Jeffery Auletta, MD, is a blood and marrow transplant physician at Nationwide Children’s Hospital.

Monzr M. Al Malki, MD, is an associate professor in the Division of Leukemia and Hematopoietic Cell Transplantation, director of Unrelated Donor BMT Program, and director of Haploidentical Transplant Program at City of Hope.

Drs Al Malki on Outcomes With PTCy-Based GVHD Prophylaxis 

“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.

Videos

Monzr Al Malki, MD and Jeffery J. Auletta, MD discuss evaluating PTCy-based GVHD prophylaxis in hematologic malignancies.

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

Jeffery Auletta, MD, discusses the impact of post-transplant cyclophosphamide in hematologic malignancies.

Dr Auletta on the Impact of Post-Transplant Cyclophosphamide in Hematologic Malignancies

Jeffery Auletta, MD, physician, blood and marrow transplant (BMT), Hematology/Oncology/BMT, Infectious Diseases, Nationwide Children's Hospital; professor, pediatrics, The Ohio State University College of Medicine; member, the Leukemia Research Program, The Ohio State University Comprehensive Cancer Center; member, the Center for Regenerative Medicine and Cell-based Therapies, The Ohio State University, discusses the outcomes of comparing graft-versus-host disease (GVHD)–free, relapse-free survival (GRFS) and overall survival (OS) between 8/8 and 7/8 unrelated donor hematopoietic cell transplantation (HCT) with post-transplant cyclophosphamide (PTCy) in patients with acute leukemia or myelodysplastic syndromes (MDS).

PTCy has now become standard practice for preventing GVHD in both recipients of HLA-matched and -mismatched unrelated donor (URD) allografts, leading to successful HCT regardless of patient ancestry. The objective of this investigation was to discern disparities in OS and GRFS between 8/8 and 7/8 unrelated donor allografts when using PTCy compared with calcineurin-inhibitor (CNI)–based approaches, and to evaluate the impact of PTCy on remaining outcome differences due to HLA disparities.

Secondary objectives included comparing GRFS, OS, and other clinical outcomes among 8/8 and 7/8 URD recipients utilizing either PTCy- or CNI-based prophylaxis. The study involved adult patients undergoing initial URD HCT between January 2017 and June 2021.

The findings from this study demonstrate that using a mismatched URD yields similar outcomes to those observed when using a matched URD when employing PTCy as prophylaxis against GVHD, Auletta reports. Notably, although there was an outcome disparity in OS between 8/8 and 7/8 URD transplants with CNI-based GVHD prophylaxis, such a disparity was not observed when using PTCy, he explains.

Additionally, GRFS was comparable between 8/8 and 7/8 URD transplants with CNI-based GVHD prophylaxis but showed equivalence when using PTCy-based GVHD prophylaxis, with the latter demonstrating superior GRFS compared with URD transplants receiving CNI-based GVHD prophylaxis, Auletta concludes.

Jeffery Auletta, MD

Articles

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

Dr Auletta on the Impact of Post-Transplant Cyclophosphamide in Hematologic Malignancies