Impact of Posttransplant Cyclophosphamide-Based GVHD Prophylaxis in Patients 70 Years and Older: An Update from BMT CTN 1703

Researchers from the BMT CTN reported that posttransplant cyclophosphamide-based GVHD prophylaxis significantly improves outcomes for adults aged 70 years and older undergoing allo-HCT.

Researchers from the Blood and Marrow Transplant Clinical Trials Network (BMT CTN) reported that posttransplant cyclophosphamide (PTCy)-based GVHD prophylaxis significantly improves outcomes for adults aged 70 years and older undergoing allogeneic hematopoietic cell transplantation (allo-HCT). Their findings, published in Blood Advances, come from a subgroup analysis of the phase III BMT CTN 1703 trial (NCT03959241), which compared PTCy with the conventional tacrolimus/methotrexate (Tac/MTX) regimen after reduced-intensity conditioning. Of the 431 patients enrolled in the study, 96 were aged ≥ 70 years. Despite concerns that older adults experience higher treatment-related toxicity and graft-versus-host disease (GVHD), PTCy prophylaxis produced markedly better results.

Historically, concerns over regimen-related toxicity, higher rates of GVHD, and increased nonrelapse mortality have limited the use of transplant in this age group. Investigators sought to determine whether the benefits of PTCy observed in the overall BMT CTN 1703 trial extended to this vulnerable subgroup. Results showed that PTCy not only improved disease control but also enhanced survival outcomes. Adjusted 1-year overall survival (OS) was 94.3% with PTCy versus 60.2% with Tac/MTX (HR = 0.08; p = .001). The 1-year graft-versus-host disease–free, relapse-free survival (GRFS) rate reached 67.1% with PTCy compared to only 29.5% with Tac/MTX (HR = 0.27; p < .001). Nonrelapse mortality was significantly lower with PTCy, 4.7% compared with 19.4% (HR = 0.19; p = .04), while relapse or progression was also reduced (14.3% vs 29.3%; HR = 0.30; p = .03). These findings translated into superior relapse-free survival (80.5% vs 50.3%) and GVHD-free survival (75.8% vs 41.0%). Importantly, no cases of grade 3–4 acute GVHD were observed in PTCy-treated patients compared with nearly 10% incidence in the Tac/MTX group.

Engraftment, infection incidence, and organ toxicity rates were broadly comparable between treatment arms, though platelet recovery was somewhat delayed with PTCy. Patient-reported outcomes showed that symptom burden remained stable among PTCy recipients, in contrast to worsening symptoms among Tac/MTX recipients over the first posttransplant year. Collectively, these data establish PTCy as the optimal GVHD prophylaxis strategy for adults ≥ 70 years. By reducing toxicity, minimizing relapse, and markedly improving survival outcomes, PTCy expands the therapeutic window for curative transplantation and supports broader use of allo-HCT in older adults, a population historically excluded from this potentially life-saving therapy.

Reference

Abedin SM, Martens MJ, Bolaños-Meade J, et al. Impact of Post-Transplant Cyclophosphamide-Based GVHD Prophylaxis in Patients 70 years and Older: An Update from BMT CTN 1703. Blood Adv. Published online April 30, 2025.

doi.10.1182/bloodadvances.2025015964

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