ALLG BM12 CAST: improved GRFS through novel GVHD prophylaxis

Graft-versus-host-disease (GVHD) prophylaxis with cyclophosphamide and cyclosporin yielded positive outcomes in patients with acute leukaemia or myelodysplastic neoplasm (MDS) who underwent matched sibling donor peripheral blood stem cell (PBSC) transplantation.

The phase 3 ALLG BM12 CAST trial (ACTRN12618000505202) recruited 134 participants with acute leukaemia or myelodysplastic neoplasm who underwent myeloablative or reduced intensity conditioning allogeneic PBSC transplantation from a matched sibling donor 1:1 to cyclosporin plus methotrexate or to cyclosporin plus post-transplant cyclophosphamide (PTCy). It was hypothesised that the latter regimen would outperform the first regimen as prophylactic treatment for GVHD. The primary endpoint was GVHD-free and relapse-free survival (GRFS), and Dr David Curtis (Alfred Health, Melbourne, Australia) presented the findings [1].

Grade 3 or 4 acute GVHD (19% vs 6%; P=0.032) and moderate to severe chronic GVHD (34% vs 17%; P=0.033) were more common in the methotrexate arm than in the PTCy arm. Next to that, the 3-year GRFS rates were 14% and 49% (HR 0.42; 95% CI 0.27-0.66; P<0.001; See Figure), in favour of the experimental arm. Dr Curtis added that the death rates were comparable, with 6% in both arms, but that ‘being event-free’ was more often reached by patients in the PTCy arm (47% vs 18%).

Figure: Graft-versus-host disease-free relapse-free survival (GRFS) [1]



cGVHD, chronic graft-versus-host disease; aGVHD, acute graft-versus-host disease; CsA, cyclosporine A; MTX, methotrexate; PTCy, post-transplant cyclophosphamide; SCT, stem cell transplantation; GRFS, graft-versus-host disease–free, relapse-free survival; CI, confidence interval; HR, hazard ratio; p, p-value; No SCT, no stem cell transplantation.

“Delayed platelet engraftment was the only early toxicity we noticed,” mentioned Dr Curtis. Furthermore, grade 3 or higher adverse event rates in the first 100 days were 33% for participants on methotrexate and 20% for participants on PTCy. The 2-year overall survival (OS) rates were 71% and 83%, numerically but not significantly in favour of the experimental arm (HR 0.59; 95% CI 0.29-1.19; P=0.132). “Although the novel treatment did not significantly improve OS, we did see a favourable effect on relapse-free survival (HR 0.55; 95% CI 0.30-1.00; P=0.045).

“The PTCy-regimen outperformed the methotrexate-regimen concerning GRFS in participants who underwent matched sibling PBSC transplantation, without increasing relapse or early toxicity,” Dr Curtis concluded.

1. Curtis D, et al. A phase 3 randomised trial of post-transplant cyclophosphamide for GVHD prophylaxis in matched sibling donor peripheral blood stem cell transplantation: the ALLG BM12 CAST trial. S103, EHA2025 Congress, 12–15 June, Milan, Italy.

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Posted on 2 September 2025