Is NPM1 MRD Status Prognostic in Patients with AML Receiving Venetoclax-Based Therapy?

By Cecilia Brown - Last Updated: September 21, 2023

NPM1 measurable residual disease (MRD) provides “valuable prognostic information” in patients with NPM1-mutated acute myeloid leukemia (AML) who attain remission with venetoclax-based combination therapies, according to a recent study.

Jad Othman, MBBS, of the University of Sydney and colleagues conducted the study because the assessment of MRD is “strongly prognostic in patients with NPM1-mutated AML treated with intensive chemotherapy, however there are no data regarding its utility in venetoclax-based nonintensive therapy, despite high efficacy in this genotype.”

The analyzed the prognostic impact of NPM1 MRD in an international real-world cohort that included 76 patients with previously untreated NPM1-mutated AML. All patients in the study achieved a complete remission (CR) or CR with incomplete hematologic recovery after receiving venetoclax and hypomethylating agents or low-dose cytarabine.

The researchers reported that 58% of patients achieved MRD negativity in bone marrow. The cumulative rate of MRD negativity in bone marrow was 25% at the end of cycle two, 47% at the end of cycle four, and 50% at the end of cycle six. Patients who achieved MRD negativity by the end of cycle four had a two-year overall survival (OS) rate of 84%. The two-year OS rate was 46% for those who were MRD positive at the end of cycle four.

Multivariable analyses showed MRD negativity was the “strongest prognostic factor,” according to Dr. Othman and colleagues. Of the 76 patients in the study, 22 electively stopped therapy while in MRD-negative remission after a median of eight cycles with a two-year treatment-free remission rate of 88%.

“In patients with NPM1-mutated AML attaining remission with venetoclax combination therapies, NPM1 MRD provides valuable prognostic information,” Dr. Othman and colleagues concluded.


Othman J, Tiong IS, O’Nions J Dr, et al. Molecular MRD is strongly prognostic in patients with NPM1-mutated AML receiving venetoclax-based non-intensive therapy. Blood. 2023. doi:10.1182/blood.2023021579

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