Post-Transplant Cyclophosphamide-Based Graft-Versus-Host Disease Prophylaxis After Mismatched Unrelated Donor Peripheral Blood Stem Cell Transplantation
Mené sur 145 patients atteints d'un cancer hématologique de stade avancé, cet essai multicentrique non randomisé de phase II évalue l'intérêt, pour réduire le risque de maladie du greffon contre l'hôte (GVHD), et l'efficacité, du point de vue de la survie globale à 1 an, d'une prophylaxie par cyclophosphamide après une greffe de cellules souches de sang périphérique d'un donneur non apparenté
Purpose: Allogeneic hematopoietic stem cell transplantation (HSCT) is a curative treatment for advanced hematologic malignancies. HSCT using human leukocyte antigen (HLA)-mismatched donors is historically associated with inferior survival. Patients from underrepresented racial and ethnic groups more frequently rely on HLA-mismatched donors. We hypothesized that post-transplant cyclophosphamide (PTCy) based graft versus host disease (GVHD) prophylaxis would improve outcomes for HSCT recipients using peripheral blood stem cells (PBSCs) from HLA-mismatched unrelated donors (MMUDs) by reducing the risk of GVHD.
Methods: This phase II, nonrandomized, multicenter trial assessed PBSCs in the setting of a GVHD prophylaxis regimen of cyclophosphamide, tacrolimus, and mycophenolate mofetil in two adult strata: myeloablative conditioning (MAC) and reduced-intensity or nonmyeloablative (RIC/NMA) conditioning before HSCT from a MMUD. The primary objective was to estimate 1 year overall survival (OS) for each stratum. Key secondary end points included incidences of acute and chronic GVHD.
Results: A total of 145 patients enrolled, with 59% self-identifying within an underrepresented group. The 1 year OS was 83.8% (95% CI, 73.1% to 90.4%) for MAC and 78.6% (95% CI, 67% to 86.5%) for RIC/NMA. Incidences of grades III to IV acute GVHD at 6 months were 8% (95% CI, 3.2 to 15.6) for MAC and 10% (95% CI, 4.4 to 18.4) for RIC/NMA. Moderate/severe chronic GVHD at 1 year was 10.3% (95% CI, 4.4 to 18.9) for MAC and 8.6% (95% CI, 3.5 to 16.6) for RIC/NMA. 32% of patients whose donors matched at fewer than seven of eight HLA alleles had similar OS compared with those with donor matched at seven of eight alleles.
Conclusion: PTCy-based GVHD prophylaxis after MMUD HSCT with PBSC grafts results in favorable 1 year OS. Using MMUDs expands donor availability to all patients regardless of ancestry (ACCESS; ClinicalTrials.gov identifier: NCT04904588).
Journal of Clinical Oncology , article en libre accès, 2025