Post-Transplant Cyclophosphamide, Tacrolimus, and Mycophenolate Mofetil for GVHD Prophylaxis in Reduced Intensity Conditioning

Results from the Phase 3 BMT CTN 1703 Study

Shernan G Holtan, MD, University of Minnesota, Minneapolis, MN, discusses the findings from the phase 3 BMT CTN 1703 trial, which she presented at the 2022 American Society of Hematology (ASH) Annual Meeting & Exposition in New Orleans, LA.

The randomized phase 3 Blood and Marrow Transplant Clinical Trials Network (BMT CTN) 1703 study compared a 3-drug combination of post-transplant cyclophosphamide, tacrolimus, and mycophenolate mofetil (MMF) with the standard of care (tacrolimus plus methotrexate) for graft-versus-host-disease (GVHD) prophylaxis for patients undergoing reduced intensity conditioning allogeneic hematopoietic cell transplantation (alloHCT).

BMT CTN 1703 met its primary endpoint of GVHD/relapse or progression-free survival (GRFS), demonstrating a higher 1-year GRFS with post-transplant cyclophosphamide, tacrolimus, and mycophenolate mofetil compared to the standard of care.  

“[Post-transplant cyclophosphamide, tacrolimus, and mycophenolate mofetil], which has become standard of care for mismatched transplants, should also become the standard of care for GVHD prophylaxis from closely-matched donors receiving reduced intensity conditioning,” Shernan G Holtan, MD, University of Minnesota, Minneapolis, MN, and coauthors wrote.

Transcript:

I'm Shernan Holtan, associate professor of medicine from the University of Minnesota. Recently, I was able to present the results of BMT CTN 1703 at the 2022 ASH Meeting. 

This was a randomized phase 3 study of GVHD prophylaxis in the setting of reduced intensity allogeneic transplantation. The arms of the study were the control arm of tacrolimus methotrexate for GVHD prophylaxis, versus the experimental arm of post-transplant cyclophosphamide, tacrolimus, and MMF. The primary endpoint of the study was 1-year graft-versus-host disease-free, relapse-free survival. Over a couple of years, the study randomized over 400 participants, 1-to-1, to each of the arms.

The main finding was that at 1 year, the experimental arm, post-transplant cyclophosphamide, [tacrolimus] and MMF, had a higher 1-year relapse graft-versus-host-disease-free, relapse-free survival. This was due to a twofold reduction in severe acute graft-versus-host disease, grade 3 to 4, and chronic GVHD requiring systemic immunosuppression. 

Importantly, there was no significant difference in relapse or progression between the arms. So the benefit of this was really driven by the marked reduction in severe acute and chronic graft-versus-host disease.

Based upon these results, we feel that it is now standard of care to give post-transplant cyclophosphamide, tacrolimus and MMF in well-matched reduced intensity peripheral blood stem cell transplants. 

Source:

Holtan S, Hamadani M, WU J, et al. Post-Transplant Cyclophosphamide, Tacrolimus, and Mycophenolate Mofetil As the New Standard for Graft-Versus-Host Disease (GVHD) Prophylaxis in Reduced Intensity Conditioning: Results from Phase III BMT CTN 1703. Presented at the ASH Annual Meeting & Exposition; December 10-13, 2022; New Orleans, LA, and virtual. LBA-4.