ASH 2018 | Genetic characterization of older acute myeloid leukemia patients treated in the phase III NILG 02/06 trial

On Sunday, 2^nd December 2018, at the  60^th American Society of Hematology Annual Meeting and Exposition, there was an oral session focused on measurable residual disease and genetic characterization of acute myeloid leukemia (AML). At this session, Chiara Caprioli from ASST Papa Giovanni XXIII, Bergamo, Italy, presented data from a study which examined the clinical outcomes of patients with AML aged ≥ 60 years, who were enrolled in the randomized phase III Northern Italy Leukemia Group (NILG) 02/06 study (NCT00495287) and were deeply genetically characterized. The main objectives of the study were to assess complete remission, overall survival rates and to investigate the patterns of response according to the European LeukemiaNet 2017 risk and the presence of lesions associated with secondary AML (sAML).

In the phase III NLG 02/06 study, 574 patients with newly diagnosed AML were enrolled between 2017 and 2012. Of these, 164 patients (median age = 63 years; range: 60–73) were aged ≥ 60 years and were randomized to receive conventional induction chemotherapy with idarubicin, cytarabine and etoposide (ICE; n = 82) or sequential high-dose cytarabine and idarubicin (sHD; n = 82), followed by consolidation courses with high dose cytarabine. At diagnosis, genetic characterization was obtained by either conventional cytogenetics (n = 145) or RT-PCR (n = 164). Next-generation sequencing (NGS) was performed for 51 patients with normal karyotype. Patients were re-classified as per the 2017 European Leukemia Net (ELN) guidelines. A myelodysplastic/myeloproliferative (MDS/MPN) related genetic signature was used for outcome correlation.

Key findings:

• A genetic MDS/MPN signature was observed in 42% (63/149) of patients
• According to the ELN risk stratification, patients were classified as favorable, intermediate or adverse risk (23%, 38% and 39% of patients, respectively)
• There was no significant difference in the achievement of complete remission (CR) between patients receiving ICE and sHD: 61% vs 71% respectively, P = 0.23
• There was no significant difference in early death rate between the ICE and sHD: 10.6% vs 12% respectively, P = 0.96
• 5-years overall survival (OS) and disease-free survival (DFS) were 29% and 32% respectively
• Survival in patients grouped according to ELN-risk stratification, favorable, intermediate and adverse groups respectively
  • 5-years OS: 68% vs 24% vs 9%, P < 0.0001
  • 3-years DFS: 73% vs 29% vs 12%, P < 0.0001 
• Survival according to the presence or absence of a MDS/MPN signature at diagnosis, respectively
  • 5-years OS: 11% vs 41%, P = 0.0001
  • 3-years DFS: 12% vs 49%, P < 0.0001
• Survival in patients who underwent allogeneic stem cell transplantation (SCT) in first CR compared to those that did not, respectively
  • 5-years OS: 57% vs 33%, P = 0.0321
  • 5-year DFS: 53% vs 27%, P = 0.0436

The speaker highlighted that risk stratification according to the ELN 2017 and genetic definition of sAML inform prognosis in older patients with AML. In addition, older AML patients with favorable risk features according to ELN benefit from standard chemotherapy.

Accurate genetic characterization is mandatory to identify older patients with AML who benefit from the available treatments and to individualize treatment selection. In high-risk, ≥ 60 years old AML patients with good performance status, alloHSCT was effective and the speaker recommends it to be considered as the most effective post consolidation treatment.