Allogeneic Hematopoietic Cell Transplantation (HCT) for Adults with Acute Myeloid Leukemia Older Than Age 60

Background: Advances in transplant platforms and supportive care have enabled allografting in adults with acute myeloid leukemia (AML) older than age 60 (up to their late seventies) but conflicting data exist on their relative outcomes.

Methods: We retrospectively studied all 493 adults aged ≥60 years with AML or myelodysplastic neoplasm (MDS)/AML who underwent a first allogeneic HCT between 2006 and 2023 at our institution. The analysis aimed to assess the post-HCT outcomes with a specific focus on categorizing the patients by age groups (60-64, 65-69, and ≥70 years).

Results: Among 493 patients, 184 (37%) were aged 60-64, 189 (38%) 65-69, and 120 (24%) ≥70 years. There were no significant differences in gender, disease type, cytogenetic risk, remission status, positivity for measurable residual disease (MRD) by multiparameter flow cytometry, cytogenetic abnormalities, blood count recovery, stem cell source, or HCT-CI among the age groups. However, younger patients more frequently received myeloablative conditioning (MAC) (P<0.001).

Regression models were used to assess the relationship between age and post-HCT outcomes. After multivariable adjustment, patients aged ≥70 years had a statistically significantly higher risk of non-relapse mortality (NRM) than those age ≥60-64 (hazard ratio [HR]=1.75 [95% confidence interval: 1.10-2.79]; P=0.019), and their risk of death was statistically non-significantly higher (HR=1.32 [0.96-1.82]; P=0.085), whereas risks of relapse and relapse/death were similar. There were no statistically significant differences regarding relapse, relapse-free survival (RFS), overall survival (OS), or NRM between patients aged 60-64 years and those aged 65-69 years after adjustment. Across all age cohorts, there was a statistically significant association between HCT-CI score ≥4 and increased NRM (HR=2.12 [1.36-3.31]; P<0.001), RFS (HR=1.39 [1.05-1.84]; P=0.023), and OS (HR=1.52 [1.14-2.04]; P=0.005) but not relapse (P=0.67) after adjustment. Findings in the subset patients with AML (n=416) and those who received an allograft from a 10/10 HLA-matched related or unrelated donor (n=369) were similar to the entire study group. Among patients receiving nonmyeloablative (NMA) conditioning (n=240), there was no significant association between age group and relapse, RFS, OS, or NRM. In contrast, among patients allografted after reduced-intensity conditioning (RIC; n=144), age ≥70 years was associated with higher risk of relapse (HR=4.19 [1.31-8.10]; P=0.011, shorter RFS (HR=3.42 [1.88-6.23]; P<0.001) and OS (HR=3.16 [1.66-5.99]; P<0.001), and higher risk of NRM (HR=4.19 [1.88-9.36]; P=0.001). Patients aged 60-64 and 65-69 but not those aged ≥70 had a significantly lower risk of relapse when receiving RIC compared to those receiving NMA. The risk of NRM was similar for those getting NMA conditioning or RIC in the 60-64 age group. Patients ≥70 years had substantially higher NRM with RIC compared to NMA conditioning (HR=3.43 [1.68-7.00]; P<0.001). This resulted in a statistically significantly better RFS (HR=0.55 [0.33-0.94]; P=0.027) with RIC among patients aged 60-64, whereas RIC was associated with worse RFS (HR=2.03 [1.22-3.37]; P=0.006) and OS (HR=2.01 [1.17-3.47]; P=0.012) in patients aged ≥70 relative to those receiving NMA conditioning.

Conclusion: For patients 60-64 years, reduced relapse risk and no increase in NRM led to improved RFS and OS with RIC compared to NMA conditioning. Uncertainty regarding optimal conditioning intensity remains for patients aged 65-69, where RIC showed reduced relapse risk but increased NRM, resulting in comparable RFS and OS to NMA conditioning. However, in patients aged ≥70, RIC was associated with higher NRM and worse RFS and OS compared to NMA conditioning but similar relapse risk. Since Patients aged ≥70 faced more toxicities with RIC and did not benefit from reduced relapse risks, our data suggest such older individuals should receive HCT after NMA conditioning.

Sandmaier:Actinium Pharmaceuticals: Other: Attended Advisory Board Meeting; Royalty agreement with employer (Fred Hutch. Othus:BMS: Other: Data Safety Monitoring Board; Grifols: Other: Data Safety Monitoring Board; Merck: Consultancy; Glycomimetics: Other: Data Safety Monitoring Board; Biosight: Consultancy. Walter:Aptevo: Research Funding; Celgene/Bristol Myers Squibb: Research Funding; ImmunoGen: Research Funding; Janssen: Research Funding; Jazz: Research Funding; Kite: Research Funding; Kura: Research Funding; Pfizer: Research Funding; VOR: Research Funding; Wugen, Inc.: Consultancy.