Assessment of minimal residual disease in standard-risk AML (NPM1-mutated AML within the NCRI AML17 trial): trial

Assessment of minimal residual disease in standard-risk AML (NPM1-mutated AML within the NCRI AML17 trial)

Phase observationalN = 346

Population

Patients with NPM1-mutated AML who had received intensive treatment in the AML17 trial.

Design

Cohort analysis within the National Cancer Research Institute AML17 trial: reverse-transcriptase quantitative PCR for NPM1-mutated transcripts in 2569 samples from 346 patients, with targeted 51-gene sequencing of diagnosis (223) and relapse (49) samples and validation in an independent cohort. No treatment comparison.

Arms

NPM1 transcripts not persistent (control): No persisting NPM1-mutated transcripts in blood after the second chemotherapy cycle (reference group)
NPM1 transcripts persistent (experimental): Persisting NPM1-mutated transcripts in blood after the second chemotherapy cycle (15% of patients)

People

Ivey A, UK National Cancer Research Institute AML Working Group

Relapse riskHR 4.80 (95% CI 2.95–7.80)Δ 36-month Relapse risk+52 pointsOSHR 4.38 (95% CI 2.57–7.47)Δ OS−51 points

Show the numbers

Results reported for Assessment of minimal residual disease in standard-risk AML (NPM1-mutated AML within the NCRI AML17 trial)
Endpoint	Analysis	NPM1 transcripts persistent	NPM1 transcripts not persistent	Effect
Relapse riskPatients with NPM1-mutated AML, MRD status in blood after the second chemotherapy cycle	primaryIvey 2016	82% at 3 y	30% at 3 y	HR 4.80 (95% CI 2.95–7.80)P<0.001Prognostic association in a cohort; the comparison is MRD-positive versus MRD-negative, not a randomised treatment comparison.
OSPatients with NPM1-mutated AML, MRD status in blood after the second chemotherapy cycle	primaryIvey 2016	24%	75%	HR 4.38 (95% CI 2.57–7.47)P<0.001Survival rate as published; the abstract does not state the time point. In multivariate analysis the hazard ratio for death with MRD present was 4.84 (95% CI 2.57 to 9.15; P<0.001).

Results reported for Assessment of minimal residual disease in standard-risk AML (NPM1-mutated AML within the NCRI AML17 trial)
Endpoint	Analysis	NPM1 transcripts persistent	NPM1 transcripts not persistent	Effect
Relapse riskPatients with NPM1-mutated AML, MRD status in blood after the second chemotherapy cycle	primaryIvey 2016	82% at 3 y	30% at 3 y	HR 4.80 (95% CI 2.95–7.80)P<0.001Prognostic association in a cohort; the comparison is MRD-positive versus MRD-negative, not a randomised treatment comparison.
OSPatients with NPM1-mutated AML, MRD status in blood after the second chemotherapy cycle	primaryIvey 2016	24%	75%	HR 4.38 (95% CI 2.57–7.47)P<0.001Survival rate as published; the abstract does not state the time point. In multivariate analysis the hazard ratio for death with MRD present was 4.84 (95% CI 2.57 to 9.15; P<0.001).

Hazard ratio (95% CI) by endpoint. Values below 1 favour the experimental arm.

Data table

Endpoint	HR	95% CI
Relapse risk	4.8	2.95–7.8
OS	4.38	2.57–7.47

Appears in

2016 Measurable residual disease in AML: prognostic value and monitoring

Sources

Ivey A, Hills RK, Simpson MA, Jovanovic JV, Gilkes A, Grech A, et al. Assessment of Minimal Residual Disease in Standard-Risk AML. N Engl J Med. 2016;374(5):422-33.
PubMed DOI