Barriers and questions for the regular use and future prospects of MRD use in MM
| 1. What is the most appropriate sensitivity threshold (10−5,10−6, or higher) to determine MRD presence? |
| 2. Should MRD− cutoffs or requirement for sustained MRD− be different according to disease risk? |
| 3. What is the optimal timing for MRD assessment? What are the optimal intervals for sustained MRD assessment? |
| 4. Can clinicians intensify or deintensify their therapeutic approaches based on MRD results at different time points? |
| 5. How can blood-based and imaging methods complement BM-based MRD assessment? |
| 6. Can MRD− be used as a surrogate marker for more clinically relevant end points (ie, PFS and ideally OS)? If yes, how “much more” MRD− is needed for a therapy to consistently lead to improve PFS/OS and in which setting (newly diagnosed vs relapsed disease, high-risk disease vs not)? |
| 7. Are there tumor-extrinsic factors that can explain early relapse in MRD– non–high-risk patients (immunome, microbiome)? |
| 8. What cells are responsible for relapse in MRD−? Are they malignant plasma cells truly present at very low thresholds, or are they phenotypically and genomically different than plasma cells? Are they amenable to sampling by BM aspiration, or are they adherent to the BM niche? |
| 1. What is the most appropriate sensitivity threshold (10−5,10−6, or higher) to determine MRD presence? |
| 2. Should MRD− cutoffs or requirement for sustained MRD− be different according to disease risk? |
| 3. What is the optimal timing for MRD assessment? What are the optimal intervals for sustained MRD assessment? |
| 4. Can clinicians intensify or deintensify their therapeutic approaches based on MRD results at different time points? |
| 5. How can blood-based and imaging methods complement BM-based MRD assessment? |
| 6. Can MRD− be used as a surrogate marker for more clinically relevant end points (ie, PFS and ideally OS)? If yes, how “much more” MRD− is needed for a therapy to consistently lead to improve PFS/OS and in which setting (newly diagnosed vs relapsed disease, high-risk disease vs not)? |
| 7. Are there tumor-extrinsic factors that can explain early relapse in MRD– non–high-risk patients (immunome, microbiome)? |
| 8. What cells are responsible for relapse in MRD−? Are they malignant plasma cells truly present at very low thresholds, or are they phenotypically and genomically different than plasma cells? Are they amenable to sampling by BM aspiration, or are they adherent to the BM niche? |