June 2024

Presented at the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting, preliminary results from the ACCESS clinical trial suggest promising outcomes for peripheral blood stem cell (PBSC) mismatched unrelated donor (MMUD) sources using reduced intensity conditioning (RIC). ACCESS is a prospective multi-center clinical study designed to evaluate the effectiveness of post-transplant cyclophosphamide (PTCy) based graft-versus-host disease (GVHD) prevention on overall survival in MMUD allogeneic hematopoietic cell transplant (alloHCT). Encouraging 1-year survival rates, similar to what was demonstrated previously with bone marrow, reinforce the potential of MMUD to expand access to HCT by ensuring a donor for all, especially for racially and ethnically diverse patients.

Download a PDF of the study highlights and citation here.

Background

Optimal donors for alloHCT have traditionally been HLA-matched siblings, available to about 30% of patients. For those without a matched sibling, an 8/8 HLA-matched unrelated donor (MUD) is often the next best option. However, MUD availability varies by ancestry, ranging from 29% for Black patients to 79% for White non-Hispanic patients. Using an MMUD matched at ≥4/8 HLA markers could potentially provide access to nearly all patients needing HCT. Previous research, such as the 15-MMUD trial, showed promising overall survival (OS) rates using bone marrow and PTCy-based GVHD prevention. The ACCESS trial (NCT04904588) aims to determine if similar OS results can be achieved using PBSC (the most common stem cell source) with PTCy.

Methods

The study includes 3 cohorts: 2 for adults based on conditioning intensity (myeloablative or RIC) and 1 pediatric cohort using myeloablative conditioning. Adult patients were stratified into myeloablative conditioning and RIC based on physician clinical judgement, all receiving PBSC. The pediatric cohort receives myeloablative conditioning using bone marrow. Accrual to the adult cohorts of the trial is complete, with over 260 patients in follow-up, while pediatric accrual continues. The first 70 adult patients enrolled in the RIC cohort were analyzed.

Results

Patients were treated at 13 transplant centers with a median age of 65 years (50% male). Ethnic diversity was high, with 52% of patients classified as racially or ethnically diverse. Patients received transplants for acute myeloid leukemia (AML, 53%), myelodysplastic syndromes (MDS, 26%), acute lymphoid leukemia (ALL, 7%), and other blood cancers (14%). The median donor age was 25 years (56% female). HLA match levels were 7/8 (67%), 6/8 (27%), and 5/8 (6%). RIC regimens primarily included fludarabine and melphalan (63%).

1-year post-HCT, the OS rate was high at 79%. Other clinical endpoints are included in the Figure below.

Key Takeaways

The preliminary results from the ACCESS trial show encouraging 1-year OS rates in patients receiving RIC MMUD PBSC alloHCT with PTCy. Notably, half of the enrolled patients were people of color, highlighting the trial's diversity and importance of MMUD for diverse patient populations. The OS rates observed were similar to a previous trial using bone marrow in adults. Rates of GVHD and other complications were comparable to those seen in HLA-matched donor recipients receiving PTCy, suggesting that MMUD HCT could significantly expand access to life-saving therapies for patients with advanced blood cancers. The study's findings underscore the potential for safe and effective use of MMUD HCT, helping to ensure a donor for all patients in need of alloHCT, including diverse patient populations.

Figure

This figure displays the clinical endpoints at 1-year for the preliminary results of the ACCESS trial.