Can I stop my treatment, doctor? Is MRD-guided therapy ready for prime time?

Indefinite maintenance therapy, typically with lenalidomide, remains a standard of care for patients with multiple myeloma, largely based on studies that demonstrated improved progression-free and overall survival compared to observation or placebo. However, these early trials often did not incorporate modern induction regimens or measurable residual disease (MRD) assessments. Despite newer induction regimens leading to high rates of MRD negativity, further intensification of maintenance remains the focus rather than de-escalation. As treatment paradigms have evolved to include quadruplet induction regimens and sensitive MRD assays, clinicians and patients increasingly question whether maintenance therapy can be safely stopped in selected individuals. This review examines the rationale for maintenance therapy, the historical data supporting its use, and emerging evidence from prospective studies suggesting that maintenance may be safely discontinued in patients with sustained multimodal MRD negativity. Patient-centered considerations, such as treatment-related toxicity, quality of life, and financial burden, underscore the importance of individualized decision-making regarding maintenance cessation. Also explored are future directions in MRD-guided treatment strategies, including de-escalation in the context of deep and sustained response. As the evidence base evolves, the challenge remains to balance the risks of indefinite therapy with the potential benefits of personalized, response-adaptive care in multiple myeloma.