Clinical impact of NPM1-mutant molecular persistence after chemotherapy for acute myeloid leukemia

TY - JOUR

T1 - Clinical impact of NPM1-mutant molecular persistence after chemotherapy for acute myeloid leukemia

AU - Tiong, Ing S.

AU - Dillon, Richard

AU - Ivey, Adam

AU - Kuzich, James A.

AU - Thiagarajah, Nisha

AU - Sharplin, Kirsty M.

AU - Kok, Chung Hoow

AU - Tedjaseputra, Aditya

AU - Rowland, James P.

AU - Grove, Carolyn S.

AU - Abro, Emad

AU - Shortt, Jake

AU - Hiwase, Devendra K.

AU - Bajel, Ashish

AU - Potter, Nicola E.

AU - Smith, Matthew L.

AU - Hemmaway, Claire J.

AU - Thomas, Abin

AU - Gilkes, Amanda F.

AU - Russell, Nigel H.

AU - Wei, Andrew H.

N1 - Publisher Copyright: © 2021 American Society of Hematology. All rights reserved.

PY - 2021/12/14

Y1 - 2021/12/14

N2 - Monitoring of NPM1 mutant (NPM1mut) measurable residual disease (MRD) in acute myeloid leukemia (AML) has an established role in patients who are treated with intensive chemotherapy. The European LeukemiaNet has defined molecular persistence at low copy number (MP-LCN) as an MRD transcript level ,1% to 2% with a ,1-log change between any 2 positive samples collected after the end of treatment (EOT). Because the clinical impact of MP-LCN is unknown, we sought to characterize outcomes in patients with persistent NPM1mut MRD after EOT and identify factors associated with disease progression. Consecutive patients with newly diagnosed NPM1mut AML who received $2 cycles of intensive chemotherapy were included if bone marrow was NPM1mut MRD positive at the EOT, and they were not transplanted in first complete remission. One hundred patients were followed for a median of 23.5 months; 42% remained free of progression at 1 year, either spontaneously achieving complete molecular remission (CRMRD2; 30%) or retaining a low-level NPM1mut transcript (12% for $12 months and 9% at last follow-up). Forty percent met the criteria for MP-LCN. Preemptive salvage therapy significantly prolonged relapse-free survival. Risk factors associated with disease progression were concurrent FLT3-internal tandem duplication at diagnosis and suboptimal MRD response (NPM1mut reduction ,4.4-log) at EOT.

AB - Monitoring of NPM1 mutant (NPM1mut) measurable residual disease (MRD) in acute myeloid leukemia (AML) has an established role in patients who are treated with intensive chemotherapy. The European LeukemiaNet has defined molecular persistence at low copy number (MP-LCN) as an MRD transcript level ,1% to 2% with a ,1-log change between any 2 positive samples collected after the end of treatment (EOT). Because the clinical impact of MP-LCN is unknown, we sought to characterize outcomes in patients with persistent NPM1mut MRD after EOT and identify factors associated with disease progression. Consecutive patients with newly diagnosed NPM1mut AML who received $2 cycles of intensive chemotherapy were included if bone marrow was NPM1mut MRD positive at the EOT, and they were not transplanted in first complete remission. One hundred patients were followed for a median of 23.5 months; 42% remained free of progression at 1 year, either spontaneously achieving complete molecular remission (CRMRD2; 30%) or retaining a low-level NPM1mut transcript (12% for $12 months and 9% at last follow-up). Forty percent met the criteria for MP-LCN. Preemptive salvage therapy significantly prolonged relapse-free survival. Risk factors associated with disease progression were concurrent FLT3-internal tandem duplication at diagnosis and suboptimal MRD response (NPM1mut reduction ,4.4-log) at EOT.

UR - https://www.scopus.com/pages/publications/85121721973

U2 - 10.1182/bloodadvances.2021005455

DO - 10.1182/bloodadvances.2021005455

M3 - Article

C2 - 34555849

AN - SCOPUS:85121721973

SN - 2473-9529

VL - 5

SP - 5107

EP - 5111

JO - Blood Advances

JF - Blood Advances

ER -