Dr Lonial on Using MRD Negativity to Guide Maintenance Discontinuation in Myeloma

Sagar Lonial, MD, of the Winship Cancer Institute of Emory University, discusses the pivotal role of measurable residual disease (MRD) monitoring in guiding lenalidomide (Revlimid) maintenance discontinuation for patients with multiple myeloma. Emerging clinical data have supported the conclusion that achieving sustained MRD negativity across consecutive annual assessments provides a safe foundation for stopping maintenance therapy. Data from the ENDURANCE trial also support discontinuation in principle, providing crucial reassurance to long-term patients who may feel apprehensive about treatment cessation, confirming that discontinuing lenalidomide after 2 years does not compromise clinical outcomes.

To effectively utilize MRD-driven discontinuation strategies, establishing an appropriate baseline is essential. Lonial emphasizes that community care teams must send an initial bone marrow sample at diagnosis for baseline tracking. A common obstacle in clinical practice occurs when community-diagnosed patients lack this initial profiling, which severely hinders the ability to monitor disease kinetics accurately over time. While both next-generation sequencing, such as the ClonoSEQ assay by Adaptive Biotechnologies, and high-sensitivity flow cytometry are valid modalities, selecting a consistent method is paramount. Next-generation sequencing offers a distinct practical advantage by archiving the baseline diagnostic sample, enabling standardized comparative analysis across different institutions regardless of where future testing takes place.

Furthermore, interpreting longitudinal MRD trends rather than relying on isolated time points dictates clinical decision-making. For example, a patient exhibiting residual or declining disease metrics between year 1 and year 2 should remain on maintenance. Conversely, a patient demonstrating zero detectable disease across 2 consecutive years represents an ideal candidate for therapy discontinuation. By conducting annual MRD evaluations and tracking longitudinal depth of response, clinicians can transition away from arbitrary treatment durations toward personalized, data-driven discontinuation protocols.