Dr Al Malki on Outcomes With PTCy-Based GVHD Prophylaxis in Hematologic Malignancies

Monzr M. Al Malki, MD, associate professor, Division of Leukemia, Department of Hematology & Hematopoietic Cell Transplantation; director, Unrelated Donor BMT Program, Haploidentical Transplant Program, City of Hope, discusses the impact of post-transplant cyclophosphamide (PTCy)–based graft-vs-host disease (GVHD) prophylaxis on survival outcomes following mismatched unrelated donor (MMUD) peripheral blood stem cell (PBSC) transplantation in patients with advanced hematological malignancies, as assessed in the phase 2 ACCESS study (NCT04904588).

The goal of this prospective, multi-center study was to determine whether survival outcomes in adults who underwent PBSC from MMUD would be comparable with those of patients undergoing bone marrow transplant, Al Malki begins. Adult patients were stratified according to whether they received a myeloablative or reduced-intensity conditioning regimen. In the singular pediatric cohort, both conditioning regimens were used.

Results from a planned interim analysis of the first 70 adult patients enrolled onto the reduced-intensity conditioning PBCS cohort were reported at the 2024 ASCO Annual Meeting, he states. At 1 year following transplantation, the overall survival (OS) rate within the reduced-intensity conditioning stratum in ACCESS was 79% (95% CI, 68%-87%). This outcome was comparable with the OS rate of 77% (95% CI, 71%-82%) observed with bone marrow grafts in the phase 3 BMT CTN 1703 study (NCT03959241).

Transplants using mismatched related donors have historically been challenging due to the higher incidence of GVHD, Al Malki notes. However, the rates of GVHD and other complications in the ACCESS study were comparable to those in HLA-matched donor recipients. In the reduced-intensity conditioning cohort, the rate of grade 2-4 acute GVHD was 43% (95% CI, 32%-55%), the rate of grade 3/4 GVHD was 9% (95% CI, 3%-16%), and the rate of moderate/severe chronic GVHD was 9% (95% CI, 3%-17%). In the BMT CTN 1703 PTCy arm, these rates were 56% (95% CI, 49%-62%), 8% (95% CI, 5%-12%) and 7% (not reported), respectively. Overall, these data highlight the efficacy and safety of using reduced-intensity conditioning PBSC transplantation from MMUD, which could significantly expand patient access to stem cell transplants, Al Malki concludes.