In older patients with acute myeloid leukemia (AML) in first complete remission (CR1), outcomes after allogeneic hematopoietic stem cell transplantation (HCT) appear related to features present during diagnosis. This is according to the results of a study recently presented in the journal Blood.
Patients with AML who are older tend to have worse relapse and survival outcomes after HCT than younger patients do, the study investigators explained in their report. Treatment approaches differ by age, so the investigators had an aim of determining factors that may influence outcomes for older patients with AML with HCT.
In this multicenter study, the researchers examined samples obtained from patients with AML who were age 60 years or older at diagnosis and who underwent HCT during first complete remission, with or without hematologic recovery. Reduced-intensity conditioning had been given to 91% of patients. The researchers performed targeted mutational analyses of bone marrow or peripheral blood samples from all patients, with samples collected prior to induction chemotherapy.
Targeted duplex sequencing was performed in a subset of patients with samples collected during CR1, prior to HCT. In this subset analyzed during CR1, patients were categorized as being minimal residual disease (MRD) positive or negative, depending on the presence and nature of any persistent mutations.
The full study cohort included 295 patients, and the subset analyzed during CR1 included 192 patients. Among survivors, the median follow-up was 44 months (range, 6.7-155.3). Sequencing of preinduction samples suggested a high prevalence of high-risk genetic features in this population.
Persistent baseline mutations were found in 79.7% of patients analyzed at CR1. In the subset of 192 patients evaluated during CR1, 39 patients cleared all mutations by remission, 35 patients showed persistent DNMT3A or TET2 mutations only, and 118 patients showed other persistent mutations. Patients who cleared all mutations were considered MRD negative, while those with only DNMT3A or TET2 persistent mutations were grouped with MRD-negative patients for analyses, based on the expected nature of mutations in either of these 2 genes. Patients with other persistent mutations were considered MRD positive.
The researchers performed a multivariable analysis for leukemia-free survival (LFS) using baseline genetic and clinical features, and patients were placed into 4 risk categories using this model. The 3-year LFS rates by category were 86% for the low-risk group, 54% for the intermediate-risk group, 35% for the high-risk group, and 9% for the very high-risk group.
A univariable analysis suggested that MRD-positivity in remission was associated with inferior LFS, compared with patients who were MRD negative or possessed only DNMT3A or TET2 persistent mutations. However, an analysis adjusted for baseline risk factors indicated MRD positivity was not an independent factor for LFS.
The researchers concluded that baseline risk factors were important drivers of LFS outcomes. “Taken together, our results provide a framework for developing risk-adapted strategies and interpreting the relative prognostic impact of baseline and remission genetics in older patients with AML who are transplant candidates,” the researchers wrote in their report.
Disclosures: Some authors have declared affiliations with or received grant support from the pharmaceutical industry. Please refer to the original study for a full list of disclosures.
Murdock HM, Kim HT, Denlinger N, et al. Impact of diagnostic genetics on remission MRD and transplantation outcomes in older patients with AML. Blood. 2022;139(24):3546-3557. doi:10.1182/blood.2021014520