MRD-Guided Therapy: Current and Future Practices

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MRD testing serves as an important prognostic marker in chronic lymphocytic leukemia (CLL) but should not routinely guide treatment duration or therapy change decisions according to current clinical guidelines. European and National Comprehensive Cancer Network guidelines acknowledge MRD technology and provide recommendations for appropriate testing techniques, but emphasize that MRD results inform progression-free survival expectations rather than dictate treatment modifications. In clinical practice, MRD testing has limited utility for patients receiving continuous therapy, as the majority will not achieve MRD negativity even after years of treatment.

For fixed-duration regimens like CLL14, MRD testing at treatment completion provides valuable prognostic information for patients and oncologists. Although half of patients might benefit from additional treatment cycles and half have likely received optimal benefit, treatment decisions should not be based solely on MRD status. Instead, patients should be informed that MRD detectability or conversion from negative to positive status indicates a potentially shortened time to next treatment need, while following standard progression criteria for retreatment decisions.

The role of MRD as a surrogate end point in future clinical trials remains questionable due to the lack of clear evidence that MRD negativity represents a cure for CLL. Patients can fluctuate between MRD-negative and MRD-positive status, and the kinetics of achieving MRD negativity do not necessarily correlate with long-term outcomes in all patient subsets. Given the impressive long-term data showing median progression-free survival of 8.9 years for ibrutinib, MRD negativity alone may not provide sufficient surrogate end point value for drug approval decisions or clinical practice modifications.