Mycophenolate Mofetil Is Effective and Well Tolerated in the Treatment of Refractory Acute and Chronic Graft-versus-Host Disease

Abstract

We enrolled 11 patients with refractory graft-versus-host disease (GVHD) in a prospective trial evaluating the efficacy of mycophenolate mofetil (MMF). Four (67%) of the 6 patients with acute GVHD and all 5 patients with chronic GVHD responded to MMF. Ten (91%) of the 11 patients were able to decrease steroid use (median decrease, 86%; range, 25%-100%). After a median follow-up of 18 months (range, 1-65 months), 7 patients (64%) remained alive. The adverse events were infectious complications (36%), diarrhea (27%), and neutropenia (18%); the only patient discontinuing MMF did so because of grade 4 neutropenia. This preliminary study suggests that MMF is a well-tolerated agent and has a beneficial effect in the treatment of refractory acute and chronic GVHD.

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

“…[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.…”

Mycophenolate mofetil for the management of steroid-refractory acute graft vs host disease

“…[31][32][33][36][37][38] Direct comparisons to other series examining MMF in refractory GVHD are difficult for several reasons. Basara et al reported an overall grade improvement in 65% of patients, where MMF was used as first-line therapy in addition to CSA and prednisolone on development of aGVHD or cGHVD.…”

Prophylactic and therapeutic treatment of graft-versus-host disease in Japan

“…The nationwide survey of ATG as second-line therapy for acute GVHD is ongoing. Takami et al [129] evaluated the outcomes of patients who were treated with MMF at a dosage of 1500 mg/ day in a prospective study. Onishi et al [130] retrospectively analyzed the outcome of patients who received MMF at an initial dose of 500-3000 (median 1500) mg/day.…”