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Platelets Dec 2023Multiple myeloma (MM) and its precursor states, smoldering myeloma (SM) and monoclonal gammopathy of undetermined significance (MGUS) are associated with increased...
Multiple myeloma (MM) and its precursor states, smoldering myeloma (SM) and monoclonal gammopathy of undetermined significance (MGUS) are associated with increased incidence of thrombosis, however the cause of this is unknown. Lenalidomide treatment of MM substantially improves patient survival, although significantly increases thrombotic risk by an unknown mechanism. This pilot study aimed to establish the impact of MM and its treatment with Lenalidomide on platelet function. We analyzed platelet function in MGUS, SM and MM compared to healthy controls. We report an increase in platelet reactivity in MGUS, SM, and MM where increases in fibrinogen binding, P-selectin exposure, altered receptor expression, elevated levels of aggregation and enhanced sensitivity to agonist stimulation were observed. We also demonstrate an increase in patient platelet reactivity post Lenalidomide treatment compared to pre-treatment. We show Lenalidomide treatment of platelets increased reactivity that was associated with formation of larger thrombi at arterial shear rates but not venous shear rates. This study demonstrates a clear increase in platelet reactivity and prothrombotic potential in patients with MGUS, SM and MM which is elevated further upon treatment with Lenalidomide. Our observations suggest that more detailed studies are warranted to determine mechanisms of thrombotic complications to enable the development of new preventative strategies that specifically target platelets.
Topics: Humans; Multiple Myeloma; Lenalidomide; Pilot Projects; Thrombosis; Monoclonal Gammopathy of Undetermined Significance
PubMed: 37822056
DOI: 10.1080/09537104.2023.2264940 -
Molecular Diagnosis & Therapy Jul 2024Zevorcabtagene autoleucel () is a fully humanised B cell maturation antigen (BCMA)-targeting specific chimeric antigen receptor (CAR) T-cell therapy being developed by... (Review)
Review
Zevorcabtagene autoleucel () is a fully humanised B cell maturation antigen (BCMA)-targeting specific chimeric antigen receptor (CAR) T-cell therapy being developed by CARsgen for the treatment of multiple myeloma. Zevorcabtagene autoleucel is an autologous CAR T cell comprising a fully human BCMA-specific scFv (25C2), a CD8α hinge region and transmembrane domain, a 4-1BB costimulatory domain and a CD3-ζ T cell activation domain. Zevorcabtagene autoleucel recognizes and induces selective toxicity against BCMA-expressing tumour cells leading to their elimination. In February 2024, zevorcabtagene autoleucel received its first approval in China for the treatment of adults with relapsed or refractory multiple myeloma who have progressed after ≥ 3 prior lines of therapy (including ≥ 1 proteasome inhibitor and an immunomodulatory agent). Clinical studies of zevorcabtagene autoleucel are underway in Canada and the US. This article summarizes the milestones in the development of zevorcabtagene autoleucel leading to this first approval for relapsed or refractory multiple myeloma.
Topics: Humans; Multiple Myeloma; B-Cell Maturation Antigen; Immunotherapy, Adoptive; Receptors, Chimeric Antigen; Clinical Trials as Topic; Drug Approval; Treatment Outcome
PubMed: 38888762
DOI: 10.1007/s40291-024-00723-z -
Clinical Chemistry Jan 2024Multiple myeloma (MM) is a hematological malignancy that develops over years from the asymptomatic precursors, monoclonal gammopathy of undetermined significance, and... (Review)
Review
BACKGROUND
Multiple myeloma (MM) is a hematological malignancy that develops over years from the asymptomatic precursors, monoclonal gammopathy of undetermined significance, and smoldering multiple myeloma. Recent evidence shows that by initiating treatment at an asymptomatic stage, outcomes in MM can be significantly improved. However, a vast majority of MM patients are diagnosed after the development of symptomatic end-organ damage and cannot reap the benefits of early treatment. The precursors of MM are easily detected by serum protein electrophoresis and free light chain assay of the serum, raising the question of whether population-based screening could detect MM at an asymptomatic stage and significantly expand the availability of early treatment in MM. Screening is a hallmark of care in many malignancies, and there are accepted criteria for when screening is appropriate.
CONTENT
Here we review the available relevant evidence for the introduction of screening and discuss whether screening for MM and its precursors fulfills these criteria. We also highlight gaps in our current knowledge, most notably a lack of data on the benefits and harms of screening and the lack of a defined target population. There are ongoing studies that may fill these critical gaps in the literature, but their results are still pending.
SUMMARY
Screening could lead to a paradigm shift in the care of patients with MM, but critical scientific questions need to be answered before screening of healthy individuals can be recommended. In short, we should not screen for MM and its precursors-yet.
