MRD-driven treatment strategies in CLL: Current practice, limitations, and emerging paradigms

Area of Science:

• Hematology
• Oncology
• Clinical Trials

Background:

• Measurable residual disease (MRD) in chronic lymphocytic leukemia (CLL) has transitioned from a research tool to a key clinical trial endpoint.
• Its prognostic significance varies depending on the therapeutic class, impacting treatment individualization.

Purpose of the Study:

• To review the technical aspects of MRD assessment in CLL.
• To examine the role and interpretation of MRD across different therapeutic classes, including targeted therapies and combination strategies.
• To discuss barriers and future directions for MRD's clinical implementation.

Main Methods:

• Review of current technical platforms for MRD assessment (sensitivity, specimens).
• Analysis of MRD's prognostic and predictive value in chemoimmunotherapy, venetoclax-based, and BTK inhibitor-based regimens.
• Evaluation of MRD-guided combination trials and their outcomes.

Main Results:

• Undetectable MRD (uMRD) in time-limited venetoclax regimens predicts durable remission.
• MRD thresholds are less prognostic in continuous BTK inhibitor therapy.
• MRD-guided combination trials show feasibility, safety, and superior long-term outcomes.

Conclusions:

• MRD is evolving into a therapeutic guide, not just a prognostic marker, especially in regimens achieving deep remission.
• Tailoring treatment duration based on MRD depth and trajectory is effective and safe.
• Further research is needed to fully integrate MRD into routine CLL management.