Genomic Landscapes and Outcomes in Elderly Patients With AML

Although the median age of patients receiving a diagnosis of acute myeloid leukemia (AML) is 70 years, cohorts of younger patients with AML have been studied more extensively at the molecular level.

A poster presented at the European Hematology Association 2021 Virtual Congress found that the mutational landscape of elderly patients with AML is significantly different from that of younger patients.¹

Researchers from Germany utilized the AMLSG BiO Registry to evaluate 294 patients with AML who had a median age of 76 (range, 70-90) years. They identified 1095 mutations in 83 genes in the majority (97.2%) of patients. There was a median of 4 mutations per patient, with the majority (67.9%) being missense mutations followed by indels (19.5%), nonsense (10.2%), and splice site (2.4%) mutations.

The more frequently mutated genes were TET2, TP53, FLT3, SRSF2, DNMT3A, RUNX1, NRAS, NPM1, IDH2, ASXL1, SF3B1, and U2AF1. The majority (60.4%) of patients were classified as adverse risk based on the 2017 European LeukemiaNet (ELN) risk classification, while 27.3% had intermediate risk and 12.2% had favorable risk.

The authors noted that risk groups correlated with function classes:

• 68% of favorable, 67% of intermediate, and 49% of adverse risk groups had a methylation mutation
• 74% of favorable, 57% of intermediate, and 68% of adverse risk groups had a signaling mutation

There was no difference among the ELN risk groups regarding median overall survival (OS), which was 0.5 years. However, the median OS differed depending on treatment:

1. 0.97 years for patients treated with intensive chemotherapy
2. 0.76 years for patients treated with hypomethylating agents (HMAs)
3. 0.15 years for patients treated with best supportive therapy

“The mutational landscapes of elderly AML differs significantly from that of younger AML,” the authors concluded. “Adapting genomic classification of younger AML, distinct subgroups of prognostic relevance were also observed in elderly AML.”

A different poster from researchers in Italy found that BCL-2 positivity in elderly patients with AML was associated with a more favorable response to HMAs compared with conventional chemotherapy.²

They retrospectively analyzed 114 patients older than 65 years who were treated with induction chemotherapy (n = 51) or HMAs (decitabine or azacytidine; n = 62) in order to understand the prognostic role of BCL-2 expression in elderly patients with AML.

The majority of patients had BCL-2 expression (81 patients; 71%). In patients who were BCL-2 positive, the complete response (CR) was higher on HMAs (45.5%) compared with induction chemotherapy (23.5%; P = .04). For the overall population, the 1-year OS was superior with HMAs (51%) vs induction chemotherapy (26%; P = .07). Patients who were BCL-2 positive also had a better 1-year OS on HMAs (56%) vs induction chemotherapy (25%; P = .02).

References

1. Rücker FG, Hoyos M, Dolnik A, et al. Genomic landscape in patients with acute myeloid leukemia older than 70 years. Presented at: EHA2021 Virtual; June 9-17, 2021. Poster EP423.

2. Tiribelli M, Michelutti A, Cavallin M, et al. BCL-2 expression in elderly acute myeloid leukemia patients and impact on outcomes according to different therapeutic strategies. Presented at: EHA2021 Virtual; June 9-17, 2021. Poster EP477.