Comparison of Sirolimus and Mycophenolate Mofetil As Salvage Treatment for Acute Graft-Versus-Host Disease

Abstract 4548

Acute graft vs. host disease (aGVHD) refractory or dependent on glucocorticoid therapy is a major source of mortality following allogeneic hematopoietic cell transplantation (HCT). Comparative studies to evaluate the efficacy of available salvage immune suppressive agents are lacking. We retrospectively compared the efficacy of sirolimus (SIR) and mycophenolate mofetil (MMF) as salvage aGVHD therapy for glucocorticoid refractory, dependent or intolerant patients. Of 281 consecutive patients who received HCT at Moffitt Cancer Center from 07/2004 to 09/2009, we identified 84 patients who received tacrolimus/methotrexate (Tac/MTX) as GVHD prophylaxis, were treated with systemic glucocorticoids as first line therapy for acute GVHD grades 2–4, were refractory (n=72) or dependent (n=12) to glucocorticoids, and received second line GVHD treatment with MMF (n=56) or SIR (n=28). Patient demographics and treatment variables were similar between the two groups except for year of transplant, which was earlier for MMF. Median age of the entire group was 50 (range 17 – 68). Disease diagnoses included AML (n=27), NHL (n=14), MDS (n=12), ALL (n=9), CML (n=7), CLL (n=4), SAA (n=2), MPD (n=5), MM/PCL (n=3), and HL (n=1). Conditioning regimens were busulfan/fludarabine for 71, and other regimens for 13. Except for 1 bone marrow graft in each group, all received peripheral blood stem cells. Graft sources were from HLA-matched siblings (35), or 8/8 HLA-matched unrelated donors (49). Overall grade distribution of aGVHD at time of salvage for MMF vs. SIR was the following: grade 1 (13 vs. 2), grade 2 (31 vs. 16), grade 3 (9 vs. 5) and grade 4 (3 vs. 5). Median steroid dose at the time of salvage was 1 (range 0.17 – 2.28) mg/kg for MMF group and 1 (range 0.12 – 2.0) mg/kg for SIR group. Median time from steroid to salvage was 20 (range 1 – 208) days for MMF and 19 (range 1 – 275) days for SIR (p=0.84). Complete response (CR) rates following initiation of MMF or SIR did not significantly differ at the following time points: 1 week (MMF 30%, SIR 21%), 4 weeks (MMF 44%, SIR 46%), and 6 weeks (MMF 60%, SIR 58%). Overall response rates (ORR) also did not differ significantly: 1 week (MMF 57%, SIR 42%), 4 weeks (MMF 57%, SIR 77%), and 6 weeks (MMF 72%, SIR 75%). Flare or progression of aGVHD while on salvage regimen was noted in 50% (MMF) and 36% (SIR) of patients (p=0.64). Median overall survival from the time of salvage therapy for MMF vs. SIR did not significantly differ, 11.6 (95% CI 7.0 – 28.1) vs. 9.7 (95% CI 5.4 – 15.9) months, log-rank p = 0.88. These retrospective data suggest that MMF and SIR have comparable activity in the treatment of steroid refractory or dependent acute GVHD.