New approach ‘redefining what is a suitable donor’ for stem cell transplant
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Key takeaways:
- Peripheral blood stem cells showed similar outcomes to mismatched bone marrow grafts.
- People of color made up half of enrolled patients.
CHICAGO — Interim results from a phase 2 study showed positive survival outcomes for individuals who underwent peripheral blood stem cell transplantation for hematologic malignancies.
This is despite the ACCESS study using grafts from mismatched unrelated donors, which have had historically poor treatment outcomes, according to study investigators.
Researchers also estimated that more than half of patients treated in the study will survive without relapse or developing graft-versus host disease (GVHD) one year after treatment with a regimen that included reduced-intensity conditioning and post-transplant cyclophosphamide (PTCy)-based GVHD prophylaxis.
Among the study cohort of adults, half included people of color, thus better representing the U.S. population and showing strong real-world implications of the findings, researchers said.
“The results contribute to the growing body of transplant practice-changing evidence driving those novel approaches to care for patients and save more lives,” Monzr M. Al Malki, MD, associate professor in the department of hematology and hematopoietic cell transplantation and director of the Unrelated Donor BMT Program at City of Hope, told Healio. “This study mainly provides evidence that by doing this type of transplant in this platform, we are able to have safe and effective access to those patients who don’t have matched donors, and we are hopeful that this will continue to be optimized to produce better results in the future.”
Background and methodology
Previous studies have shown inferior survival outcomes using HLA-mismatched unrelated donor bone marrow grafts and calcineurin-based GVHD prophylaxis in adults.
Researchers conducted the multicenter ACCESS study to assess the impact of PTCy-based GVHD prophylaxis on OS following HLA-mismatched unrelated donor transplantation with reduced-intensity conditioning in patients with advanced hematologic malignancies.
The prospective study included three cohorts: two for adults based on conditioning regimen intensity using peripheral blood stem cells (PBSCs) and one pediatric cohort using bone marrow grafts.
Researchers reported the results of a planned interim analysis of the first 70 adults (median age, 65 years; 50% men; 48% non-Hispanic white) enrolled in the reduced-intensity conditioning PBSC transplant cohort. Fifty-three percent of patients in the group had a diagnosis of acute myeloid leukemia.
OS at 1 year after transplantation served as the study’s primary endpoint.
Results
Researchers noted that donors had a median age of 25 years (range, 18-35; men, 44.3%; HLA match level 7/8 = 67%, 6/8 = 27%, 5/8 = 6%). Conditioning regimens included fludarabine/melphalan (63%), fludarabine/busulfan (20%) and other assorted regimens (17%).
Researchers observed an OS at 1 year after transplant of 79% (95% CI, 68-87).
Additional secondary endpoint results reported included GVHD-free relapse-free survival of 51% (95% CI, 39-62), primary graft failure by day 28 of 6% (95% CI, 2-14), nonrelapse mortality of 13% (95% CI, 6-22), and a relapse rate of 21% (95% CI, 13-32).
Safety results showed 43% experienced grade 2 to grade 4 acute GVHD (95% CI, 31-55), 9% grade 3 to grade 4 acute GVHD (95% CI, 3-16) and 9% NIH moderate or severe chronic GVHD (95% CI, 3-17).
Next steps
Researchers noted similar OS for this cohort compared with their prior study using bone marrow grafts.
“I don’t think it’s a coincidence,” Steven Devine, MD, chief medical officer of NMDP and senior scientific director at Center for International Blood and Marrow Transplant Research, told Healio. “When we looked at the data from our original study 15-MMUD and then designed the ACCESS study, we had hoped for an OS at 1 year of about 75% because we felt that that would be close enough to the results of the prior study.
“These are the older patients who can’t necessarily withstand the most stringent preparation for transplant,” he added. “But it still tells us that this post-transplant cyclophosphamide kind of levels the playing field and allows us to do these mismatched transplants and still expect outcomes quite similar to what we would see in matched recipients — that’s what we think is the game changer here. We’re redefining what is a ‘suitable donor’ and that really expands options for all patients in need of a transplant.”
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Al Malki MM, et al. Abstract 6503. Presented at: ASCO Annual Meeting; May 30 – June 4, 2024; Chicago.
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