Muhammad Bilal Abid, MD, CIBMTR® (Center for International Blood and Marrow Transplant Research), Department of Medicine, Medical College of Wisconsin, Milwaukee, discusses findings from a study that compared outcomes of patients with acute myeloid leukemia (AML) who underwent allogeneic hematopoietic stem cell transplant (alloHSCT) with younger matched unrelated donors vs older matched sibling donors.

The study found that incidence of relapse was reduced in patients with AML who underwent alloHSCT with younger matched unrelated donors vs older matched sibling donors, and highlighted that a younger matched unrelated donor-type exerts a stronger graft-versus-leukemia effect, and should be preferred when available, particularly in patients with AML at higher risk for post-alloHSCT relapse.

Transcript:

My name is Muhammad Bilal Abid. I'm an assistant professor of medical oncology, hematology and infectious diseases at the Medical College of Wisconsin in Milwaukee, Wisconsin. I'm here at the American Society of Hematology meeting to present our results of a large CIBMTR® study that was intended to compare differences between younger matched unrelated donor and older matched sibling donor, particularly in older patients with acute myeloid leukemia who undergo allogeneic transplantation. The premise of this study primarily included that we see that there is a tremendous rise in the incidence of AML. The median age of onset of AML is now in excess of 68 years. We have to find better ways to get geriatric population better access to transplant, as well as keep working on improving outcomes of those who undergo transplants.

Now, in large analyses that have been conducted in the past, we have seen that they either showed that a matched sibling donor (MSD) was equal to a matched unrelated donor (MUD) and donor age doesn’t generally matter. Some of the very recent evolving data in other disease settings really show that a younger donor may create an impact in terms of improving survival outcomes and relapse reduction. With that in mind, we hypothesize that older patients with AML who undergo transplantation with younger donors would have superior outcomes as compared to those who undergo transplantation with older matched sibling donors, primarily because senescence has its own issues, and aging has its own immunological issues. Also, they can carry higher comorbidities. With that in mind, our primary aim was to compare relapse rate. Secondarily we wanted to see overall survival, disease free survival, non-relapse mortality, and primary causes of death in a descriptive manner between the 2 donor arms.

In the main results of the study, there were no differences in UD variable analysis on each one of these four outcomes, however, multi-variable analysis clearly showed that younger matched unrelated donors conferred a significant reduction in relapse rate as compared to older matched sibling donors. We had to look at non-relapse mortality (NRM) alongside [this], and we could only do that in 2 cohorts—earlier years, 2011 through 2015, and then 2016 through 2018, because there were significant interaction between the main effect, which is the donor type, and transplant year.

While younger MUDs were associated with higher NRM, in the earlier years, they were associated with lower NRM in the more recent years, as compared to older matched sibling donors. Turns out that the absolute relapse reduction associated with younger matched unrelated donors did not translate into leukemia-free survival or overall survival benefit, although the P-value was nearly statistically significant in terms of multi-variable analysis in DFS only.

The 5-year adjusted cumulative incidence of relapse was also significantly lower with younger MUDs as compared to older MSDs. And then again, corresponding to the remaining multi-variable analysis results, the NRM was higher with younger MUDs as compared to older MSDs in the earlier years. But there was no real significant difference in the recent years, really depicting that we have learned how to do transplant better over the last decade in terms of supportive care, GVHD prophylaxis, infection prevention, et cetera.

More importantly, while there was no difference in OS, the cumulative incidents and OS probability at 5 years, there was a significant PFS reduction at 5 years with younger MUDs as compared to older MSDs match sibling donors. With these results, our group, we conclude that— the curves really divorce each other; the relapse curves divorce each other at the 6-month mark—which clearly tells us that it's likely to be a GVL effect driven by the donor, rather than conditioning driven impact. Similar to the case with disease-free survival (DFS), we conclude that younger matched unrelated donors should be preferred over older matched sibling donors whenever both are available, primarily because younger matched unrelated donors exert a much stronger GVL effect compared to older matched sibling donors. Thank you.

Source:

Abid MB, Estrada-Merly N, Zhang M, et al. Comparison of Allogeneic Hematopoietic Cell Transplantation Outcomes from Younger Matched Unrelated Donor Versus Older Sibling Donor for Acute Myeloid Leukemia. Presented at the ASH Annual Meeting & Exposition; December 10-13, 2022; New Orleans, LA, and virtual. Abstract 374.