Molecular minimal residual disease in acute myeloid leukemia: trial

Molecular minimal residual disease in acute myeloid leukemia

Phase observationalN = 482

Population

Patients aged 18 to 65 years with newly diagnosed AML.

Design

Observational analysis (the abstract says only 'a study involving patients' and names no source trial): targeted next-generation sequencing at diagnosis and after induction therapy (in complete remission); end points were 4-year relapse rate, relapse-free survival and overall survival. At least one mutation was detected at diagnosis in 430 of 482 patients; persisting mutations were then classified, with persistent DTA mutations (DNMT3A, TET2, ASXL1) analysed separately.

Arms

No persisting non-DTA mutation (control): No molecular MRD detected in complete remission after exclusion of persistent DTA mutations (reference group)
Persisting non-DTA mutation (experimental): Molecular MRD detected in complete remission after exclusion of persistent DTA mutations

People

Jongen-Lavrencic M

Relapse riskHR 2.14Δ 48-month Relapse risk+23.5 pointsRFSHR 1.92Δ 48-month RFS−21.5 pointsOSHR 2.06Δ 48-month OS−24.2 points

Show the numbers

Results reported for Molecular minimal residual disease in acute myeloid leukemia
Endpoint	Analysis	Persisting non-DTA mutation	No persisting non-DTA mutation	Effect
Relapse riskPatients in complete remission, persistent DTA mutations excluded	primaryJongen-Lavrencic 2018	55.4% at 4 y	31.9% at 4 y	HR 2.14P<0.001Prognostic association in a cohort. The abstract gives no confidence intervals for these hazard ratios.
RFSPatients in complete remission, persistent DTA mutations excluded	primaryJongen-Lavrencic 2018	36.6% at 4 y	58.1% at 4 y	HR 1.92P<0.001
OSPatients in complete remission, persistent DTA mutations excluded	primaryJongen-Lavrencic 2018	41.9% at 4 y	66.1% at 4 y	HR 2.06P<0.001Multivariate analysis, as published: persistence of non-DTA mutations in complete remission had independent prognostic value for relapse (HR 1.89; P<0.001), relapse-free survival (HR 1.64; P=0.001) and overall survival (HR 1.64; P=0.003).

Results reported for Molecular minimal residual disease in acute myeloid leukemia
Endpoint	Analysis	Persisting non-DTA mutation	No persisting non-DTA mutation	Effect
Relapse riskPatients in complete remission, persistent DTA mutations excluded	primaryJongen-Lavrencic 2018	55.4% at 4 y	31.9% at 4 y	HR 2.14P<0.001Prognostic association in a cohort. The abstract gives no confidence intervals for these hazard ratios.
RFSPatients in complete remission, persistent DTA mutations excluded	primaryJongen-Lavrencic 2018	36.6% at 4 y	58.1% at 4 y	HR 1.92P<0.001
OSPatients in complete remission, persistent DTA mutations excluded	primaryJongen-Lavrencic 2018	41.9% at 4 y	66.1% at 4 y	HR 2.06P<0.001Multivariate analysis, as published: persistence of non-DTA mutations in complete remission had independent prognostic value for relapse (HR 1.89; P<0.001), relapse-free survival (HR 1.64; P=0.001) and overall survival (HR 1.64; P=0.003).

Appears in

2016 Measurable residual disease in AML: prognostic value and monitoring

Sources

Jongen-Lavrencic M, Grob T, Hanekamp D, Kavelaars FG, Al Hinai A, Zeilemaker A, et al. Molecular Minimal Residual Disease in Acute Myeloid Leukemia. N Engl J Med. 2018;378(13):1189-1199.
PubMed DOI