By Lynda Williams, medwireNews Reporter
medwireNews: Research demonstrates a dose-dependent correlation between measurable residual disease (MRD) and the likelihood of relapse and poor overall survival (OS) among adults with acute myeloid leukaemia (AML) who achieve complete remission (CR) before undergoing allogeneic haematopoietic cell transplantation (HCT).
Although persistent FLT3 internal tandem duplication (ITD) has been shown to be prognostic in adults with this form of AML, the level of MRD required to impact clinical outcome was unknown, explain Christopher Hourigan (Virigina Tech Fralin Biomedical Research Institute, Washington, DC, USA) and co-workers.
They report in JAMA Oncology findings for 537 patients who participated in the Pre-MEASURE study and had DNA sequencing performed on blood samples at the time of their first remission and before undergoing allogeneic HCT. Around half (55.1%) of the patients were women and the median age was 55.6 years.
The FLT3-ITD MRD next-generation sequencing (NGS) assay used was able to detect a variant allele fraction (VAF) of above 0.005% and the findings were compared with results previously reported using a multiplex polymerase chain reaction-based targeted NGS assay able to detect variants to 0.01% VAF.
Over a median follow-up of 35.9 months, 32.2% of patients relapsed, at a median of 5.2 months, and 40.8% of patients died.
Overall, 33.0% of patients had detectable FLT3-ITD at any level and were at significantly increased risk of relapse and a significantly poorer OS compared with patients who tested negative for FLT3-ITD.
In multivariable competing risks regression analysis adjusting for baseline clinical characteristics, the risk of relapse was highest among patients who had MRD with a VAF of 0.1% or above (hazard ratio [HR]=8.15), followed by those with a VAF of 0.01% or above but less than 0.1% (HR=4.62). The HR for relapse then fell to 2.30 for patients with a VAF of at least 0.001% but less than 0.01% and 2.16 for those with a VAF of between 0% and 0.001%.
The corresponding HRs for mortality were 3.87, 3.45, 1.70 and 1.72, report Hourigan and co-authors.
The researchers also found that FLT3-ITD MRD-positive patients who received a reduced intensity conditioning regimen without melphalan or a nonmyeloablative conditioning regimen were more like to experience relapse or die than those who received a higher intensity regimen, with HRs of 2.01 and 1.89, respectively.
“This study of the Pre-MEASURE cohort provides strong justification for NGS-based AML MRD clinical testing for persistent FLT3-ITD prior to allogeneic HCT”, say Hourigan et al.
“An MRD definition of VAF of 0.01% or greater identified patients with very high risk of relapse and poor OS when treated according to the current standard of care.”
News stories are provided by medwireNews, which is an independent medical news service provided by Springer Healthcare Ltd. © 2024 Springer Healthcare Ltd, part of the Springer Nature Group
JAMA Oncol 2024; doi:10.1001/jamaoncol.2024.0985