Detection of Minimal Residual Disease Predicts Outcomes, Can Guide Strategies in AML

Minimal residual disease (MRD) in patients with acute myeloid leukemia (AML) can be a powerful predictor of outcomes, according to research that analyzed detection of MRD presented at the 60th American Society of Hematology Annual Meeting & Exposition.

The first study described an assessment of immunophenotypic MRD in patients with AML. The median age of the 310 patients was 33 years. They explained that detecting MRD early in treatment, but after chemotherapy, “is highly predictive of outcome and offers a window of opportunity to intensify treatment and prevent relapse as seen in [acute lymphoblastic leukemia].”

The patients in the study all received standard induction chemotherapy, after which MRD testing was done. The samples were processed using a 2-tube 10-color assay. Patients were classified into 3 groups: favorable (35.1%), intermediate (52.5%), and poor (12.2%) cytogenetic risk.

The researchers also detected the presence of FLT3-ITD, NPM1, and CEBPA mutations in 21.9%, 29.0%, and 7.7% of patients, respectively. In the 298 patients for which postinduction MRD was assessed, 114 (38.3%) had detectable residual disease. Testing was also done after first consolidation chemotherapy in 186 patients. Of these patients, only 49 (26.4%) were MRD positive.

Risk stratification was, as expected, predictive of overall survival (OS) and relapse-free survival (RFS). For the full group, the 3-year median RFS was 18.7 months and OS was 59.0%. Patients with poor risk cytogenetics had a median OS of 14.6 months compared with median survival not being met and a median RFS of 9.3 months compared with 18.6 months.

When MRD was present at the postinduction time period, patients had an inferior OS and RFS compared with patients who had negative MRD. Furthermore, patients who were positive for MRD at the end of consolidation chemotherapy had worse OS and RFS than patients who were negative for MRD.

Based on the results, the researchers recommended incorporating MRD detection into routine treatment algorithms in patients with AML.

“Our data demonstrates that MRD by flow cytometry at end of induction as well as consolidation are important prognostic factors together with known factors such as high-risk cytogenetics,” they concluded.

Reference

Subramanian PG, Kakirde C, Kodgule R, et al. Immunophenotypic assessment of minimal residual disease in younger acute myeloid leukemia patients is highly predictive of outcome. Presented at: 60th American Society of Hematology Annual Meeting & Exposition; December 1, 2018; San Diego, CA. Abstract 1498.