Minimal residual disease testing in hematologic malignancies and solid cancer

Abstract

Minimal residual disease (MRD) assays are of a great value to assess treatment efficacy and may provide prognostic information. This is particularly relevant in the era of targeted therapy where the introduction of MRD monitoring has fundamentally transformed the way in which cancer patients are managed. While MRD guidelines are well-established for chronic myeloid leukemia, acute promyelocytic leukemia and acute lymphoblastic leukemia, areas for continuing development are available. High level of standardization and regular external quality control rounds and recommendations for data interpretation remain essential to improve MRD monitoring. In this review, we describe the different applications of MRD assays in most frequent hematologic malignancies and solid cancer and provide an overview of the strengths and potential weaknesses of each method.

Keywords::

• acute leukemia
• chronic myeloid leukemia
• circulating tumor cell
• CTC
• minimal residual disease
• multicolor flow cytometry
• RT-qPCR
• standardization

Financial & competing interests disclosure

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

No writing assistance was utilized in the production of this manuscript.

Key issues

• Chronic myeloid leukemia (CML) has been considered as a model disease in oncology since its discovery. CML was the first cancer associated with a chromosomal aberration, the Philadelphia chromosome. Later, CML was the first neoplasm in which the identification of the molecular abnormalities led to a rationally designed therapy: the introduction of a tyrosine kinase inhibitor as a targeted treatment has revolutionized the management of this disease.

• Developments in cancer diagnostics and minimal residual disease (MRD) assays at very early time points hold considerable promise to inform more tailored management of patients.

• MRD assays are of a great value to assess the efficacy of treatment strategies, especially if a targeted therapy exists and if alternative effective treatments are available and may change the course of the disease in case of relapse.

• Detecting circulating tumor cells from peripheral blood promises high clinical utility in monitoring therapeutic response in solid cancers; but currently, there is no consensus on the use of circulating tumor cells.

• Different MRD tests including PCR-based techniques and multicolor flow cytometry should be considered as complementary. Using them in tandem may help reduce the frequency of false-negative results and can contribute significantly to achieve better MRD informativity.

• MRD detection must be standardized to ensure comparable results between different laboratories. High level of standardization and regular external quality control rounds remain essential to improve MRD monitoring.

• Recent high throughput sequencing technologies such as next generation deep sequencing platforms lead to the identification of an increasing number of molecular aberrations recurrently observed in cancer. These technologies offer great opportunities for development of novel targeted treatments and lead to the identification of new targets for MRD detection.

Notes