Mycophenolate Mofetil Ineffective for Acute Graft-Versus-Host Disease

David Green, MD, PhD

Adding this immunosuppressive agent to prednisone did not improve GVHD survival.

Allogeneic hematopoietic stem-cell transplantation (AHSCT) is often complicated by acute graft-versus-host disease (GVHD) and is generally treated with corticosteroids. Because these agents induce durable remissions in fewer than half of patients with GVHD, they are often combined with immunosuppressive agents. In a previous phase II study, the immunosuppressor mycophenolate mofetil (MMF), when combined with corticosteroids, appeared to improve disease-free interval and overall survival (Blood 2009; 114:511).

To confirm these preliminary results, investigators conducted a phase III trial involving 235 eligible adult and pediatric AHSCT recipients with newly diagnosed acute GVHD. Patients were randomized to receive prednisone with either MMF or placebo. The primary endpoint was GVHD-free survival at day 56 of treatment.

The trial was discontinued because of futility when no significant difference in the primary endpoint was seen between patients receiving MMF or placebo (59.5% and 50.4%, respectively) and the corticosteroid doses at day 28 and 56 did not differ between treatment groups. Patients receiving MMF had a higher incidence of leucopenia (52.7% vs. 34.8%; P=0.01) but similar cumulative incidence of severe infection and similar rates of hospital readmission. In addition, no significant between-group differences were seen in quality of life at day 56 or overall survival at 1 year.

Citation(s):

Bolaños-Meade J et al. Phase 3 clinical trial of steroids/mycophenolate mofetil vs steroids/placebo as therapy for acute GVHD: BMT CTN 0802. Blood 2014 Nov 20; 124:3221.