Achieving Minimal Residual Disease (MRD) negativity is linked to longer remissions and longer survival, but it is not the end goal for every multiple myeloma patient. Some patients remain MRD-positive yet experience long, stable remissions without needing further aggressive treatment.

Why MRD Negativity Matters:

• Indicates deeper treatment response, leading to longer remissions and improved survival.
• Sustained MRD negativity over time is a strong predictor of better outcomes.

Why MRD Negativity is Not Always Necessary:

• Some MRD-positive patients still experience long disease control without immediate relapse.
• Quality of life, treatment side effects, and disease stability may be more important than reaching MRD negativity for some patients.

Factors That Influence MRD Negativity:

• Cytogenetics
  • Standard-risk patients (e.g., hyperdiploidy) are more likely to achieve MRD negativity.
  • High-risk patients (e.g., those with del(17p), t(4;14), or gain(1q21)) may have a harder time reaching or maintaining MRD negativity.
  • t(11;14) patients may benefit from targeted therapies like venetoclax to improve their chances.

• Other Key Factors
  • Depth of response – Achieving a very good partial response (VGPR) or complete response (CR) early increases the likelihood of MRD negativity.
  • Stem cell transplant (ASCT) – Patients undergoing ASCT often reach deeper responses, and they have higher odds of achieving MRD negative status.
  • Maintenance therapy – Lenalidomide maintenance improves MRD negativity rates, while high-risk patients may need a combination of medicines as maintenance therapy. 

MRD negativity is an important treatment milestone, but it should not be viewed as the only measure of success. Personalized treatment decisions based on individual response, MRD trends over time, risk factors, comorbidities, and quality of life are crucial in determining the best approach for each patient.