Dr Jimenez Jimenez on PBSC from HLA-Mismatched Donors in Hematological Malignancies

Antonio Martin Jimenez Jimenez, MD, associate professor, medicine, the University of Miami Sylvester Comprehensive Cancer Center, discusses findings from the phase 2 ACCESS study (NCT04904588), which evaluated reduced-intensity conditioning therapy, mobilized peripheral blood stem cells (PBSC) from HLA-mismatched unrelated donors (MMUD) and post-transplant cyclophosphamide (PTCy) for graft-vs-host disease (GVHD) prophylaxis in adult patients with hematological malignancies. This study builds on previous data from the multicenter phase 2 15-MMUD trial (NCT02793544).

The primary aim of ACCESS was to determine whether the 1-year overall survival (OS) rate with mobilized PBSC would be comparable with that observed with bone marrow grafts, Jimenez Jimenez says. The results demonstrated an OS rate of 79% (95% CI, 68%-87%) at 1 year post-HCT, which is comparable with the OS rates seen in patients receiving fully matched grafts and consistent with the outcomes in the PTCy arm of the phase 3 BMT CTN 1703 study (NCT03959241), Jimenez Jimenez notes. This OS rate highlights the efficacy of using PBSC from MMUD in the reduced-intensity conditioning setting with PTCy-based GVHD prophylaxis.

Other key outcomes included a GVHD relapse-free survival rate of 51% (95% CI, 39%-62%) at 1 year, indicating that over half of the patients were alive, disease free, and without significant GVHD-related complications at that time point, Jimenez Jimenez explains. This outcome is particularly noteworthy given the use of mismatched grafts, Jimenez Jimenez emphasizes. Additionally, the non-relapse mortality rate with mobilized PBSC was deemed acceptable, reinforcing the safety profile of this approach, according to Jimenez Jimenez.

The estimated incidence of grade 3/4 acute GVHD at 6 months was 9% (95% CI, 3%-16%), and severe chronic GVHD was reported in an estimated 9% (3%-17%) of patients at 1 year. This low rate of severe GVHD underscores the effectiveness of PTCy-based prophylaxis in managing GVHD in this patient population, Jimenez Jimenez states.

In a presentation given at the 2024 ASCO Annual Meeting, Jimenez Jimenez emphasized that these findings indicate that mobilized PBSC from MMUD, combined with PTCy-based GVHD prophylaxis, offers a viable alternative to bone marrow grafts, providing comparable survival outcomes and a favorable safety profile. The ACCESS study supports the use of mobilized PBSC in this setting, potentially expanding the donor pool for patients requiring allogeneic stem cell transplantation.