Drs Al Malki and Auletta on PTCy GVHD Prophylaxis in Patients With HLA-UUMD

“The primary end point was overall survival at 1 year. This study met its primary end point and show promising results in that regard.”

Monzr Al Malki, MD, associate professor, Division of Leukemia and Hematopoietic Cell Transplantation, director, Unrelated Donor BMT Program, director, Haploidentical Transplant Program, City of Hope; and Jeffery J. Auletta, MD, chief scientific director, Center for International Blood and Marrow Transplant Research, senior vice president, Health Equity, National Marrow Donor Program, discuss findings from the phase 2 ACCESS trial (NCT04904588) evaluating post-transplant cyclophosphamide (PTCy)–based graft-vs-host disease (GVHD) prophylaxis following HLA-mismatched unrelated donor (MMUD) peripheral blood stem cell transplantation using myeloablative conditioning in patients with hematologic malignancies.

The study assessed 1-year overall survival (OS) as its primary end point, which was met, according to Al Malki. Patients who underwent a MMUD transplant with PTCy prophylaxis experienced a 1-year OS rate of 84%. In previously reported data from the phase 2 15-UUMD trial (NCT02793544), which also explored PTCy prophylaxis in the same patient population, the 1-year OS rate was 72%. The 1-year GVHD-free, relapse-free survival rate was 48% in for patients treated in ACCESS vs 38% for those treated in 15-UUMD. Notably, OS and GVHD outcomes were similar in ACCESS irrespective of whether patients had 1 HLA mismatch or at least 2 mismatches.

Auletta explains that these are intriguing results using the most common source for transplant—peripheral blood stem cells—in the content of patients with UUMD donors. These outcomes lay the groundwork for giving myeloablative conditioning to a larger number of patients, he says. By leveraging myeloablative conditioning in combination with MMUD transplantation, high-dose chemotherapy can also provide a graft-vs-leukemia effect to enhance disease control, Auletta says. By inducing donor-derived immunity and giving myeloablative conditioning, the PTCy-based strategy simultaneously eradicates malignant clones through both chemotherapeutic and immune-mediated mechanisms, he concludes.