Treatment of Smoldering Multiple Myeloma: Ready for Prime Time?

Kim, E. Bridget; Yee, Andrew J.; Raje, Noopur

doi:10.3390/cancers12051223

Cited by 11 publications

(5 citation statements)

References 59 publications

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“…First, MM is a model of transformation from premalignant asymptomatic conditions (monoclonal gammopathy of uncertain significance -MGUS- and smouldering myeloma -smMM-) into active stages when disease-associated symptoms such as anemia, hypercalcemia, renal impairment, or bone lesions may appear. The study of this evolution has led to the clinical evaluation of the concept of early intervention for these asymptomatic patients [ 2 ]. Prognosis is another field of research in MM that started with the use of clinical parameters such as albumin or β2 microglobulin, continued with the discovery of molecular and cytogenetic abnormalities conferring adverse prognosis, and more recently, dynamic markers like the evaluation of the measurable residual disease (MRD) have been incorporated to guide treatment decisions.…”

Section: Multiple Myeloma and The Bone Marrow Microenvironmentmentioning

confidence: 99%

Bone Marrow Mesenchymal Stromal Cells in Multiple Myeloma: Their Role as Active Contributors to Myeloma Progression

Maiso

Mogollón

Ocio

et al. 2021

Cancers

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Multiple myeloma (MM) is a hematological malignancy of plasma cells that proliferate and accumulate within the bone marrow (BM). Work from many groups has made evident that the complex microenvironment of the BM plays a crucial role in myeloma progression and response to therapeutic agents. Within the cellular components of the BM, we will specifically focus on mesenchymal stromal cells (MSCs), which are known to interact with myeloma cells and the other components of the BM through cell to cell, soluble factors and, as more recently evidenced, through extracellular vesicles. Multiple structural and functional abnormalities have been found when characterizing MSCs derived from myeloma patients (MM-MSCs) and comparing them to those from healthy donors (HD-MSCs). Other studies have identified differences in genomic, mRNA, microRNA, histone modification, and DNA methylation profiles. We discuss these distinctive features shaping MM-MSCs and propose a model for the transition from HD-MSCs to MM-MSCs as a consequence of the interaction with myeloma cells. Finally, we review the contribution of MM-MSCs to several aspects of myeloma pathology, specifically to myeloma growth and survival, drug resistance, dissemination and homing, myeloma bone disease, and the induction of a pro-inflammatory and immunosuppressive microenvironment.

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Section: Multiple Myeloma and The Bone Marrow Microenvironmentmentioning

confidence: 99%

Bone Marrow Mesenchymal Stromal Cells in Multiple Myeloma: Their Role as Active Contributors to Myeloma Progression

Maiso

Mogollón

Ocio

et al. 2021

Cancers

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“…After a median follow-up of 43.3 months, 63% of patients remained MRD-negative, with estimated 4-year PFS and OS rates of 71% and 100%, respectively. A subsequent phase II study in 52 high-risk SMM patients, assessed eight cycles of KRd followed by 2 years of lenalidomide maintenance (KRd-R) [ 184 ]. After a median follow-up of 27.3 months, the ORR was 100%; only 10% of patients had developed MM after 5 years.…”

Section: Bone Marrow Modulating Agents: Clinical Applicationsmentioning

confidence: 99%

Monoclonal Gammopathies and the Bone Marrow Microenvironment: From Bench to Bedside and Then Back Again

et al. 2023

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Multiple myeloma (MM) is an incurable hematologic malignancy characterized by a multistep evolutionary pathway, with an initial phase called monoclonal gammopathy of undetermined significance (MGUS), potentially evolving into the symptomatic disease, often preceded by an intermediate phase called “smoldering” MM (sMM). From a biological point of view, genomic alterations (translocations/deletions/mutations) are already present at the MGUS phase, thus rendering their role in disease evolution questionable. On the other hand, we currently know that changes in the bone marrow microenvironment (TME) could play a key role in MM evolution through a progressive shift towards a pro-inflammatory and immunosuppressive shape, which may drive cancer progression as well as clonal plasma cells migration, proliferation, survival, and drug resistance. Along this line, the major advancement in MM patients’ survival has been achieved by the introduction of microenvironment-oriented drugs (including immunomodulatory drugs and monoclonal antibodies). In this review, we summarized the role of the different components of the TME in MM evolution from MGUS as well as potential novel therapeutic targets/opportunities.

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“…Given the long clinical course and follow-up, there is a need for reliable biomarkers, in addition to secreted monoclonal proteins, that can track disease burden and bone disease, in order to inform the timing and intensity of treatment. Such markers may additionally capture a subset of smouldering MM (SMM) patients that may benefit from earlier treatment [3,4] and refine monitoring frequency in monoclonal gammopathy of undetermined significance (MGUS) [5]. Currently, serum paraprotein and free light chains are widely used for disease monitoring; however, utility is limited in non-paraprotein-secreting MM, and although they track the secretory capacity of a plasma cell clone, that feature can change over the course of disease.…”

Section: Introductionmentioning

confidence: 99%

Prospective Assessment of Tumour Burden and Bone Disease in Plasma Cell Dyscrasias Using DW-MRI and Exploratory Bone Biomarkers

Agarwal

Nador

Varghese

et al. 2022

Cancers

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Novel biomarkers for tumour burden and bone disease are required to guide clinical management of plasma cell dyscrasias. Recently, bone turnover markers (BTMs) and Diffusion-Weighted Magnetic Resonance Imaging (DW-MRI) have been explored, although their role in the prospective assessment of multiple myeloma (MM) and monoclonal gammopathy of undetermined significance (MGUS) is unclear. Here, we conducted a pilot observational cohort feasibility study combining serum BTMs and DW-MRI in addition to standard clinical assessment. Fifty-five patients were recruited (14 MGUS, 15 smouldering MM, 14 new MM and 12 relapsed MM) and had DW-MRI and serum biomarkers (P1NP, CTX-1, ALP, DKK1, sclerostin, RANKL:OPG and BCMA) measured at baseline and 6-month follow-up. Serum sclerostin positively correlated with bone mineral density (r = 0.40−0.54). At baseline, serum BCMA correlated with serum paraprotein (r = 0.42) and serum DKK1 correlated with serum free light chains (r = 0.67); the longitudinal change in both biomarkers differed between International Myeloma Working Group (IMWG)-defined responders and non-responders. Myeloma Response Assessment and Diagnosis System (MY-RADS) scoring of serial DW-MRI correlated with conventional IMWG response criteria for measuring longitudinal changes in tumour burden. Overall, our pilot study suggests candidate radiological and serum biomarkers of tumour burden and bone loss in MM/MGUS, which warrant further exploration in larger cohorts to validate the findings and to better understand their clinical utility.

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Treatment of Smoldering Multiple Myeloma: Ready for Prime Time?

Cited by 11 publications

References 59 publications

Bone Marrow Mesenchymal Stromal Cells in Multiple Myeloma: Their Role as Active Contributors to Myeloma Progression

Bone Marrow Mesenchymal Stromal Cells in Multiple Myeloma: Their Role as Active Contributors to Myeloma Progression

Monoclonal Gammopathies and the Bone Marrow Microenvironment: From Bench to Bedside and Then Back Again

Prospective Assessment of Tumour Burden and Bone Disease in Plasma Cell Dyscrasias Using DW-MRI and Exploratory Bone Biomarkers

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