Fludarabine and total body irradiation 800 cgy or 1125 cgy for allogeneic stem cell transplant using graft versus host disease prophylaxis with post-transplant cyclophosphamide and tacrolimus, without mycophenolate mofetil (OmitMMF trial)

Abstract Background: Mycophenolate mofetil (MMF) has been a standard adjunct of the post-transplant cyclophosphamide (PTCy) graft versus host disease (GVHD) prophylaxis regimen since it was introduced in patients receiving haploidentical transplants following non-myeloablative conditioning therapy. Objectives: Evaluate the safety and potential benefits of eliminating MMF in patients receiving reduced-intensity (RI) and myeloablative (MA) conditioning with fludarabine and total body irradiation (FluTBI) prior to peripheral blood stem cell transplantation from matched or haploidentical related, or unrelated, donors. Study Design: Open label phase 2 study with early stopping rules for or grade III-IV acute GVHD (aGVHD) >20%, engraftment failure >10%, or non-relapse mortality (NRM) > 10%. Outcomes of 60 evaluable patients were compared to matched historical control patients. Results: The median time to neutrophil engraftment was not different for OmitMMF patients (16 days) than matched control patients (15 days; p = 0.31). The median time to platelet engraftment was the same for OmitMMF patients (21 days) and matched controls (21 days). One OmitMMF patient had graft rejection, attributed to poor graft viability. The rate of grade III-IV aGVHD was low for both OmitMMF patients (0%) and control patients (1.7%; p = 0.31). Grade II-IV aGVHD was similar for OmitMMF patients (22%) and controls (12%), but subgroup analysis revealed that the rate of grade II-IV aGVHD was significantly higher in OmitMMF patients who received MA conditioning than the control group who received the same regimen (p = 0.024). However, this did not translate to a higher risk of cGVHD in OmitMMF pts as a whole (p = 0.98), or in those receiving MA conditioning (p = 0.46) compared to matched controls. NRM was very low (3.3%) for both groups. Relapse by 1 year was not different in OmitMMF patients (10%) and control patients (13%; p =0.54). One year overall survival was also similar for OmitMMF (97%) and control (93%) patients (p = 0.41). GVHD-free, relapse-free survival was 87% in OmitMMF patients and 83% in matched controls (p = 0.58). The rate of CMV, EBV or polyoma BK virus reactivation also was not different in OmitMMF subjects and controls. Conclusions:MMF can be safely eliminated in patients receiving RI and MA FluTBI conditioning regimens and PTCy/tacrolimus GVHD prophylaxis. A higher rate of grade II-IV aGVHD was observed in patients receiving MA TBI, but this did not adversely any other outcome measures.