General AML

ASH 2018 | MRD status after induction therapy in older adults with acute myeloid leukemia

At the  60th American Society of Hematology Annual Meeting & Exposition, James M. Foran from Mayo Clinic Florida, Jacksonville, FL, presented data from the ECOG-ACRIN (E-A) E2906 phase III trial, which is prospectively assessing a planned assessment of measurable residual disease (MRD) status after induction therapy in older adults with acute myeloid leukemia (AML).

In this E-A E2906 phase III trial, patients with AML were randomized 1:1 to receive either 7 + 3 consisting of daunorubicin (60 mg/m2) induction, with 2 cycles of intermediate-dose cytarabine (Ara-C; 1.5 g/m2 x 12 doses; 6 doses if age ≥ 70) consolidation (Arm A); or single agent clofarabine (CLO) induction and consolidation (2 cycles) (Arm B). With a median follow-up of 47.8 months, 43.4% (297/685) of evaluable patients achieved complete remission (CR) or CR with incomplete complete blood count (CBC) recovery (CRi).  

For the MRD analysis, diagnostic and remission bone marrow or peripheral blood samples were analyzed using multiparameter flow cytometry. MRD-positive (MRD+) was defined as ≥ 0.1%. Remission MRD samples were only available for 147 CR/CRi patients (49.5%).

Key findings:
  • Fifty-eight patients of the 147 evaluable CR/CRi patients achieved MRD-negative (MRD-) status
    • Patients achieving MRD-negativity in Arm A and Arm B were 40.7% and 47.9%, respectively: P = 0.74
  • MRD+ status at CR/CRi associated significantly with inferior overall survival (OS), P = 0.031
  • MRD+ status at CR/CRi associated significantly with inferior disease-free survival (DFS), P = 0.02
    • MRD+ status at CR/CRi associated significantly with inferior DFS in Arm B (P = 0.005) but not arm A (P = 0.41)

The speaker, James Foran, noted that “MRD+ ≥ 0.1% is common (60.5%) after induction therapy in older adults with AML and it significantly associated with inferior OS and DFS in first CR/CRi.”

In conclusion, James Foran noted that the results from this study “differs strikingly from younger AML, and suggests that intensified Ara-C may abrogate the adverse impact of MRD in older patients in CR.” He further added that “these results strongly support the incorporation of centralized MRD at the time of remission into future studies to guide optimal post-remission strategies in older patients with AML.”

References
  1. Foran J. M. et al. Minimal residual disease (MRD) at time of complete remission is commonly detected in acute myeloid leukemia (AML) patients age ≥60 years and significantly impacts outcome based on post-remission treatment strategies: prospective analysis of ECOG-ACRIN (E-A) E2906 phase III trial. 2018 Dec 2; Oral Abstract #437: 60th ASH Annual Meeting and Exposition, San Diego, CA.
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