Survival Similar With MMUD Grafts in GVHD Care Regardless of Match Level

Patients who received a mismatch unrelated donor (MMUD) peripheral blood stem cell (PBSC) transplantation with a human leukocyte antigen (HLA)–locus level of less than 7 for graft-versus-host disease (GVHD) prophylaxis experienced comparable outcomes to patients with an HLA-locus level of 7, according to findings from the phase 2 ACCESS trial (NCT04904588) presented in a press briefing at the 2025 American Society of Hematology (ASH) Annual Meeting and Exposition.¹

Findings from the trial revealed that the primary end point, 1-year overall survival (OS), was similar between the HLA match <7/8 group (n = 85) and the HLA match 7/8 group (n = 183). In the former, the 1-year OS rate was 85.6% (95% CI, 76.0%-91.5%) and in the latter, the rate was 78.6% (95% CI, 71.9%-83.9%).

Additionally, the estimated 1-year GVHD-free, relapse-free survival (GRFS) rate in the HLA match 7/8 group and the HLA match <7/8 group, respectively, was 51.1% (95% CI, 43.5%-58.2%) and 53.0% (95% CI, 41.2%-63.6%). Furthermore, the acute GVHD 6-month rates for grades II to IV and III to IV were 38.8% (95% CI, 31.7%-45.8%) and 8.2% (95% CI, 4.8%-12.8%) in the 7/8 match group vs 34.3% (95% CI, 24.3%-44.4%) and 7.1% (95% CI, 2.9%-14.0%) in the <7/8 match group. The estimated 1-year moderate-to-severe chronic GVHD rate was 11.3% (95% CI, 7.1%-16.4%) vs 7.7% (95% CI, 3.1% 15.1%) in each respective arm.

Moreover, the primary graft failure rate by day 28 was 3.1% (95% CI, 0.8%-7.6%) in the 7/8 match group and 6.5% (95% CI, 1.8%-15.7%) in the <7/8 match group. The respective estimated 1-year non-relapse mortality (NRM) and relapse rates were 13.7% (95% CI, 9.2%-19.1%) and 17.1% (95% CI, 12.0%-22.9%) in the former group vs 8.4% (95% CI, 3.7%-15.6%) and 22.8% (95% CI, 14.1%-32.8%) in the latter group.

“Among adult recipients of less than 7/8 MMUDs, PBSC transplantation with post-transplantation cyclophosphamide [PTCy]–based [GVHD prophylaxis] enrolled on the ACCESS trial, survival at 1 year exceeded 80% and was comparable to that of 7/8 recipients,” Antonio M. Jimenez Jimenez, MD, lead of the Sylvester’s Mismatched Allogenic Transplant Program of the Division of Transplantation and Cell Therapy in the Miller School of Medicine at the University of Miami, stated in the oral presentation on the trial findings.¹ “Secondary end points such as relapse, NRM, and GVHD were also similarly favorable and consistent with outcomes reported in single-antigen mismatch recipients.”

The phase 2 trial enrolled patients 18 years and older with hematologic malignancies requiring hematopoietic stem cell transplantation (HCT), with an HCT-specific comorbidity index score of 0 to 4, PBSC donor product, a Karnofsky performance score of 60% or greater, and an available MMUD 35 years or younger with a 4 to 7 of 8 HLA match. Patients were stratified by receipt of myeloablative conditioning or a non-myeloablative/reduced-intensity conditioning regimen.

Patients in the phase 2 trial underwent conditioning and subsequently received a PBSC transplantation from a MMUD on day 0 of study treatment. On days 3 and 4 of treatment, patients underwent PTCy at 50 mg/kg per day, with mycophenolate mofetil (MMF) and tacrolimus (Prograf) given days 5 to 35 and 5 to 90 or 100 of study treatment, respectively. Post-transplant follow-up occurred on days 7, 14, 28, 56, 100, 180, and 365 of study treatment.

In the 7/8 and <7/8 groups, the median age was 63.3 years (range, 20.4-78.9) and 57.4 years (range, 24.3-77.9). A total of 51.9% vs 49.4% of each group were male, and 46.4% vs 64.7% were considered ethnically diverse. Most patients received a reduced-intensity conditioning regimen (71.6% vs 72.9%).

The most prevalent primary diagnosis was acute myeloid leukemia (AML), accounting for 44.8% of the 7/8 group vs 55.3% of the <7/8 group, followed by acute lymphocytic leukemia (ALL) and myelodysplastic syndromes (MDS), accounting for 21.9% vs 10.6% and 21.3% vs 15.3% of patients, respectively. Most patients had a Karnofsky performance score of 80 to 100 (92.3% vs 88.2%), an HCT-comorbidity index score of 0 to 2 (67.8% vs 62.4%), and for the <7/8 group, an HLA match level of 6/8 (82.4%).

Secondary end points in the phase 2 study included 1-year event-free survival, GRFS, progression-free survival, and overall toxicity.²

According to Jimenez Jimenez, among 2477 patients with no potential 8/8 MMUD matches examined between August 2020 and November 2025, all patients had multiple donor options at the <7/8 level, including for ethnically diverse patients, who encompassed 62.2% of the study population.

Disclosures: Jimenez Jimenez reported research funding from Abbvie and honoraria from the Saudi Society of Transplant Cell Therapy.

References

1. Al Malki MM, Bo-Subait S, Logan B, et al. Mismatching of unrelated donors beyond a single HLA-locus does not adversely impact outcomes at one year following transplantation: results from the NMDP sponsored ACCESS study. Blood. 2025;146(suppl 1):936. doi:10.1182/blood-2025-936
2. HLA-mismatched unrelated donor hematopoietic cell transplantation with post-transplantation cyclophosphamide (ACCESS). ClinicalTrials.gov. Updated July 29, 2025. Accessed December 6, 2025. https://tinyurl.com/yfkedf3j