Comparing 1-Year OS and RFS in Patients Treated With ABA in Combination With a CNI/MTX vs ATG or PT-Cy Following Allogenic HCT

In this video, Leslie S. Kean, MD, PhD, discusses the abstract "A Real-World Evidence Comparison of 1-Year Overall Survival and Relapse-Free Survival Between Patients Treated With Abatacept in Combination With a Calcineurin Inhibitor and Methotrexate Versus Antithymocyte Globulin or Post-Transplant Cyclophosphamide Following Allogeneic Hematopoietic Cell Transplantation," presented at ASH 2022.

Transcript: 

I’m Leslie Kean, I’m at Boston Children's Hospital and Dana-Farber Cancer Institute, and I'm a professor at Harvard Medical School. So, we presented our abstract this year at ASH 2022, it's an abstract that describes real-world evidence that was submitted to the FDA as part of the approval submission for abatacept for acute GVHD prevention, and then an extension of that study to look at one year outcomes of abatacept plus CNI and methotrexate for acute GVHD prophylaxis versus a variety of other prophylaxis strategies.

What we were able to do by partnering with the Center for International Blood and Marrow Transplant Research, or the CIBMTR, specifically with two major collaborators there, Dr Linda Burns and Dr Marcelo Pasquini and their team, we were able to use the very detailed data that CIBMTR collects to do a real-world evidence analysis of the outcomes of abatacept plus CNI methotrexate versus a variety of prophylaxis regimens. So we compared the abatacept regimen to what we called CNI methotrexate, that has been the standard in the field for many years, we compared it to CNI methotrexate plus ATG, and then very importantly, we also compared it to PTCY, that's post-transplant cyclophosphamide, plus tacrolimus, plus MMF, and what we found was that the abatacept containing regimen in the real-world analysis, first of all met the endpoint that the FDA had stipulated which is day 180 overall survival benefit compared to CNI methotrexate, and it was absolutely clear that the ABA regimen was better compared to CNI methotrexate at that time point.

We then did an extended analysis both in match unrelated donor transplant patients and what we call seven out of eights, or mismatch and unrelated donor transplant patients, and we found that by extending out even to a year, that results stood and abatacept gave improved overall survival and relapse-free survival in both those patient groups, compared to CNI methotrexate.

What we then went on to do is compare it to another addition to CNI methotrexate, called antithymocyte globulin, or ATG. Our results were very clear as well that ABA containing regimens, so ABBA plus CNI methotrexate, gave improved one year overall survival and relapse survival very clearly better with very statistically significant outcomes for both the seven out of eight and the eight out of eight groups, and then finally, we compared abatacept to what we really believe may be the new standard in the field, there's a late breaking abstract at this ASH meeting that's going to describe a study using PTCY based prophylaxis, and what we found was that the ABA results were very similar to the PTCY results, there was a slight increase favoring ABA numerically for some of the outcomes, but statistically they were in a dead heat. This is a very important result because it suggests that in the future it would be very important to prospectively study abatacept versus PTCY containing regimens because remember, this was a real world evidence retrospective analysis, these results suggest that prospectively we should compare those two regimens head to head and I think maybe even more importantly, think about ways that we can combine abatacept with PTCY potentially to find the optimal acute GVHD prophylaxis strategy.

I will say that another really important outcome of the ABA study, both the ABA2 study that was published previously, the real-world evidence analysis that we used to submit to the FDA, is that it shows that we could safely and effectively transplant patients that do not have a full HLA match, those seven out of eight mismatch unrelated donor transplants. This is critical because patients of ethnic minority, ethnic and racial minorities, often cannot find a fully matched donor and so if we can make seven out of eight transplants safer, we increase the number of safe and effective transplants that we can deliver to all of our patients.

Source: Kean L, Burns L, Kou T, et al. A Real-World Evidence Comparison of 1-Year Overall Survival and Relapse-Free Survival between Patients Treated with Abatacept in Combination with a Calcineurin Inhibitor and Methotrexate Versus Antithymocyte Globulin or Post-Transplant Cyclophosphamide Following Allogeneic Hematopoietic Cell Transplantation. Presented at the ASH Annual Meeting & Exposition; December 10-13, 2022; New Orleans, LA, and virtual. Abstract 571.