The issue has been raised about the utilization of MRD testing in myeloma. See the section in the general community. I recapitulate my answer for the focus area as follows:
A number of issues regarding MRD.
1. It is a surrogate marker for prognosis. Negative is good, positive not good. However, it remains to be determined in on going clinical trials if
a. should therapy be changed to attempt to achieve MRD status-thus exposing patients to additional agents without disease progression
b. IF the patient achieves MRD negative, can the patient forego consolidation (e.g. transplant), maintenance therapy or tandem transplant (for high risk patients-current data supports tandem autologous transplant for high risk patients: Cavo et al Lancet Haematology 2020; Hari et al ASCO
Abstract 8506, 2020).
2. There is no uniform methodology for measuring MRD. There is one commercially approved company, Clonoseq, but many sites have their own methodology using high specificity flow or NGS. The International Myeloma Working Group has proposed EuroFlow as the universal standard but this has not been universally adopted. Thus, it is not possible to compared MRD results across studies, let alone the issue of whether it should be 10-5 or 106-the IMWG criteria CURRENTLY is 10-5. Further, MRD is NOT defined as a single measurement, the IMWG criteria require a year interval with continued MRD negativity.
3. Currently, this test can only be done on bone marrow samples. Should one subject a patient to a bone marrow for information purposes whereas, as stated above, we do not know what to do with the MRD positive or negative results at this time. It is for prognostic information only but not information that does not impact, CURRENTLY, clinical decision making. Of note, Clonoseq is trying to license a peripheral blood MRD test as the company has done recently with CLL.
At this juncture, MRD is an attractive endpoint but it is too early to truly determine the impact on clinical decision making.