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Haematologica Nov 2018The diagnosis of multiple myeloma can be challenging, even for experienced physicians, and requires close collaboration between numerous disciplines (orthopedics,... (Review)
Review
The diagnosis of multiple myeloma can be challenging, even for experienced physicians, and requires close collaboration between numerous disciplines (orthopedics, radiology, nuclear medicine, radiation therapy, hematology and oncology) before the final diagnosis of myeloma is made. The definition of multiple myeloma is based on the presence of clinical, biochemical, histopathological, and radiological markers of disease. Specific tests are needed both at presentation and during follow-up in order to reach the correct diagnosis and characterize the disease precisely. These tests can also serve prognostic purposes and are useful for follow-up of myeloma patients. Molecular analyses remain pivotal for defining high-risk myeloma and are used in updated patient stratifications, while minimal residual disease assessment via flow cytometry, molecular techniques and radiological approaches provides additional prognostic information on patients' long-term outcome. This pivotal information will guide our future treatment decisions in forthcoming clinical trials. The European Myeloma Network group updated their guidelines on different diagnostic recommendations, which should be of value to enable appropriate use of the recommendations both at diagnosis and during follow-up.
Topics: Multiple Myeloma; Practice Guidelines as Topic
PubMed: 30171031
DOI: 10.3324/haematol.2018.189159 -
American Journal of Hematology May 2022Major developments in the treatment of multiple myeloma (MM) over the past decade have led to a continued improvement in survival. Significant progress has been made... (Review)
Review
Major developments in the treatment of multiple myeloma (MM) over the past decade have led to a continued improvement in survival. Significant progress has been made with deeper and longer remissions seen with newer treatment approaches-both for induction as well as maintenance therapy. The treatment approach to MM is guided by several factors including patient age, frailty, comorbidities, eligibility for autologous stem cell transplantation (ASCT), and risk stratification into standard-risk or high-risk MM. High-risk MM is defined by the presence of t(4;14), t(14;16), t(14;20), del (17p), TP53 mutation, or gain (1q). Transplant eligible patients should receive 4-6 cycles of induction followed by stem cell collection. Patients can then undergo ASCT, or continue induction therapy and shift to maintenance, delaying ASCT till first relapse. Transplant ineligible patients should receive induction therapy followed by maintenance. For induction therapy prior to ASCT, a proteasome inhibitor-IMiD combination remains standard with monoclonal antibody-based quadruplets preferred in high-risk patients. Among transplant ineligible patients, those with standard-risk MM should receive DRd continued until disease progression, while bortezomib containing regimens (VRd or VRd lite) can be considered for high-risk patients. Finally, standard-risk patients should receive lenalidomide maintenance after induction/ASCT, while proteasome inhibitor-IMiD combinations should be used for high-risk patients.
Topics: Antineoplastic Combined Chemotherapy Protocols; Bortezomib; Dexamethasone; Hematopoietic Stem Cell Transplantation; Humans; Multiple Myeloma; Neoplasm Recurrence, Local; Transplantation, Autologous
PubMed: 35234302
DOI: 10.1002/ajh.26512 -
Annals of Oncology : Official Journal... Jul 2017
Topics: Follow-Up Studies; Humans; Medical Oncology; Multiple Myeloma; Neoplasm Staging; Risk Assessment
PubMed: 28453614
DOI: 10.1093/annonc/mdx096 -
Panminerva Medica Dec 2020
Topics: Antineoplastic Agents; Congresses as Topic; Humans; Immunotherapy, Adoptive; Multiple Myeloma; Stem Cell Transplantation; Treatment Outcome
PubMed: 32957745
DOI: 10.23736/S0031-0808.20.04159-2 -
British Journal of Haematology Oct 2015In November 2014 the International Myeloma Working Group (IMWG) revised the definition of multiple myeloma, such that asymptomatic patients with newly diagnosed multiple...
