A recent study, the NMDP-sponsored ACCESS study (NCT04904588), aims to revolutionize access to stem cell transplants for patients with partially matched or mismatched donors, particularly focusing on improving outcomes for ethnically diverse individuals. The disparities in finding an 8/8 HLA-matched donor among different racial and ethnic groups are striking, with Black and African American patients having a 29% chance, Hispanic patients a 48% chance, and non-Hispanic White patients a 79% chance of finding a suitable donor. This study is part of the broader Donor for All initiative by the NMDP, striving to establish effective transplant approaches for patients using mismatched unrelated donors with outcomes similar to traditional matches.
The rationale behind the ACCESS study, as explained by Dr. Antonio Jimenez Jimenez, is two-fold: to enhance the outcomes of partially matched or mismatched transplants and to address the limited transplant options for ethnically diverse patients. Building on the findings of the 15-MMUD study, ACCESS offers a more streamlined approach using peripheral blood stem cells, involving a larger number of centers and a more diverse patient population, including a pediatric cohort. The study’s design as a phase 2, multicenter, nonrandomized trial focused on adult patients receiving their first allo transplant from mismatched unrelated donors, ranging from 4/8 to 7/8 mismatches.
Key outcomes from the ACCESS study indicate promising results comparable to fully matched donors, with one-year survival rates exceeding 80% for both myeloablative and reduced-intensity conditioning groups. The incidence of severe GVHD was notably low, showcasing the feasibility and safety of utilizing mismatched donors. Additionally, the study found no significant survival differences between single antigen mismatches (7/8) and lower mismatches, suggesting the potential to identify suitable donors for patients regardless of racial or ethnic backgrounds, thereby expanding access while optimizing donor selection based on non-HLA factors.
Moving forward, the research team aims to further improve outcomes by reducing toxicity through studies like OPTIMIZE (NCT06001385), exploring lower doses of cyclophosphamide to maintain efficacy while minimizing adverse effects. By addressing biological barriers and demonstrating the safety and efficacy of these transplants, the ACCESS study contributes to breaking down other barriers to transplantation for ethnically diverse patients, such as referral biases and historical donor search strategies. Embracing a more holistic approach to donor selection could enhance patient outcomes by ensuring timely access to suitable transplants.
In conclusion, the ACCESS study represents a significant advancement in improving stem cell transplant access for diverse patient populations, highlighting the potential of mismatched unrelated donors to provide comparable outcomes to traditional matches. By expanding access and optimizing donor selection based on non-HLA factors, this research paves the way for more inclusive and effective transplant strategies, ultimately benefiting patients who may have limited donor options based on their racial or ethnic backgrounds.
Read more on targetedonc.com