BMT Tandem Meetings | Mycophenolate mofetil comparison to methotrexate for GvHD prophylaxis

The Center for International Blood and Marrow Transplant Research (CIBMTR) database was used to compare the efficacy of graft-versus-host disease prophylaxis combination therapy using mycophenolate mofetil or methotrexate, in addition to a calcineurin inhibitor. Outcomes data was presented by Saurabh Chhabra  from Medical College of Wisconsin, Milwaukee, WI, on February 21 at the 2018 BMT Tandem Meeting in Salt Lake City, Utah.  

Patients were divided into eight study cohorts of treatment regimens for matched unrelated donor (MUD) and sibling donor (SD) transplants. The therapy groups were as follows: methotrexate-tacrolimus (MTX-Tac), methotrexate-cyclosporine (MTX-CSP), mycophenolate-tacrolimus (MMF-Tac), mycophenolate-cyclosporine (MMF-CSP). The median follow-up time was 48 to 71 months in the eight cohorts.

Key Findings:

• N = 1584 adults total
• Sibling donors
  • MMF + CSP risk grade II-IV acute GVHD (aGVHD), HR = 1.62 (95% CI, 1.07–2.45), P = 0.02
  • Addition of anti-thymocyte globulin (ATG) relative risk (RR) cGVHD = 0.55, P = 0.001
  • No differences in the 4 cohorts for grade III-IV aGVHD, chronic GVHD (cGVHD), overall survival (OS), disease-free survival (DFS) or non-relapse mortality (NRM)
• Matched unrelated donors
  • MMF + CSP risk grade II-IV aGvHD, HR = 1.78 (95% CI, 1.33–2.38), P = <0.001
  • MMF + Tac risk grade II-IV aGvHD, HR = 1.33 (95% CI, 1.03–1.71), P = 0.03
  • MMF +CSP risk grade III-IV aGvHD, HR = 1.93 (95% CI, 1.21–3.08), P = 0.006
  • MMF + TAC risk grade III-IV aGVHD, HR = 1.55 (95% CI, 1.05–2.29), P = 0.03
  • Addition of ATG RR cGvHD, HR = 0.74, P = 0.03
  • There were no differences in the 4 cohorts for cGvHD, OS, DFS, or NRM
  • Risk of relapse in MMF+ CSP and MMF + Tac groups was lower compared to MTX-Tac

The findings of this large CIBMTR study demonstrated MMF in combination with a calcineurin inhibitor was inferior in terms of aGvHD prophylaxis in matched unrelated donor transplants. In the unrelated donor group, there was however an advantage in terms of disease relapse. This data is useful for predicting impact on aGvHD while understanding MMF therapies do not have a negative impact on patient survival.