Inferior Outcomes with Cyclosporine and Mycophenolate mofetil after Myeloablative Allogeneic Hematopoietic Cell Transplantation

Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation. 2019
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Abstract

The combination of a calcineurin inhibitor (cyclosporine [CSA] or tacrolimus [Tac]) and methotrexate (MTX) or mycophenolate mofetil (MMF) are widely used approaches to graft-versus-host disease (GVHD) prevention. There is limited and conflicting data, however, on the comparative effectiveness of MMF compared to MTX. We analyzed data from the CIBMTR for adult patients undergoing first myeloablative hematopoietic cell transplant (HCT) from an HLA-identical matched related (MRD) (N=3979) or matched unrelated donor (URD) (N=4163) using CSA+MMF, CSA+MTX, Tac+MMF or Tac+MTX for GVHD prevention from 2000-2013. Within the MRD cohort, 2252 received CSA+MTX, 1391 Tac+MTX, 114 CSA+MMF, and 222 Tac+MMF. Recipients of CSA+MMF had a higher incidence of acute grade 2-4 (HR 1.65, 95% CI 1.24-2.20, P<0.001) and grade 3-4 (HR 1.92, 95% CI 1.31-2.83, P<0.001) GVHD compared to Tac+MTX. The use of CSA+MMF was also associated with inferior overall survival (OS) (HR 2.31, 95% CI 1.73-3.09, P<0.001) due to higher transplant-related mortality (TRM) (HR 4.03, 95% CI 2.61-6.23, P<0.001) versus Tac+MTX. Within the URD cohort, 974 received CSA+MTX, 2697 Tac+MTX, 68 CSA+MMF, and 424 Tac+MMF. CSA+MMF was again significantly associated with a higher incidence of grade 3-4 acute GVHD (HR 2.31, 95% CI 1.57-3.42, P<0001), worse OS (HR 2.36, 95% CI 1.67-3.35, P<0.001), and higher TRM (HR 3.09, 95% CI 2.00-4.77, P<0.001), compared to Tac+MTX, and other regimens. This large retrospective comparison of MMF versus MTX in combination with CSA or Tac thus demonstrates significantly worse GVHD and survival outcomes with CSA+MMF compared to Tac+MTX.

PICO Summary

Population

Adult patients undergoing first myeloablative haematopoietic cell transplant from an HLA-identical matched related donor (n=3979) or matched unrelated donor (n=4163)

Intervention

Matched Related Donor cohort: CSA+MMF (n=114) or 222 Tac+MMF (n=222); Unrelated Donor cohort: CSA+MMF (n=68) or Tac+MMF (n=424)

Comparison

Matched Related Donor cohort: CSA+MTX (n=2252) or Tac+MTX (n=1391); Unrelated Donor cohort: CSA+MTX (n=974) or 2697 Tac+MTX (n=2697)

Outcome

In the Matched Related Donor cohort, recipients of CSA+MMF had a higher incidence of acute grade 2-4 and grade 3-4 GVHD compared to Tac+MTX. The use of CSA+MMF was also associated with inferior overall survival due to higher transplant-related mortality versus Tac+MTX. In the Unrelated Donor cohort, CSA+MMF was again significantly associated with a higher incidence of grade 3-4 acute GVHD, worse overall survival, and higher treatment related mortality, compared to Tac+MTX, and other regimens.

Study details

Study Design : Based on Registry Data
Treatment : GvHD Prophylaxis
Language : eng
Credits : Bibliographic data from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine