Abstract
The development of new resources for a more accurate diagnosis and response assessment in multiple myeloma has been a long process for decades, mainly since the middle of the 20th century. During this time, the succession of technical advances has run parallel to the better knowledge of disease biology and the availability of novel therapeutic strategies. The cornerstone of standardized criteria to uniformly evaluate the disease response in myeloma dates back to the 1990s when the key role of complete remission was established. Since then, different updates have been implemented according to available scientific evidences not always without certain controversies. The progressive improvements in survival results of myeloma patients and the growing quality of responses due to the novel therapies have led to the need of developing new tools for better monitoring of tumor burden. In this way, the concept of minimal residual disease and its key value based on the prognostic significance and the clinical relevance has been consolidated during the last years, overcoming the value of conventional response criteria or classical adverse prognosis markers. Nevertheless, its precise role in the clinical management of myeloma patients to detect early treatment failure and trigger early rescue strategies is still pending to be defined. In this review, we revisit the major milestones in the understanding of tumor reduction in multiple myeloma until the most recent imaging techniques or liquid biopsy approaches, including a critical view of conventional response criteria, whose backbone has remained unchanged during the last 20 years.
Highlights
Multiple myeloma (MM) is a plasma cell neoplasm that represents the second most frequent hematologic malignancy
Some preliminary studies have confirmed a benefit in progression-free survival (PFS) linked to the achievement of Whole-body diffusion-weighted MRI (WBDWI) negativity after autologous stem cell transplantation (ASCT) [93, 94], being a technique without ionizing radiation, which may overcome some of the limitations of PET-CT [95]
complete response (CR) in MM patients is linked with a clear improvement in survival outcomes, in the age of novel agents, but it is losing consistency in the long term
Summary
Multiple myeloma (MM) is a plasma cell neoplasm that represents the second most frequent hematologic malignancy. The IMWG criteria for response assessment from 2016 [27] prompted the new category of CR with MRD-negative status indistinctly defined by LymphoSIGHT (or any alternative validated NGS method) or by MFC according to EuroFlow standard, achieving at least a sensitivity of 10−5 This classification included a novel category of “sustained MRD-negative” for patients with MRD negativity in the marrow and by imaging confirmed minimum in 2 consecutive evaluations at 1 year apart. New techniques of mass spectrometry (MS) enable the identification of monoclonal proteins with a deeper limit of sensitivity in comparison with EP and IF [85], leading to an increased power to discriminate populations with different survival outcomes It is still pending validation in large prospective studies, but preliminary data suggest that MS may represent a less invasive alternative than MRD evaluations in bone marrow by NGS or MFC [45, 86]. Some preliminary studies have confirmed a benefit in PFS linked to the achievement of WBDWI negativity after ASCT [93, 94], being a technique without ionizing radiation, which may overcome some of the limitations of PET-CT [95]
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