In November 2014 the International Myeloma Working Group (IMWG) revised the definition of multiple myeloma, such that asymptomatic patients with newly diagnosed multiple myeloma without any of the traditional 'CRAB' (hypercalcaemia, renal impairment, anaemia, bone disease) end organ damage criteria but with one of three new criteria would be recommended to start treatment. Previously, the standard of care for such patients was expectant management. These three new criteria are: greater than 60% clonal plasma cells on bone marrow biopsy, a serum free light chain (sFLC) ratio of >100 (the involved sFLC must be >100 mg/l) and greater than one unequivocal focal lesion on advanced imaging (low dose whole body computerized tomography, magnetic resonance imaging, (18) F fluorodeoxyglucose positron emission tomography). Although this would appear to affect a small number of patients, the impact of these changes are broad, leading to an increased use of advanced imaging, a debate around the management of patients previously diagnosed with smouldering myeloma, changed terminology and clinical trial design and an extension of the use of biomarkers. For the first time the philosophy of treatment in myeloma will change from treatment initiation only being triggered by overt end organ damage to an era where sub clinical risk factors will also be taken into account.
Topics: Biomarkers, Tumor; Humans; Multiple Myeloma; Radiography
PubMed: 26221971
DOI: 10.1111/bjh.13620 -
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 -
American Family Physician Mar 2017
Topics: Family Practice; Health Education; Humans; Multiple Myeloma; Patient Education as Topic
PubMed: 28318218
DOI: No ID Found -
Clinical Cancer Research : An Official... Aug 2021Among the hallmarks of cancer is the ability of neoplastic cells to evade and suppress immune surveillance to allow their growth and evolution. Nowhere is this as... (Review)
Review
Among the hallmarks of cancer is the ability of neoplastic cells to evade and suppress immune surveillance to allow their growth and evolution. Nowhere is this as apparent as in multiple myeloma, a cancer of antibody-producing plasma cells, where a complex interplay between neoplastic cells and the immune microenvironment is required for the development and progression of disease. Decades of research has led to the discovery of a number of therapeutic agents, from cytotoxic drugs to genetically engineered cells that mediate their antimyeloma effects at least partially through altering these immune interactions. In this review, we discuss the history of immunotherapy and current practices in multiple myeloma, as well as the advances that promise to one day offer a cure for this deadly disease.
Topics: Humans; Immunotherapy; Multiple Myeloma
PubMed: 33771856
DOI: 10.1158/1078-0432.CCR-20-3600 -
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 -
American Society of Clinical Oncology... Apr 2022Historically, multiple myeloma has been considered an incurable disease, mainly because of its recurrence after transient control. However, the landscape of multiple...
Historically, multiple myeloma has been considered an incurable disease, mainly because of its recurrence after transient control. However, the landscape of multiple myeloma therapeutics has significantly changed over the last 2 decades, with disease remissions lasting much longer. The advent of modern-day induction regimens, usage of high-dose melphalan followed by autologous stem cell transplantation, and well-tolerated maintenance regimens has resulted in deeper and durable responses, with less frequent disease recurrences, and patients are living much longer. Moreover, the conventional testing for response assessments in multiple myeloma was developed at least 60 years earlier, and there was a clear need for more sensitive diagnostics to test measurable residual disease at deeper levels. Next-generation sequencing and next-generation flow cytometry are highly sensitive techniques that were refined over the last decade and have a sensitivity of 10 to 10 (1 cell per 100,000/1 million). More recently, immunotherapy strategies-including the cellular therapies-have allowed us to expand our ability to achieve and maintain measurable residual disease negativity even in the refractory setting. These advances have brought us much closer to a cure for multiple myeloma; clearly, it has become more realistically achievable, challenging the dogma of multiple myeloma as an incurable disease.
Topics: Hematopoietic Stem Cell Transplantation; Humans; Multiple Myeloma; Neoplasm Recurrence, Local; Neoplasm, Residual; Transplantation, Autologous
PubMed: 35623025
DOI: 10.1200/EDBK_349603