MRD by qPCR prognostic of outcomes in venetoclax-treated NPM1-mutated AML 

Measurable/minimal residual disease (MRD) assessment by qPCR was strongly associated with clinical outcomes in patients with NPM1-mutated acute myeloid leukaemia (AML) who achieved complete remission (CR)/complete remission with incomplete recovery count (CRi) on venetoclax combination therapies.

“Flow cytometric MRD assessment is prognostic of clinical outcomes in venetoclax combinations-treated patients with various AML mutations,” stated Mr Jad Othman (Guy’s and St Thomas’ NHS Foundation Trust, UK) [1,2]. The presented study aimed to determine whether MRD by qPCR is prognostic of clinical outcomes in patients with NPM1-mutated AML who achieved CR/CRi in the real-world on venetoclax plus either low-dose cytarabine or a hypomethylating agent.

In a cohort of 55 patients, the best MRD response rates in the first 6 months of therapy were as follows: MRD undetectable (46%), ≥4 log reduction (19%), <4 log reduction (35%). After a median follow-up of 24.3 months, the deepest MRD reduction within the first 6 months was strongly related to overall survival (OS; P=0.00027) and event-free survival (EFS; P<0.0001), favouring those with undetectable MRD over the other subgroups (see Figure). Mr Othman added that an MRD cut-off of <0.005 NPM1 copies/100 ABL was the best discriminator for OS (P<0.0001) and EFS (P<0.0001). Finally, it was noted that peripheral blood MRD, although less sensitive than bone marrow MRD, may be adequately sensitive to predict clinical outcomes.

Figure: Deepest MRD reduction within the first 6 months is strongly associated with outcomes [2]



OS, overall survival; EFS, event-free survival.

1. Pratz KW, et al. J Clin Oncol. 2022;40(8):855–865.
2. Othman J, et al. Molecular MRD Assessment Is Strongly Prognostic in Patients with NPM1¬ Mutated AML Receiving Venetoclax Based Non-Intensive Therapy. Abstract 840, ASH 64^th Annual Meeting, 10–13 December 2022, New Orleans, LA, USA.

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Posted on 20 February 2023