Unmasking Hidden Acute Myeloid Leukemia: The Power of Measurable Residual Disease Detection with Multiparameter Flow Cytometry

In 2024, the American Cancer Society predicts 20,800 new cases of acute myeloid leukemia (AML) and approximately 11,220 deaths [1]. AML patients require monitoring after treatment, so healthcare specialists can predict relapses as early as possible. A key weapon in the treatment arsenal is early detection of measurable residual disease (MRD) because MRD patients “have higher relapse rates and worse survival than similar patients testing negative” [2]. Clinicians have three methods to determine MRD: multiparameter flow cytometry (MFC), quantitative polymerase chain reaction (qPCR), and next-generation sequencing (NGS) [3].

At Navigate BioPharma (BP), we develop assays for all three methods (Figure 1), partnering with leading experts to enhance detection of MRD and thereby inform treatments for AML patients. MFC is the technique of choice as it captures the widest range of patients, particularly those within the adverse risk category. Our Flow Cytometry team develops clinically meaningful MRD detection methods for multiple, late-stage clinical trials [4]. In March 2024, Zeni Alfonso, PhD, SCYM(ASCP) of Navigate BioPharma joined Prof. Jacqueline Cloos of Amsterdam UMC and Dr. Scott Bornheimer of BD Biosciences for a Wiley-hosted webinar exploring ways to leverage AML MRD in the drug development space. Our Director of Flow Cytometry, Kevin Nguyen , emphasizes the significance of this collaboration for patient outcomes: “We’re partnering with two of the most well-known and respected leaders in their areas—people at the forefront of Flow Cytometry. These partnerships enable us to get the best for our patients and customers.”

As Dr. Cloos and Dr. Alfonso both note, two key challenges to validating assays and assessing MRD are lack of sample availability and lack of scientific expertise. Securing sufficient sample amount to validate parameters like sensitivity, which requires high numbers of cells, takes time. Securing scientists with the expertise to run the tests and analyze the data can take years. Both expectations need to be factored into development planning. To hear these discussions, visit our website: www.navigatebp.com/media

Diagnostic tests (assays) developed for Flow Cytometry, qPCR, and NGS methods play a key role in cancer clinical trials as researchers evaluate patients for enrollment potential, disease progression, and treatment impact. At Navigate BP, we’ve analyzed over 2,500 patient samples for AML MRD alone. As Nguyen notes, “when we [Navigate BP] develop any test, the question at the forefront of our minds is will this assay provide the best answer for the patient with the minimal burden?” Providing more comprehensive data from less sample means the patient is going to the clinic less and having less exposure to a potentially rigorous and harmful procedure. Nguyen explains, “In practice, this takes the form of our multiplexed dPCR assay for approved CAR therapies, where we can ensure rapid enrollment of new patients regardless of which first-line CAR they were previously given. Or for something like our Flow cytometry assays--they can identify impending relapses to enable early intervention and treatment decisions.” These assays allow treatment providers to detect imminent relapses during routine checkups, which leads to earlier intervention and earlier treatment and, ultimately, to better outcomes.

Not only do we create high-complexity tests, but we also provide the data analysis that enables decision-making for the patient and clinical research organization. As noted in the webinar, this kind of expertise is essential to success. Developing the assay only meets half the need—expert scientists are required to interpret the data. We have experienced analysts and clinical data mangers to provide the interpretation and the information in formats that organizations can use to treat their patients and support their drug development programs.

At Navigate BP, our expertise allows us to go beyond running routine tests to advancing precision medicine solutions. We develop customized assays and provide data analysis to fit our partners’ needs. This combination of diagnostic development and expert interpretation makes us unique and allows us to keep patient care at the center of our daily work while turning treatment ideas into reality.

#AML #MRD #flowcytometry #patientcentric #oncology

References:

[1] https://www.cancer.org/cancer/types/acute-myeloid-leukemia/about/key-statistics.html

[2] Christopher S. Hourigan; Achieving MRD negativity in AML: how important is this and how do we get there?. Hematology Am Soc Hematol Educ Program 2022; 2022 (1): 9–14. doi: https://doi.org/10.1182/hematology.2022000323

[3] Simone E. Dekker et al., Using Measurable Residual Disease to Optimize Management of AML, ALL, and Chronic Myeloid Leukemia. Am Soc Clin Oncol Educ Book 43, e390010(2023). https://doi.org/10.1200/EDBK_390010

[4] Tettero, J. M., Dakappagari, N., Heidinga, M. E., Oussoren-Brockhoff, Y., Hanekamp, D., Pahuja, A., Burns, K., Kaur, P., Alfonso, Z., van der Velden, V. H. J., te Marvelde, J. G., Hobo, W., Slomp, J., Bachas, C., Kelder, A., Nguyen, K., & Cloos, J. (2023). Analytical assay validation for acute myeloid leukemia measurable residual disease assessment by multiparametric flow cytometry. Cytometry Part B: Clinical Cytometry, 104(6), 426–439. https://doi.org/10.1002/cyto.b.22144