From the Guidelines
MRD testing in CLL is crucial for assessing treatment effectiveness and determining the depth of response, with MRD negativity correlating with longer progression-free survival and overall survival, as evident from the study by 1. The role of MRD testing in CLL is multifaceted, including:
- Assessing treatment effectiveness by detecting small numbers of leukemic cells that remain after therapy
- Determining the depth of response, particularly after chemoimmunotherapy or targeted therapies
- Guiding decisions about treatment duration, the need for maintenance therapy, and early intervention at molecular relapse The most common methods for MRD assessment include:
- Multiparameter flow cytometry
- Molecular techniques like PCR or next-generation sequencing, which can detect one CLL cell among 10,000 to 1,000,000 normal cells MRD negativity, typically defined as <1 CLL cell per 10,000 leukocytes, is a valuable prognostic marker, as shown in the study by 2. In clinical practice, MRD results help guide treatment decisions, and the timing of MRD assessment is typically 2-3 months after completion of therapy, with potential follow-up testing to monitor disease status over time, as recommended by 3. However, MRD testing is not yet universally recommended for routine clinical practice outside of clinical trials, though its use is increasing as evidence mounts for its prognostic value and utility in treatment decision-making, as discussed in the study by 4. The study by 5 also highlights the importance of MRD testing in CLL, particularly in the context of targeted therapies. Overall, MRD testing is a critical tool in the management of CLL, and its use is expected to become more widespread as its prognostic value and utility in treatment decision-making become more established, as evident from the studies by 1, 2, 4, 3, 5.
From the Research
Role of MRD Testing in CLL
- MRD (Minimal Residual Disease) testing is a crucial tool in the management of Chronic Lymphocytic Leukemia (CLL) 6, 7, 8, 9, 10
- MRD status has been shown to be a predictor of both progression-free survival (PFS) and overall survival (OS) at the time of response assessment following chemoimmunotherapy (CIT) 6, 7, 9, 10
- The most commonly used methods for MRD testing are flow cytometry and polymerase chain reaction (PCR), although high-throughput sequencing and more specific assays are being refined 6, 7
- MRD negativity has been associated with improved outcomes in patients receiving CIT, and emerging data suggest a relationship between MRD negativity and outcomes in patients receiving novel oral therapeutics such as venetoclax 6, 7, 8
- The prognostic value of MRD status for kinase inhibitors remains unknown, and further research is required to validate the use of MRD status as a decision point in guiding therapy in clinical practice 6, 7, 8
MRD Testing Methods
- Flow cytometry is a widely used method for MRD testing, with a sensitivity of 0.01-0.1% 6, 7, 9, 10
- PCR-based methods, such as real-time quantitative PCR (RQ-PCR) and droplet digital PCR (ddPCR), offer higher sensitivity and specificity than flow cytometry 7
- Next-generation sequencing (NGS) is a promising new technology for MRD testing, with the potential for higher sensitivity and specificity than existing methods 7, 8
Clinical Implications of MRD Testing
- MRD testing can be used to monitor response to treatment and predict outcomes in patients with CLL 6, 7, 8, 9, 10
- MRD negativity has been associated with improved outcomes, including prolonged PFS and OS, and may be a useful endpoint in clinical trials 6, 7, 8
- The use of MRD testing to guide treatment decisions, such as discontinuation of therapy, is an area of ongoing research and debate 6, 7, 8