Practical Application of MRD and Fixed-Duration Therapy in Clinical Practice

In this segment, Drs. Brander and Flinn explore the real-world implications of MRD monitoring and fixed-duration combination therapy for CLL, particularly in the context of the SEQUOIA trial. Dr. Flinn emphasizes that although the trial provides valuable data on the efficacy of 2- and 3-drug regimens, applying these results in clinical practice remains complex. He notes that determining which regimen is optimal for different patient populations is still challenging, as many studies use varying durations and combinations of therapy.

For high-risk patients, such as those with del(17p) or TP53 deletions, Dr. Flinn observes that longer durations of combined BTK inhibitor and venetoclax therapy may be beneficial for achieving undetectable MRD. In contrast, the approach for lower-risk patients is less clear, and ongoing follow-up will be necessary to guide treatment decisions.

In his clinical practice, MRD testing is primarily used as a post-treatment assessment rather than as a trigger to modify therapy. Peripheral blood samples are banked and tested using the ClonaSeek assay, with results helping to inform prognosis and patient counseling. Patients with MRD positivity are explained to have an intermediate prognosis, considered to be better than active disease but not the same as a complete remission, without necessarily changing therapy. Dr. Flinn notes that he rarely places high-risk del(17p) patients on fixed-duration therapy, preferring continued treatment for these individuals.

The discussion underscores the current limitations and practical challenges of using MRD to guide therapy. Although MRD offers valuable insights into depth of response, its role in modifying treatment schedules remains uncertain. Clinicians must balance trial data, patient risk factors, and clinical judgment when determining treatment duration and interpreting MRD results. This segment highlights the evolving nature of integrating MRD into routine clinical practice and emphasizes the individualized approach required for optimal patient care.