The phase 2 ACCESS trial has achieved its primary endpoint, demonstrating promising survival outcomes for patients receiving post-transplant cyclophosphamide (PTCy) as graft-versus-host disease (GVHD) prophylaxis in HLA-mismatched unrelated donor transplants.
The study, conducted in patients with hematologic malignancies, reported an impressive one-year overall survival rate of 84% among recipients of mismatched unrelated donor (MMUD) peripheral blood stem cell transplantation with PTCy prophylaxis. This marks a significant improvement from the previously reported 72% survival rate in the phase 2 15-UUMD trial.
Enhanced Survival Outcomes
The ACCESS trial (NCT04904588) showed notable progress in GVHD-free, relapse-free survival, achieving a rate of 48% compared to 38% in the earlier 15-UUMD study. Importantly, researchers observed comparable survival and GVHD outcomes regardless of whether patients had single or multiple HLA mismatches.
Clinical Implications and Treatment Strategy
Dr. Jeffery J. Auletta, Chief Scientific Director at the Center for International Blood and Marrow Transplant Research, emphasized the significance of these findings, particularly given that peripheral blood stem cells represent the most common transplant source. The study's success opens new possibilities for expanding myeloablative conditioning to a broader patient population.
"By leveraging myeloablative conditioning in combination with MMUD transplantation, high-dose chemotherapy can also provide a graft-vs-leukemia effect to enhance disease control," explained Dr. Auletta. This dual-action approach combines chemotherapeutic and immune-mediated mechanisms to eliminate malignant cells while establishing donor-derived immunity.
Treatment Protocol
The trial utilized myeloablative conditioning followed by peripheral blood stem cell transplantation, with PTCy administered as GVHD prophylaxis. This protocol demonstrates the feasibility of performing successful transplants even in cases with multiple HLA mismatches, potentially expanding the donor pool for patients requiring stem cell transplantation.
