Can minimal residual disease be used to tailor therapy duration for chronic lymphocytic leukemia patients?

Undetectable minimal residual disease (uMRD) has emerged as a critical prognostic and potentially predictive biomarker in chronic lymphocytic leukemia (CLL), particularly in venetoclax-based time-limited regimens.

Clinical trials such as MURANO, CLL-14, and CLL-13 have shown that uMRD at the end of treatment correlates with prolonged progression-free survival (PFS) and overall survival (OS), irrespective of disease biology. MRD-adapted strategies in BTK inhibitor + venetoclax combinations have also been explored, with studies suggesting that MRD-adapted therapy results in durable remissions and potential for reduced toxicity. Recent studies have begun to explore MRD-guided therapy duration for venetoclax + anti-CD20 monoclonal antibody regimens, allowing for tailored treatment based on the depth of response. In this review, we highlight that the predictive value of MRD appears to be regimen- and biology-specific, with differing implications for patients with mutated versus unmutated IGHV.

While fixed-duration therapy simplifies treatment, MRD-guided approaches offer a more individualized strategy that may optimize outcomes while minimizing overtreatment. Ongoing trials will further define the role of MRD-adapted therapy duration in first-line CLL treatment. Overall, MRD is a powerful tool to move beyond one-size-fits-all regimens and may become integral in personalizing CLL management across diverse therapeutic regimens.