Age Alone Is No Barrier to Allo-HCT for AML, Data Indicate

Older age alone should no longer be considered a disqualifying factor for offering allogeneic hematopoietic cell transplantation (allo-HCT) to patients with acute myeloid leukemia (AML), according to results of a large study that followed posttransplant outcomes over 2 decades.

Acute myeloid leukemia is a disease of older patients. | Image Credit: © Dzmitry - stock.adobe.com

Between 2000 and 2021, both 3-year cumulative relapse incidence (RI) and nonrelapse mortality (NRM) significantly decreased for the 7215 patients, all aged between 65 and 80 years. The 3-year leukemia-free survival (LFS) and overall survival (OS) significantly improved as well.

This was among the largest real-world analyses to date to assess trends over time and predictive factors for patients with AML in this age range who received allo-HCT. It was published in Clinical Cancer Research.

The patients’ median age was 68 years, and median follow-up was 40 months. Patient data were from the European Society for Blood and Marrow Transplantation, a working group of more than 600 transplant centers that report results to a central registry.

The investigators divided their time frame into 3 sectors: 2000-2009 (728 patients), 2010-2014 (1775 patients), and 2015-2021 (4712 patients).

The 3-year cumulative RI decreased from 37% to 31%, then to 30% (P = .001) over the 3 time periods. NRM decreased from 31% to 31% to 27% (P = .003).

The 3-year LFS and OS improved from 32% to 38%, and then to 44% (P = .001) and from 37% to 42%, and then to 49% (P = .001), respectively, the authors reported.

In multivariate analysis, they pointed out, significant improvements in the RI, LFS, and OS were noted after 2015, regardless of disease status at transplant. Overall, 64% of patients received transplants after first complete remission (CR1), 14% at second or subsequent remission, and 22% while having active disease.

However, again in multivariate analysis, NRM was not significantly affected, which was “surprising particularly given all the advances in transplants over the past 2 decades,” the authors stated. They posited that one possible explanation is the older age of patients who received transplants in the 2015-2021 period.

Another possible explanation is the increased use of haploidentical transplants, rising from 0.7% in 2000-2009 to 18.6% in 2015-2021. This increase likely reflects improved outcomes after haplo-HCT with the use of posttransplant cyclophosphamide, they stated.

In contrast with NRM, “decreased RI may reflect a better selection of transplant candidates of older age,” they noted. Another likely factor has been improved induction regimens, which have incorporated novel agents like venetoclax.

Decreased RI may also be attributable to the significant improvement over time in patients with CR1, to personalized conditioning regimens, and to the increased use of prophylactic posttransplant pharmacologic interventions—particularly hypomethylating agents and FLT3 inhibitors, the authors explained.

In studying the frequency of graft-vs-host-disease (GvHD), they found that the incidence of chronic GvHD decreased from 35% (2000-2014) to 31% (2015-2021). GVHD-free survival and relapse-free survival rose from 22% to 34% over time.

Study limitations included a lack of information about minimal residual disease for most patients, especially those treated before 2015, as well as no data about the specific maintenance therapies patients received after allo-HCT.

“Despite the increasing use of targeted therapies, allo-HCT remains an important and potentially curative modality for patients with AML,” the authors said.

Their hope was that their study’s large-scale, real-world data would be able to serve as a benchmark for future investigations in this setting. In the meantime, they declared, the data clearly indicate “that the opportunity for transplant for the elderly should be mandatory and no longer an option.”

Reference

Bazarbachi A, Labopin M, Moukalled N, et al. Improvements in posttransplant outcomes over two decades in older patients with acute myeloid leukemia in the EBMT ALWP Study. Clin Cancer Res. Published online March 22, 2024. doi:10.1158/1078-0432.CCR-23-3673