Encouraging results using mismatched unrelated donors in stem cell transplantation

Dr Monzr Al Malki – City of Hope National Medical Center, Duarte, USA

Dr Steven Devine – Center for International Blood and Marrow Transplant Research, Minneapolis, USA and Chief Medical Officer of NMDP

MAM:    In this abstract we presented in ASCO we are showing early and exciting results of the first cohort of the ACCESS study which is a large-scale multicentre prospective clinical trial from more than 30 transplant centres over the country. In this cohort that we presented, older patients with blood cancer would receive a reduced intensity preparative regimen followed by peripheral blood stem cell graft from a mismatch related donor.

What was the methodology of the study and the results?

MAM:    In this novel approach, which included the use of an old chemotherapy called cyclophosphamide given shortly after transplant, we showed that this approach was safe, with less graft-versus-host disease and complications, and effective, with excellent one-year overall survival close to 80%. Those outcomes are usually comparable to what we see in a fully matched donor transplant using the same platform. In other words, this innovative approach can greatly expand patient access to a safe and effective stem cell transplant, regardless of HLA matching degree.

What will be the impact of the results?

MAM:    In this study it shows that collaboration between NMDP and transplant centres like City of Hope here is important to close the gap of finding a donor for every patient who is in need of transplant to survive. Here in City of Hope we are trying to advance the representation also of diverse populations in oncology clinical trials, not only to generate better and more accurate data but also to represent the diversity of the United States and also to include those who would benefit the most from such innovative therapies.

What is the future of this study?

SD:        First I’d like to explain how important the ACCESS study is to NMDP and its vision of creating a world where everyone has access to live-saving cell therapy. That’s really what the ACCESS trial is all about. It’s part of an ambitious strategic initiative that we embarked on so that everyone truly could have a donor for whatever disease that may benefit from transplant. So the ACCESS study was the second in a series of studies conducted under that Donor for All initiative. The first study we had demonstrated that patients who had mismatched unrelated donor bone marrow transplants could have very good outcomes. The ACCESS study was focused on looking at donor peripheral blood versus bone marrow because peripheral blood donation is easier for donors and it’s easier to supply because you don’t need an operating room to procure the cells.

Again, as Dr Al Malki, outlined, the outcomes were very promising in this first planned analysis of 70 older patients who had blood cancers in need of a transplant. None of these patients had fully matched donors which are traditionally the best way to assure a good outcome. But what was of really significant interest and impact is that despite the fact that the donors were less than fully matched with the recipients, the outcomes appeared to be similar to those we would observe after a fully matched transplant. So the impact of that is great and will truly increase access to transplantation for all patients, regardless of their ancestry.

In terms of the future, I mentioned that this was just the first 70 patients who were transplanted on the study. We actually transplanted more than 260 adult recipients and there’s another cohort that’s looking at paediatric recipients. So over the next year we will also be reporting outcomes in all 260 adult recipients. But the plans are to put together a manuscript first on these next 70. Then currently we have a third study called OPTIMIZE where we’re actually trying to make these transplants even safer by reducing the dose of the drug used to prevent graft-versus-host disease called cyclophosphamide. The hope is that we will reduce the number of infections that patients experience after a mismatched unrelated donor transplant in that trial. That’s an ongoing trial which we hope to complete over the next 18-24 months.

Is there anything else you would like to add?

SD:        Traditionally the best outcomes were with matched unrelated donors but even though patients have access to the NMDP registry and more than 41 million potential donors worldwide, less than 50% of racially or ethnically diverse patients can find a full match which is why we need to redefine what is considered a suitable donor through this series of studies.