Sequential molecular measurable residual disease (MRD) testing and monitoring led to a survival benefit among younger patients with acute myeloid leukemia (AML) and NPM1 and FLT3-ITD mutations, according to the results of a study published in The Lancet Haematology.
Patients with both mutations who received MRD monitoring demonstrated a 47% improvement in the risk of death compared with those who were not monitored for MRD, as physicians were able to adjust treatment decisions according to the MRD results.
“[AML] is the most aggressive form of blood cancer, so knowing early that a patient’s cancer is going to relapse is crucial for planning their treatment. We hope that these tests become part of routine care for this type of cancer...and ultimately improve long-term survival rates for patients,” said senior study author Richard Dillon, FRCPath, Clinical Senior Lecturer in Cancer Genetics at King’s College London.
Study Methods and Results
The study authors analyzed patients from across two UK trials (AML17 and AML19) who were between 16 and 60 years old with newly diagnosed AML. Patients were screened for molecular markers and were randomly assigned 2:1 to undergo MRD monitoring or not. Monitoring lasted during treatment and for 3 years thereafter. Physicians were able to adjust treatment according to the MRD results in the monitoring cohort.
The primary endpoint of the study was overall survival in all patients, but a subgroup analysis looked at outcomes by molecular groups, including those with NPM1 mutations with FLT3-ITD mutations, those with NPM1 but no FLT3-ITD, and patients with fusion gene transcripts.
The 3-year overall survival rate among all patients was 70% in the MRD monitoring cohort and 73% in the no-monitoring cohort (hazard ratio [HR] = 1.11; 95% confidence interval [CI] = 0.83–1.49; P = .25).
Patients with both NPM1 and FLT3-ITD mutations showed a 3-year overall survival rate of 69% with MRD monitoring vs 58% in the no-monitoring cohort (HR = 0.53; 95% CI = 0.31–0.91; P = .021).
Those with NPM1 mutations but no FLT3-ITD mutations had 3-year overall survival rates of 69% with monitoring and 78% without (HR = 1.56; 95% CI = 0.96–2.52), and patients with fusion gene transcripts had 3-year overall survival rates of 72% and 77%, respectively (HR = 1.28; 95% CI = 0.80–2.18).
“There is still so much to learn about how best to treat this fast-moving form of cancer. We hope our research offers a new approach to detecting if a patient is at risk of relapse and offers hope to patients suffering from this disease,” stated co-author Nigel Russell, FRCPath, an Honorary Consultant at Guy’s and St Thomas’ NHS Foundation Trust.
Disclosure: For full disclosures of the study authors, visit thelancet.com.
