The Effect of Mycophenolate Mofetil Dose per Kilogram on Clinical Outcomes of Allogeneic Hematopoietic Cell Transplant with Post-Transplant Cyclophosphamide.

Mycophenolate mofetil (MMF) dose/kg can influence clinical outcomes of allogeneic hematopoietic cell transplantation (HCT) including acute graft-versus-host disease (GVHD) (Harnicar BBMT 2015; Bejanyan BBMT 2018). When used for GVHD prophylaxis in conjunction with post-transplant cyclophosphamide (PTCy), MMF is generally dosed at 15 mg/kg three times daily (capped at a maximum of 3 g/day) and combined with either tacrolimus or sirolimus. Thus, many adults receive the maximum dose and a variable dose/kg of MMF. We sought to investigate the impact of MMF dose/kg on clinical outcomes of HCT in the setting of PTCy-based GVHD prophylaxis, where the effect of MMF dose/kg is unknown. Included are 112 consecutive adult patients with hematologic malignancies who received myeloablative (n=70) or reduced intensity (n=42) HCT at the Moffitt Cancer Center between 2012-2018 with T-cell replete peripheral blood stem cells (n=94) or bone marrow (n=18). GVHD prophylaxis consisted of PTCy/MMF and either tacrolimus (n=57) or sirolimus (n=55). MMF dose relative to patient actual body weight (mg/kg/day), was stratified by tertiles into low (<30 mg/kg/day, n=31), intermediate (30-40 mg/kg/day, n=45) and high (>40 mg/kg/day, n=36). The median age at transplant was 57.8 (range: 21-75) years. Median follow-up was 12 months (range: 0.3-39). Donors were haploidentical related (n=74), mismatched unrelated (n=26), and matched related/unrelated (n=12). MMF dose groups had similar characteristics, except the low dose group having a higher proportion of males (p<0.01), higher body mass index (p<0.01), and patients receiving <3g/day MMF (p<0.01). Cumulative incidence rate (CIR) of neutrophil engraftment was 96% and of platelet engraftment was 89% for all patients. For the entire cohort, CIR was 41% for grade II-IV and 11% for grade III-IV acute GVHD at day 100 and 46% for chronic GVHD at 2-years. MMF dose had no significant effect on acute (Figure 1) or chronic GVHD (Table). Probability of 2-year non-relapse mortality (NRM) was 17% and relapse was 31% for all patients. Corresponding 2-year overall survival (OS) was 60% and disease-free survival (DFS) was 52% (Figure 2). While MMF dose did not significantly influence NRM, relapse or OS, we observed significantly better DFS in patients receiving intermediate vs. low weight-based MMF dose (HR=0.5, CI: 0.25-0.998, p=0.049). In patients receiving PTCy based GVHD prophylaxis, MMF dose/kg had no significant effect on GVHD. However, lower MMF dose/kg was associated with worse DFS. This study suggests that <30 mg/kg/day may lead to inferior clinical outcomes. Larger studies are needed to confirm these findings. [ABSTRACT FROM AUTHOR]