MRD in MM: Implications for clinical practice and trial design

During the Multiple Myeloma Hub Steering Committee Meeting in April 2025, key opinion leaders met to discuss the implications of measurable residual disease (MRD) on clinical practice and trial design in multiple myeloma (MM). The meeting opened with a presentation by Bruno Paiva and featured a discussion including Paul Richardson, Hang Quach, Sonja Zweegman, and Rakesh Popat. 

During their presentation, Paiva explored the evolving role of MRD in MM, highlighting both clinical and research applications. Paiva reviewed current MRD detection methods (Figure 1), evaluated sustained MRD negativity as an indicator for long-term survival outcomes (Figure 2), discussed the value of MRD as an early endpoint in clinical trials, and outlined scenarios where MRD could guide treatment decisions, such as fixed-duration therapy or reinitiation upon MRD resurgence.

Key learnings

• There are multiple assessment methods for MRD, including mass spectrometry, next-generation flow, next-generation sequencing, and positron emission tomography-computed tomography (PET-CT).

• Bone marrow remains the preferred sample type for MRD assessment in the first year of treatment due to the larger concentration of target cells leading to higher sensitivity.

• Mass spectrometry offers a minimally invasive option for ongoing monitoring after initial bone marrow-based MRD assessments.

• Sustained MRD negativity is associated with improved PFS and overall survival, making it a strong prognostic marker and a potential surrogate endpoint in clinical trials.

• MRD assessment allows for early insights into treatment efficacy, enabling comparisons between regimens before long-term outcome data such as progression-free survival (PFS) are available.

• Incorporating MRD as a clinical trial endpoint has the potential to significantly reduce required sample sizes and trial duration, therefore accelerating the evaluation and potential approval of novel therapies.

• MRD status can also inform personalized treatment strategies, including guiding treatment-discontinuation in patients with sustained MRD negativity, reducing the risk of overtreatment.

• Detecting MRD resurgence before clinical relapse could allow for earlier re-initiation of treatment.

• The prognostic relevance of MRD may differ by patient subgroup, with more research needed to clarify its role in high-risk populations and in patients with atypical disease.

• Advancing the clinical utility of MRD requires standardization of assessment, additional real-world data collection, and considered trial design to integrate MRD into the treatment of MM.