MRD Testing: Guidelines and Clinical Decision-Making in Treatment-Naive CLL

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Minimal residual disease (MRD) testing has emerged as an important tool in chronic lymphocytic leukemia (CLL) management, particularly for patients receiving fixed-duration therapy regimens. MRD testing helps clinicians determine whether patients have achieved sufficient disease clearance to safely discontinue treatment at predetermined timepoints. However, standardization remains challenging, with no universally accepted testing methodology, threshold definitions, or clinical practice guidelines for MRD interpretation and application in routine CLL care.

The lack of standardized MRD testing protocols presents significant challenges for CLL practitioners. Different assays measure varying levels of disease detection, with ongoing debates about whether MRD negativity should be defined as 10^–4 or 10^–6 response depth. Additionally, the choice between peripheral blood and bone marrow testing varies among institutions and clinical trials. Without established standards for testing frequency, methodology, or result interpretation, real-world application of MRD testing remains inconsistent across different practice settings.

Despite standardization challenges, MRD testing provides valuable information for treatment decision-making in fixed-duration CLL regimens. Patients who haven’t achieved MRD negativity at scheduled treatment completion may benefit from extended therapy duration, particularly with Bruton tyrosine kinase inhibitor components that can deepen responses over time. This personalized approach helps optimize treatment outcomes by tailoring therapy duration to individual response patterns rather than applying uniform treatment schedules to all patients.