Assessment of Minimal Residual Disease (MRD) in Chronic Lymphocytic Leukemia: A Review of the Data and Future Directions

摘要

Until recently, MRD had been relegated to the role of a prognostic factor in patients with CLL. However, in both the United States and Europe, there is tremendous interest in using MRD for other purposes. The first is as a potential surrogate endpoint in the context of clinical trials, in order to allow those trials to provide results earlier. That surrogate endpoint would potentially be for PFS, which is a standard endpoint used in key clinical trials in CLL at this time. The second is use of MRD as a measure of depth of response to guide clinical decision-making. At this time, neither of these uses are clinically accepted practices. Instead, most clinical trials in CLL use MRD status as a secondary or exploratory endpoint. Most of the clinical trials that have explored chemotherapy and/or novel agents have utilized methods such as flow cytometry, ASO-PCR, or next-generation sequencing (NGS) for measuring MRD, but only in the context of a prognostic factor. Although it is tempting to alter patient management based on persistent MRD, or even to shorten therapy based on uMRD in the peripheral blood or the bone marrow, there are no validated clinical trial data to fully support these practices today.