Impact of Reduced Duration of Mycophenolate Mofeitl (MMF) Is Associated with Reduced 12 Month Overall Survival (OS) without an Impact on the GVHD and Disease Relapse

Post-transplant cyclophosphamide (PTCy) with immunosuppressive agents is increasingly adopted for GVHD prophylaxis. Mycophenolate mofetil (MMF) is traditionally combined with PTCy and Tacrolimus for its immunosuppressive effects and presumed anti-tumor and anti-infective benefits, but is limited by gastrointestinal and myelosuppressive toxicities. At our institution, MMF exposure has been capped at 28 days, with earlier physician-directed discontinuation based on tolerance and count recovery. We retrospectively evaluated 135 allogeneic transplant patients receiving PTCy/Tacrolimus. Patients were stratified by MMF exposure: ≤20 days (‘MMF-L’, n=38; median 17 days) vs ≥21 days (‘MMF-M’, n=97; median 24 days). No patient received >28 days of MMF. Neutrophil engraftment occurred at a median of 16 days in both groups, while platelet engraftment was faster in MMF-L (25 vs 31 days). One-year PFS was 87% (MMF-L) vs 84% (MMF-M). One-year OS was lower in MMF-L (79% vs 91%) due to higher TRM (20% vs 5%). Rates of grade III–IV aGVHD and chronic GVHD were similar between the 2 cohorts. On multivariate analysis, MMF exposure ≤21 days was independently associated with inferior OS. In summary, abbreviated MMF exposure with PTCy/Tac reduced relapse but was associated with increased TRM and lower OS at 12 months. Further analysis needs to be performed to elucidate the causes of increased TRM but perhaps the decision to lower MMF exposure may have been due to inherently higher-risk status of these patients skewing the outcomes towards a worse TRM. Prospective randomized studies are needed to confirm these findings and optimize MMF treatment duration.