Prognostic Role of Multiparameter Flow Cytometry-Based Measurable Residual Disease Assessment in Acute Myeloid Leukemia Patients with FMS3-like Tyrosine Kinase-3 Internal Tandem Duplication (FLT3-ITD)

Introduction Measurable residual disease (MRD) monitoring is predictive in acute myeloid leukemia (AML). Assessment of FMS3-like tyrosine kinase-3 in-frame internal tandem duplications (FLT3-ITD) is usually performed at diagnosis by polymerase chain reaction (PCR). Due to its relative lower sensitiv...

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Published in:Blood 2023-11, Vol.142 (Supplement 1), p.1595-1595
Main Authors: Lucero, Josephine Anne, Bankar, Aniket, Davidson, Marta Beata, Richard-Carpentier, Guillaume, Schimmer, Aaron D., Schuh, Andre C., Maze, Dawn C., Yee, Karen, Minden, Mark D., Chan, Steven M., Mattsson, Jonas, Kumar, Rajat, Gupta, Vikas, Capo-Chichi, Jose-Mario, Stockley, Tracy, Sibai, Hassan, Tierens, Anne Maria, Kim, Dennis Dong Hwan
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Language:English
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Summary:Introduction Measurable residual disease (MRD) monitoring is predictive in acute myeloid leukemia (AML). Assessment of FMS3-like tyrosine kinase-3 in-frame internal tandem duplications (FLT3-ITD) is usually performed at diagnosis by polymerase chain reaction (PCR). Due to its relative lower sensitivity of 2%, FLT3-ITD PCR is not routinely used during response assessment. Next-generation sequencing is similarly limited by technical difficulties in capturing tandem duplications using the short base pair-based sequencing method. Long base pair-based sequencing has been reported, but its use is limited by financial restrictions. Multiparameter flow cytometry (MFC) can be a useful tool for MRD monitoring in this AML subtype until such time that molecular techniques for detecting FLT3-ITD MRD are optimized. Patients and methods The study evaluated the outcomes of FLT3-ITD mutated AML patients diagnosed and treated from 2018 to 2022 at Princess Margaret Cancer Centre. We compared outcomes according to MFC-MRD post-induction and FLT3-ITD allele frequency (AF) status at diagnosis. MRD cut-off was 0.1%. Data were locked as of June 30, 2023. Clinical outcomes evaluated include overall survival (OS) and relapse-free survival (RFS). The cumulative incidence of relapse (CIR) and non-relapse mortality (NRM) were calculated considering competing risk. The Kaplan-Meier method using a log-rank test and a multivariate Cox proportional hazard model was used for analyses, while the Gray test and Fine-Grey model were used for uni- and multivariate analysis for CIR and NRM. Results A total of 111 patients with a mean age of 63.5 years were included, of whom 90 received treatment. Secondary AML accounted for 12.7% of patients. Risk stratification according to European LeukemiaNet (ELN) 2022 was favorable in 2 (1.8%), intermediate in 67 (60.4%), and adverse in 42 patients (37.8%). Nucleophosmin 1 (NPM1) co-mutation was observed in 55 patients (49.5%). Seventy-nine patients (87.8%) could be assessed for overall response, including 69 (76.7%) who achieved complete remission (CR) or CR with incomplete count recovery (CRi). Of these, 54 achieved first CR/CRi (CR1) with 1 induction cycle. MFC-MRD data were available in 61 patients, of whom 44 (72.1%) were MRD negative, while 17 (27.9%) were MRD positive. With a median follow-up of 437 days, 50 patients (45%) were still alive. Median OS and RFS were 3.42 years and 1.05 years, respectively. Among patients who achieved CR1, post-induction
ISSN:0006-4971
1528-0020
DOI:10.1182/blood-2023-190694