Topics: Humans; Immunoglobulin Light Chains; Multiple Myeloma
PubMed: 38175579
DOI: 10.1093/clinchem/hvad148 -
Blood Reviews Mar 2024Multiple myeloma is a plasma cell neoplasm driven by primary (e.g. hyperdiploidy; IGH translocations) and secondary (e.g. 1q21 gains/amplifications; del(17p); MYC... (Review)
Review
Multiple myeloma is a plasma cell neoplasm driven by primary (e.g. hyperdiploidy; IGH translocations) and secondary (e.g. 1q21 gains/amplifications; del(17p); MYC translocations) chromosomal events. These are important to detect as they influence prognosis, therapeutic response and disease survival. Currently, cytogenetic testing is most commonly performed by interphase fluorescence in situ hybridisation (FISH) on aspirated bone marrow samples. A number of variations to FISH methodology are available, including prior plasma cell enrichment and incorporation of immunophenotypic plasma cell identification. Other molecular methods are increasingly being utilised to provide a genome-wide view at high resolution (e.g. single nucleotide polymorphism (SNP) microarray analysis) and these can detect abnormalities in most cases. Despite their wide application at diagnostic assessment, both FISH and SNP-array have relatively low sensitivity, limiting their use for identification of prognostically significant low-level sub-clones or for disease monitoring. Next-generation sequencing is increasingly being used to detect mutations and new FISH techniques such as by flow cytometry are in development and may address some of the current test limitations. Here we review the primary and secondary cytogenetic aberrations in myeloma and discuss the range of techniques available for their assessment.
Topics: Humans; Multiple Myeloma; Chromosome Aberrations; Translocation, Genetic; In Situ Hybridization, Fluorescence; Gene Rearrangement
PubMed: 38212176
DOI: 10.1016/j.blre.2024.101168 -
Journal of Clinical Oncology : Official... Jan 2024
Topics: Humans; Multiple Myeloma
PubMed: 37847871
DOI: 10.1200/JCO.23.02017 -
International Journal of Molecular... Mar 2024Multiple myeloma (MM) is a plasma cell disorder representing the second most common blood cancer [...].
Multiple myeloma (MM) is a plasma cell disorder representing the second most common blood cancer [...].
Topics: Humans; Multiple Myeloma; Paraproteinemias; Hematologic Neoplasms; Neoplasms, Second Primary
PubMed: 38612612
DOI: 10.3390/ijms25073799 -
Mayo Clinic Proceedings Feb 2024
Topics: Humans; Multiple Myeloma; Scleromyxedema; Paraproteinemias; Skin
PubMed: 38309938
DOI: 10.1016/j.mayocp.2023.08.022 -
Journal of Nuclear Medicine : Official... Sep 2023Recent innovative strategies have dramatically redefined the therapeutic landscape for treating multiple myeloma patients. In particular, the development and application...
Recent innovative strategies have dramatically redefined the therapeutic landscape for treating multiple myeloma patients. In particular, the development and application of immunotherapy and high-dose therapy have demonstrated high response rates and have prolonged remission duration. Over the past decade, new morphologic or hybrid imaging techniques have gradually replaced conventional skeletal surveys. PET/CT using F-FDG is a powerful imaging tool for the workup at diagnosis and for therapeutic evaluation allowing medullary and extramedullary assessment. The independent negative prognostic value for progression-free and overall survival derived from baseline PET-derived parameters such as the presence of extramedullary disease or paramedullary disease, as well as the number of focal bone lesions and SUV, has been reported in several large prospective studies. During therapeutic evaluation, F-FDG PET/CT is considered the reference imaging technique because it can be performed much earlier than MRI, which lacks specificity. Persistence of significant abnormal F-FDG uptake after therapy is an independent negative prognostic factor, and F-FDG PET/CT and medullary flow cytometry are complementary tools for detecting minimal residual disease before maintenance therapy. The definition of a PET metabolic complete response has recently been standardized and the interpretation criteria harmonized. The development of advanced PET analysis and radiomics using machine learning, as well as hybrid imaging with PET/MRI, offers new perspectives for multiple myeloma imaging. Most recently, innovative radiopharmaceuticals such as C-X-C chemokine receptor type 4-targeted small molecules and anti-CD38 radiolabeled antibodies have shown promising results for tumor phenotype imaging and as potential theranostics.
Topics: Humans; Multiple Myeloma; Fluorodeoxyglucose F18; Positron Emission Tomography Computed Tomography; Prospective Studies; Immunotherapy
PubMed: 37591548
DOI: 10.2967/jnumed.122.264972 -
The Lancet. Haematology Nov 2023
Topics: Humans; Multiple Myeloma; Disease-Free Survival; Neoplasm, Residual
PubMed: 37776871
DOI: 10.1016/S2352-3026(23)00240-5 -
European Journal of Nuclear Medicine... Jun 2024
Topics: Multiple Myeloma; Humans; Artificial Intelligence
PubMed: 38587646
DOI: 10.1007/s00259-024-06711-z