Minimal residual disease prognostic in standard-risk AML

Blood cancers

By Tony James

21 Jan 2016

The presence of minimal residual disease evidenced by NPM1-mutated transcripts provides powerful prognostic information in patients with standard-risk acute myeloid leukaemia, potentially changing current approaches to risk stratification and treatment selection.

A report in the New England Journal of Medicine described AML patients included in the National Cancer Institute AML17 trial of intensive therapy who had completed two cycles of induction chemotherapy. A 51 gene panel was used to perform targeted sequencing of 233 samples obtained at the time of diagnosis and 49 samples obtained at the time of relapse.

Molecular profiling confirmed the heterogeneity of AML, identifying more than 150 subgroups of patients. Minimal residual disease (MRD) status, however, was more informative.

“Persistence of NPM1-mutated transcripts in blood was present in 15% of the patients after the second chemotherapy cycle and was associated with a greater risk of relapse after 3 years of follow up [82% vs 30%] than was an absence of such transcripts,” the researchers said.

Patients with MRD also had a lower rate of survival (24% vs 75%).

MRD was the only independent prognostic factor for death identified in the analysis.

“Its presence was superior to the baseline diagnostic molecular genetic markers that are currently used to guide decisions with respect to stem-cell transplantation,” they said.

The analysis was prompted by uncertainty about the role of transplantation in patients with cytogenetically standard-risk AML, which affected about 50% of younger adult patients. About half of that group had an NPM1 mutation.

“There is growing interest in whether prognostication can be improved through more extensive molecular profiling that capitalises on advances in sequencing technology,” the researchers said.

An editorial commented that MRD was well established as a prognostic marker in acute lymphoblastic leukaemia but its role in AML had been unclear.

“AML has a greater molecular heterogeneity and the routine assessment of MRD has not been as quickly adopted,” it said.

The editorial said the clinical implications of these new findings were substantive and could change the approach to risk stratification.

Patients previously classified as being at standard or low risk might, in fact, be at high risk and would benefit from transplantation. Conversely, some patients previously classified at high risk on current criteria who had no evidence of MRD might be able to avoid transplantation, but prospective studies were needed to test these theories

Already a member?

Login to keep reading.

Email me a login link