Photo by William Weinert
A test measuring minimal residual disease (MRD) can help predict relapse in patients with acute myeloid leukemia (AML), according to a study published in NEJM.
Investigators used the test to detect MRD in samples from patients with NPM1-mutated AML who were deemed standard-risk by conventional methods.
The team said the presence of MRD after treatment provided powerful prognostic information independent of other risk factors.
“What we have been able to identify is a group of patients who otherwise would be thought to do quite well, who, in fact, have a very poor prognosis, and who are not well served currently,” said study author Robert Hills, DPhil, of Cardiff University School of Medicine in the UK.
“This opens up the exciting prospect that we can do the same for other groups of patients as well.”
For this study, Dr Hills and his colleagues used a reverse-transcriptase quantitative polymerase-chain-reaction assay to detect MRD in 2569 samples (902 bone marrow samples and 1667 peripheral blood samples) from 346 patients with NPM1-mutated AML.
The patients had received 2 cycles of chemotherapy as part of the National Cancer Research Institute AML17 trial. They were treated at centers in the UK, Denmark, and New Zealand. All patients were shown to be at standard risk of relapse using conventional tests.
The investigators found that NPM1-mutated transcripts persisted in the blood of 15% of patients after the second cycle of chemotherapy.
This finding was associated with a greater risk of relapse after 3 years of follow-up.
Eighty-two percent of patients with NPM1-mutated transcripts had relapsed within 3 years, compared to 30% of patients who had no detectable NPM1. The hazard ratio was 4.80 (P<0.001).
Patients with traces of NPM1 also had a lower rate of survival—24%, compared to 75% for patients without detectable NPM1. The hazard ratio was 4.38 (P<0.001).
In multivariate analysis, the presence of MRD was the only significant prognostic factor for relapse or death. The hazard ratios were 5.09 and 4.84, respectively (P<0.001 for both).
The investigators validated these findings in a cohort of 91 patients with NPM1-mutated AML.
The presence of MRD in the blood of these patients was associated with a higher cumulative incidence of relapse—70% vs 31% (P=0.001)—and a lower rate of survival—40% vs 87% (P=0.001)—at 2 years.
The investigators also found that, with sequential monitoring of MRD, a rising level of NPM1-mutated transcripts could predict relapse.
“Conventional methods for guiding treatment for this aggressive type of leukemia are inadequate,” said study author David Grimwade, PhD, of King’s College London in the UK.
“The MRD test is an invaluable tool to assess treatment response and identify those patients for whom chemotherapy is not sufficient and require stem cell transplantation or new treatments.”
