Work

Omitmmf: Graft Versus Host Disease Prophylaxis with Post-Transplant Cyclophosphamide and Tacrolimus, without Mycophenolate Mofetil, Following Conditioning with Fludarabine and Total Body Irradiation 800 or 1125 Cgy

Year: 2025

Type: article

Abstract: Introduction Mycophenolate mofetil (MMF) has been incorporated into allogeneic transplant regimens to reduce the risk of acute graft versus host disease (aGVHD) and to decrease the risk of graft rejection when conditioning therapy is non-myeloablative. We hypothesized that eliminating MMF from our routine GVHD prophylactic regimen of post-transplant cyclosphosphamide (PTCy), tacrolimus (tacro) and MMF might expedite hematopoietic recovery and immune reconstitution without increasing the risk of graft rejection or aGVHD. Objective To evaluate the safety and potential clinical benefits of eliminating MMF from GVHD prophylaxis. Methods This open label safety study enrolled 60 allogeneic stem cell patients undergoing their first transplant for any diagnosis other than myelofibrosis. All subjects underwent conditioning with FluTBI-800 cGy or FluTBI-1225 cGy followed by infusion of ≥3 × 10 6 CD34 peripheral blood stem cells (PBSC)/kg. All subjects received PTCy/tacro, with tacrolimus tapered off by D+100 in the absence of aGVHD. This study had early stopping rules including graft failure rate of ≥10%, or grade 3-4 aGVHD ≥20%. Secondary endpoints included time to neutrophil and platelet recovery. Spectral flow cytometry using a 40 marker panel was performed on D+30 to evaluate lymphocyte reconstitution. A control group included 60 consecutive allogeneic stem cell transplant patients who underwent transplant preceding the opening of this trial and who would have met all of the entry criteria. Controls all received GVHD prophylaxis with PTCy/tacro, and MMF from D+5 to D+35. Study subjects will be followed for two years post-transplant to evaluate the rate and severity of chronic GVHD, relapse, and overall survival. Results These are the results of all 60 subjects at 100 days. Only one graft rejection occurred, deemed not related to study procedures (poor graft viability from outside collection facility), and only one subject developed grade 3-4 aGVHD so no stopping rules were met. Study subjects were well matched to historic controls except the OmitMMF subjects included significantly more haploidentical transplants and fewer matched unrelated donor transplants than the historical controls (p=0.033). Time to neutrophil and platelet recovery were not different from the study group and controls. The incidence of aGVHD was not different in the OmitMMF group than the controls. There was no difference in the incidence of grade 3-4 aGVHD. The OmitMMF subjects had a significantly higher number of CD4+ memory and CD4+CD8+ T-cells with a memory phenotype at Day 30 than controls. Conclusion Eliminating MMF from GVHD prophylaxis following FluTBI conditioning and PBSC transplantation does not appear to increase the risk of graft rejection or the incidence or severity of aGVHD. Ongoing follow up of study subjects will evaluate the rate and severity of chronic GVHD, relapse, and overall survival.

Source: Transplantation and Cellular Therapy

DOI: 10.1016/j.jtct.2025.01.428