Imaging Measurable (Minimal) Residual Disease in Multiple Myeloma

The availability of effective anti-myeloma therapies has led to the concept of new response categories that define responses deeper than conventionally defined complete response (CR). In cases of CR, deepest response, defined as minimal residual disease (MRD)-negative status, has been independently associated with prolonged progression-free survival and overall survival. In spite of an unmeasurable MRD, most patients eventually relapse. Because current methodology using flow cytometry or gene sequencing focuses on sampling MRD primarily from bone marrow, the low-level disease that may be present at other places in the skeleton and/or at extra-skeletal sites could be ultimately responsible for clinical relapse. Relevantly, sensitive imaging has the potential to complement MRD assessment by providing a complete picture of the entire bone/bone marrow compartment and extramedullary sites.

The International Myeloma Working Group (IMWG) has come up with new response categories of MRD negativity with or without the absence of disease on imaging. Multiple studies support the notion that FDG-PET has higher specificity over MRI as MRD assessment adjunct because the detection of FDG-PET-positive lesions has prognostic value in patients with multiple myeloma at diagnosis and at time of relapse. MR techniques, including functional variations, and new PET tracers add additional information for MRD evaluation.

We provide an overview discussing the shortcomings and advantages of various imaging strategies that can complement the current MRD methodology. We need more trials investigating the new PET tracers and functional MRI as MRD assessment tools. In order for sensitive imaging to be validated for MRD evaluation and response-adapted treatment algorithms, we recommend that prospective clinical trials incorporate the imaging-based definitions of newly defined IMWG response and MRD criteria.