MRD-directed therapy in CLL: ready for prime time?

• Type of Material: Article
• Authors: Joanna M. Rhodes, Rutgers Cancer Institute of New Jersey; Carlos Alberto Lopez, Emory University; Jacqueline Barrientos, Columbia University
• Language: English
• Date: 2023-12-08
• Publisher: The American Society of Hematology Education Program
• Publication Version: Final Published Version
• Copyright Statement: © 2023 by The American Society of Hematology
• Final Published Version (URL): https://doi.org/10.1182/hematology.2023000441
• Title of Journal or Parent Work: Hematology
• Volume: 2023
• Issue: 1
• Start Page: 413
• End Page: 420
• Keywords: chemoimmunotherapy; chronic lymphocytic leukemia; measurable residual disease
• Research Categories: Health Sciences, Oncology; Health Sciences, Public Health; Health Sciences, Medicine and Surgery

Abstract

In recent years, the treatment paradigm for patients with chronic lymphocytic leukemia (CLL) has moved away from chemoimmunotherapy (CIT) toward the use of novel targeted agents. Commercially available drugs, including Bruton's tyrosine kinase inhibitors and the BCL2 inhibitor venetoclax, often used in combination with anti-CD20 monoclonal antibodies, are now the mainstay of therapy both in the frontline and in relapsed settings. As the landscape for CLL management evolves, therapeutic endpoints need to be redefined. Detection of measurable residual disease (MRD) is a sensitive tool to identify disease burden following treatment with several therapeutic regimens in CLL (including CIT, venetoclax-based regimens, and cellular therapies), and it has demonstrated prognostic value. Despite recent advances, the utility of MRD-directed therapy and attempts to eradicate it in routine clinical practice remain debated. There is little comparative data from clinical trials on the best assay to determine undetectable MRD (U-MRD) and whether its monitoring can lead to changes in treatment strategies. Our review discusses the definitions of MRD, assays for its detection, and its impact on long-term survival outcomes for patients with a CLL diagnosis.