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. 2021 Dec 14;5(23):5107-5111.
doi: 10.1182/bloodadvances.2021005455.

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

Ing S Tiong  1   2 , Richard Dillon  3   4 , Adam Ivey  1   5 , James A Kuzich  6 , Nisha Thiagarajah  2   7 , Kirsty M Sharplin  8 , Chung Hoow Kok  9 , Aditya Tedjaseputra  10 , James P Rowland  11 , Carolyn S Grove  12 , Emad Abro  11 , Jake Shortt  10   13 , Devendra K Hiwase  8 , Ashish Bajel  2   7 , Nicola E Potter  3 , Matthew L Smith  14 , Claire J Hemmaway  15 , Abin Thomas  16 , Amanda F Gilkes  17 , Nigel H Russell  4 , Andrew H Wei  1   5
Affiliations

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

Ing S Tiong et al. Blood Adv. .

Erratum in

Abstract

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 (CRMRD-; 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.

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Figures

Figure 1.
Figure 1.
Clinical impact of patients with detectable NPM1mut MRD at completion of chemotherapy. Conversion from initial state (molecular persistence) to different outcomes censored after the first event, either sustained CRMRD−, molecular failure, or morphologic relapse without preceding molecular failure. The proportion of patients in each category at specified time points are listed in the table below.
Figure 2.
Figure 2.
Kaplan-Meier survival curves. (A) Event-free survival and (B) overall survival according to FLT3-ITD status at diagnosis and at EOT NPM1mut reduction (4.4-log) from baseline.
See this image and copyright information in PMC

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