Novel therapy may replace standard-of-care prophylaxis for GVHD

Post-transplant cyclophosphamide/tacrolimus/mycophenolate mofetil (PTCy/Tac/MMF) outperformed tacrolimus/methotrexate (Tac/MTX) as a prophylaxis for graft-versus-host disease (GVHD) in patients with an indication for reduced-intensity conditioning allogeneic stem cell transplantation (RIC ASCT).

The results of the phase 3 BMT CTN 1703 trial (NCT03959241) were presented by Prof. Shernan Holtan (University of Minnesota, MN, USA) [1]. The study included adult patients receiving RIC ASCT (n=431), who were randomised 1:1 to post-transplant PTCy/Tac/MMF or Tac/MTX. The primary endpoint was the 1-year GVHD-free relapse-free survival (GRFS), a composite endpoint of grade III–IV acute GVHD, chronic GVHD requiring systemic immunosuppression, relapse/progression, or death.

The primary endpoint was met, with a 1-year GRFS of 52.7% in the PTCy/Tac/MMF arm and a 1-year GRFS of 34.9% in the Tac/MTX arm (HR 0.64; P<0.001). The effect was driven by a reduction in grade III–IV acute GVHD (6.3% vs 14.7%, respectively; P=0.001) and a decrease in chronic GVHD requiring systemic immunosuppression (12.5% vs 25%, respectively; P=0.001). Prof. Holtan added that relapse/progression rates were similar, with 20.8% in the PTCy/Tac/MMF arm and 20.2% in the Tac/MTX arm (P=0.906; see Figure).

Figure: Improved GVHD outcomes not at expense of relapse [1]



GVHD, graft-versus-host disease; PTCy/Tac/MMF, post-transplant cyclophosphamide/tacrolimus/mycophenolate mofetil; Tac/MTX, tacrolimus/methotrexate.

There were more grade 2–3 infections in the experimental arm (40.0% vs 30.4; P=0.018), mostly explained by an increased rate of grade 2 infections. Also, fewer patients in the experimental arm achieved an absolute lymphocyte count >1,000 (53.8% vs 63.2%; P<0.001). Finally, after 1 year of follow-up, it appeared that patients in the Tac/MTX arm were more likely to die from acute GVHD (14.3% vs 4.2%), whereas patients in the PTCy/Tac/MMF arm were more likely to die from organ failure (22.9% vs 10.7%).

The authors concluded that PTCy/Tac/MMF should become the standard-of-care GVHD prophylaxis in adults receiving RIC ASCT.

1. Holtan S, et al. BMT CTN 1703: A randomized, Multicenter, Phase III Trial of Tacrolimus/Methotrexate versus Post-Transplant Cyclophosphamide/Tacrolimus/Mycophenolate Mofetil in Non-Myeloablative/Reduced Intensity Conditioning Allogeneic Peripheral Blood Stem Cell Transplantation. Late-Breaking Abstract 4, ASH 64^th Annual Meeting, 10–13 December 2022, New Orleans, LA, USA.

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Posted on 20 February 2023