ASH 2025 | The ACCESS study: impact of HLA disparity on transplant outcomes in patients receiving MMUD grafts

We share some of the results of the ACCESS trial. Specifically today, we reported the outcomes of patients receiving highly mismatched grafts, that is, transplants from a donor matched at a less than seven out of eight level, and we compare that to patients receiving a single antigen mismatched graft, seven out of eight. The preliminary results of the ACCESS trial were presented last year, and the focus of the study today was to evaluate the impact of levels of mismatch in transplant outcomes. 

And what we found was that outcomes were similar between patients receiving a single antigen mismatch and a highly mismatched graft. And this has very important implications for access and equity. Patients who are ethnically and racially diverse are not only underrepresented in the registry, but they also have a much lower likelihood of identifying a fully matched donor. So oftentimes for these patients, the only option to proceed with transplant is to receive a highly mismatched graft. The problem is that when we use traditional GvHD prophylaxis, with each degree of mismatch, we pay a penalty and there is an increase in mortality when traditional prophylaxis is used. So the idea was, the question that we wanted to understand was, if with the PTCy platform, outcomes between highly mismatched graft recipients were comparable to that of patients receiving a single antigen mismatch. And what we found was that survival and other important secondary endpoints were comparable. 

We also looked at registry data from today showing that availability of donors, irrespective of race and ethnicity, increases significantly when we are permissive to high degrees of mismatch. And that means that this graft source has the potential to improve access and equity, particularly for patients who are ethnically diverse, but also by counting on a much larger donor pool, we can optimize non-HLA donor factors that are known to affect transplant outcomes. So we can find a donor for every patient, but we can also find a better donor for that individual patient that you’re seeing at the time. We have additional studies building on this platform. We’re trying to evaluate the combination of cyclophosphamide, changing or reducing the dose of cyclophosphamide to minimize some of the toxicity and see if we can continue to provide safe transplantation with good protection against rejection and GVHD while also minimizing toxicity.

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