Review Highlights Use of MRD in AML, ALL, CML

A new review looks at the use of measurable residual disease (MRD) in patients with acute myeloid leukemia (AML), acute lymphocytic leukemia (ALL) and chronic myeloid leukemia (CML).

Findings were published in ASCO Educational Book.

MRD predicts disease progression and is used as an end point to monitor disease status and evaluate new treatments in leukemia, the researchers explained.

“MRD below certain thresholds is associated with longer progression-free survival (PFS) and overall survival (OS)” in these patients, they added.

There are 3 ways to perform MRD assessment: multiparameter flow-cytometry (MFC), quantitative polymerase chain reaction, or next-generation sequencing (NGS). For each leukemia type, MRD is typically measured after an initial treatment, but it can also be assessed during therapy and follow-up.

However, the authors note differences exist between MRD assessment methods. Although NGS requires many cells, is costly, and has a long turnaround time, MFC is widely available, is relatively inexpensive, and can produce results faster. However, the researchers caution there is currently no standardized MFC testing available in the United States.

Sensitivity can also vary according to the patient’s leukemia subtype. For example, “the molecular and immunological heterogeneity of AML requires tailoring the MRD assessment method(s) for specific patient populations,” the researchers wrote.

MRD plays a clinical role in AML, as studies have shown the median 5-year OS rate is 68% in MRD-negative and 34% in MRD-positive patients.

In those with AML, MRD can be carried out after 2 cycles of chemotherapy, at the end of treatment, before allogeneic hematopoietic cell transplantation (alloHCT), and during follow-up—although age and disease characteristics influence the likelihood of being MRD negative.

Because of this, the authors note it is “important to evaluate the prognostic value of MRD in the context of the current [European LeukemiaNet] risk classification, which specifies the MRD technology, time point, tissue, and cutoff for the use of MRD as a prognostic biomarker in patients with AML.”

These patients should know an appropriate MRD marker may not be available for all patients and markers may change over time. When it comes to ALL, MRD is a strong predictor of outcome and relapse risk in pediatric and adult patients, the researchers explained.

One meta-analysis found MRD was uniformly associated with event-free survival and OS in both age groups. MRD can also predict relapse in individuals with B-cell ALL (B-ALL) receiving chimeric antigen receptor T-cell therapy.

To incorporate MRD into the standard care for patients with ALL, “we recommend identification of patient-specific immunophenotypes or clonotypes for MRD tracking at baseline, then following MRD after induction, consolidation, and delayed intensification, and then every 3 to 6 months throughout the course of maintenance therapy,” the authors wrote.

These individuals should be aware of the impact MRD could have on clinical decision-making such as changes in treatment regimens and the decision to continue with alloHCT.

For patients with CML, MRD detection techniques have revealed most patients in cytogenetic response retained detectable leukemic cells, but over a wide range and varying clinical significance.

Detection of residual disease in these patients is also straightforward “as all leukemic cells carry the BCR::ABL1 fusion oncogene, the product of the t(9;22) (q34;q11) reciprocal translocation,” the researchers said.

Because MRD can influence treatment decisions in this population, the authors underscore the importance of high-quality monitoring on a regular basis.

MRD testing is not universal and more provider education is needed, along with improved access to the service. Cost, insurance approval, and proximity to tertiary care can all pose barriers to MRD testing.

Overall, “MRD has evolved to become a critical diagnostic method that predicts disease progression and is increasingly used as an important end point in evaluating novel treatments for patients with leukemia,” the authors concluded. “The science behind MRD monitoring continues to evolve, with new and more sensitive assays actively being investigated.”

Reference

Dekker SE, Rea D, Cayuela J, at al. Using measurable residual disease to optimize management of AML, ALL and chronic myeloid leukemia. Am Soc Clin Oncol Educ Book. Published online June 13, 2023. doi:10.1200/EDBK_390010