Abstract
The treatment approach for multiple myeloma (MM) has changed in recent years. After the approval of maintenance treatment after stem cell transplant in younger patients, the paradigm of continuous treatment is now prevailing in all clinical situations of myeloma. However, the best time to initiate relapse treatment is still unclear. With increased frequency of minimal residual disease (MRD) negativity, and the established clinical benefit of this finding, one of the large clinical questions in myeloma is how to approach MRD re-appearance. In this paper, we go through the MRD technology, existing and possible uses of MRD in the clinic, and data for early treatment before we introduce the design of the ongoing REMNANT study; a randomized study with early treatment of MRD relapse after first line treatment.
Highlights
Myeloma is a neoplastic expansion of bone marrow (BM) plasma cells, and typical clinical features are anemia, renal failure, and breakdown of skeletal bone with accompanying pathological fractures and bone pain
The analysis revealed a clear association between minimal residual disease (MRD) negativity and improved progression free survival (PFS) and supports the use of MRD negativity as a surrogate endpoint in clinical trials
A robust association between depth of response measured by MRD and PFS has been demonstrated in several randomized trials in newly diagnosed myeloma patients (NDMM) and RRMM and should support the use of MRD assessment as a surrogate endpoint for all future trials in MM
Summary
Myeloma is a neoplastic expansion of bone marrow (BM) plasma cells, and typical clinical features are anemia, renal failure, and breakdown of skeletal bone with accompanying pathological fractures and bone pain. In 2014, new sub-clinical myeloma-defining biomarkers were included in the definition of MM, which provide earlier treatment for many patients and have been introduced in some centers. Changes in treatment paradigm may have the potential to significantly limit disease-related complications such as fractures and kidney failure and improve QoL for patients with MM. Achievement of both sustained complete response (CR) and stringent CR was the treatment goal and was associated with improved progression free survival (PFS) and OS. Most patients in >CR eventually relapsed, indicating that resistant sub-clones were present, even after intensified therapy. This demonstrates the need for more sensitive methods to monitor minimal residual disease (MRD), and new technologies have provided the way to analyze this
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