the much less stringent endpoint of complete response also did not show an advantage for the MMF arm.…”

“…Case-series reports and phase 2 studies have suggested that MMF might be effective for treatment of steroidrefractory chronic GVHD both in adults and in children. [6][7][8][9][10][11][12][13][14][15] In 2 large surveys, respondents endorsed MMF more frequently than other agents for treatment of high-risk or steroid-refractory chronic GVHD. 16,17 These results suggested that outcomes among patients with chronic GVHD might be improved by adding MMF to the initial systemic treatment regimen.…”

Combination antithymocyte globulin and soluble TNFα inhibitor (etanercept) +/− mycophenolate mofetil for treatment of steroid refractory acute graft-versus-host disease

“…The first involves use of cytotoxic agents directed towards effector (T) cells, with agents such as antithymocyte globulin (ATG), OKT3 or mycophenolate mofetil (MMF). [2][3][4][5][6] The second approach is based upon blockage of cytokine pathways involved in the pathogenesis of acute GVHD, by use of antibodies inhibiting especially tumor necrosis factor-a (TNFa) (etanercept, infliximab) and interleukin-2 (dacluzimab, basiliximab) pathways. [7][8][9][10][11][12][13][14][15][16][17] We have previously reported on use of tacrolimus and ATG for steroid refractory acute GVHD.…”