Early Detection of WT1 Minimal Residual Disease Predicts Outcomes in AML

Using Wilms’ tumor gene (WT1) expression as a marker for minimal residual disease (MRD) in patients with acute myeloid leukemia (AML) is a powerful prognostic factor in treatment selection, according to a study of 713 patients with AML.

Researchers led by Dr. Juliette Lambert of the University Paris-Saclay, Le Chesnay, France, evaluated the prognostic value of post-induction WT1 MRD level, plus the interaction between post-induction WT1 MRD response and the effect of HCT in first complete remission (CR).

Patients were age 18 to 59 years, and 539 patients (75.6%) had an overexpression of WT1 at diagnosis.

After induction, MRD levels were assessed using cDNA-based real-time quantitative polymerase chain reaction (PCR). Occurrence of a WT1 MRD ratio >2.5% in the marrow or >0.5% in peripheral blood was categorized as positive MRD (MRD+), while a ratio under these thresholds was defined as negative MRD (MRD-).

Among the 539 WT1+ patients at diagnosis, 473 achieved CR (87.7%), and of those, 279 patients were MRD- and 60 were MRD+.

Outcomes at 4 years post-induction are shown below.

 Outcome MRD-
 HR (95% CI) p-value
 Overall survival 71.6% 43.3% 2.34 (1.56-3.51) <0.001
 Relapse-free survival 60.9% 24.9% 2.69 (1.89-3.83) <0.001
 Relapse 36.5% 69.2% 2.88 (1.93-4.29) <0.001

When adjusted for age, cytogenetics, NPM1 mutation status and FLT3-ITD status, MRD remained independently associated with relapse incidence (HR, 2.15 [1.41-3.29]; p<0.001).

The role of MRD in allogeneic transplantation

The researchers then analyzed the role of HCT in 254 patients with intermediate-/unfavorable-risk AML and available post-induction WT1 MRD evaluation (199 MRD-, 55 MRD+). HCT was performed in 155 patients. Overall, both MRD and HCT were independent prognostic factors.

In these patients, HCT significantly improved the cumulative incidence of relapse (HR, 0.33 [0.22-0.51]; p<0.001) and RFS (HR, 0.53 [0.37-0.76]; p=0.001).

Dr. Lambert and her colleagues concluded that because early WT1 MRD response retains its prognostic value among patients independently of HCT in first CR, this may help risk-stratify treatment choices for patients with WT1 more accurately.

Lambert J, et al. Abstract oral presentation, 2017 ASH annual meeting

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