Trio of Posttransplant Cyclophosphamide, Tacrolimus, Mycophenolate Mofetil Efficacious for GVHD Prophylaxis in 8/8- and 7/8-Matched Donors

By Dustin Samples - Last Updated: February 15, 2023

Numerous immunosuppressing drugs are available for graft-versus-host disease (GVHD) prophylaxis. Common among them are the calcineurin inhibitor cyclosporine, the chemotherapy agent methotrexate, and the macrolide lactone tacrolimus. Generally, 1 or more of these and other agents are used to prevent GVHD in patients undergoing allogeneic hematopoietic cell transplantation (HCT).

In a phase II trial from the University of Minnesota, Dr. Shernan Grace Holtan and colleagues hypothesized that the combination of posttransplant cyclophosphamide (PTCy), tacrolimus, and mycophenolate mofetil (MMF) would result in a lower incidence of GVHD in patients undergoing HCT from matched or single antigen mismatched donors than their previously used combination of cyclosporine and methotrexate for GVHD prophylaxis.

In this study, Dr. Holtan et al recruited and treated 125 adult and pediatric patients (median follow-up, 472 days). They demonstrated no incidence of grade IV acute GVHD, 4% incidence of grade III-IV acute GVHD, and 16% incidence of grade II-IV acute GVHD. Furthermore, in their cohort, there were no deaths attributed to GVHD.

Only 3 patients developed chronic GVHD requiring immune suppression.

Compared to their previous dual-drug prophylaxis for GVHD with cyclosporine and methotrexate, prophylaxis with the combination of PTCy, MMF, and tacrolimus led to higher overall survival at 2 years (80%), as well as higher GVHD relapse-free survival (57%). In addition, using this trio, grade II-IV acute GVHD, chronic GVHD, and non-relapse mortality were all lower compared to the previous regimen of cyclosporine/methotrexate.

Survival outcomes were not significantly different between those who received an 8/8 matched transplant and those who received a 7/8 matched transplant.

“Myeloablative HCT with PTCy/Tac/MMF results in extremely low incidence of severe acute and chronic GVHD…Relapse risk is not increased compared to our historical [cyclosporine/methotrexate] cohort,” concluded Dr. Holtan.

Holtan SG, Hoover A, O’Leary D, et al. Phase II study of myeloablative 8/8- or 7/8-matched allotransplantation with post-transplant cyclophosphamide, tacrolimus, and mycophenolate mofetil: marked reduction in GVHD risk without increase relapse risk compared to historical cyclosporine/methotrexate. Abstract #34. Presented at the 2023 Tandem Meetings of ASTCT and CIBMTR; February 15-19, 2023; Orlando, FL.

Post Tags:TCT Meeting 2023
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