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JAMA Oncology Sep 2018Multiple myeloma (MM) is a plasma cell neoplasm with substantial morbidity and mortality. A comprehensive description of the global burden of MM is needed to help direct...
INTRODUCTION
Multiple myeloma (MM) is a plasma cell neoplasm with substantial morbidity and mortality. A comprehensive description of the global burden of MM is needed to help direct health policy, resource allocation, research, and patient care.
OBJECTIVE
To describe the burden of MM and the availability of effective therapies for 21 world regions and 195 countries and territories from 1990 to 2016.
DESIGN AND SETTING
We report incidence, mortality, and disability-adjusted life-year (DALY) estimates from the Global Burden of Disease 2016 study. Data sources include vital registration system, cancer registry, drug availability, and survey data for stem cell transplant rates. We analyzed the contribution of aging, population growth, and changes in incidence rates to the overall change in incident cases from 1990 to 2016 globally, by sociodemographic index (SDI) and by region. We collected data on approval of lenalidomide and bortezomib worldwide.
MAIN OUTCOMES AND MEASURES
Multiple myeloma mortality; incidence; years lived with disabilities; years of life lost; and DALYs by age, sex, country, and year.
RESULTS
Worldwide in 2016 there were 138 509 (95% uncertainty interval [UI], 121 000-155 480) incident cases of MM with an age-standardized incidence rate (ASIR) of 2.1 per 100 000 persons (95% UI, 1.8-2.3). Incident cases from 1990 to 2016 increased by 126% globally and by 106% to 192% for all SDI quintiles. The 3 world regions with the highest ASIR of MM were Australasia, North America, and Western Europe. Multiple myeloma caused 2.1 million (95% UI, 1.9-2.3 million) DALYs globally in 2016. Stem cell transplantation is routinely available in higher-income countries but is lacking in sub-Saharan Africa and parts of the Middle East. In 2016, lenalidomide and bortezomib had been approved in 73 and 103 countries, respectively.
CONCLUSIONS AND RELEVANCE
Incidence of MM is highly variable among countries but has increased uniformly since 1990, with the largest increase in middle and low-middle SDI countries. Access to effective care is very limited in many countries of low socioeconomic development, particularly in sub-Saharan Africa. Global health policy priorities for MM are to improve diagnostic and treatment capacity in low and middle income countries and to ensure affordability of effective medications for every patient. Research priorities are to elucidate underlying etiological factors explaining the heterogeneity in myeloma incidence.
Topics: Adolescent; Adult; Aged; Aged, 80 and over; Antineoplastic Agents; Bortezomib; Cause of Death; Female; Geography; Global Burden of Disease; Global Health; Humans; Incidence; Lenalidomide; Male; Middle Aged; Multiple Myeloma; Quality-Adjusted Life Years; Young Adult
PubMed: 29800065
DOI: 10.1001/jamaoncol.2018.2128 -
Transplantation and Cellular Therapy Jan 2024Since 2021, 2 B cell maturation antigen (BCMA)-directed chimeric antigen receptor T cell (CAR-T) therapies-idecabtagene vicleucel (ide-cel), and ciltacabtagene... (Review)
Review
Chimeric Antigen Receptor T Cell Therapy for Myeloma: Where Are We Now and What Is Needed to Move Chimeric Antigen Receptor T Cells Forward to Earlier Lines of Therapy? Expert Panel Opinion from the American Society for Transplantation and Cellular Therapy.
Since 2021, 2 B cell maturation antigen (BCMA)-directed chimeric antigen receptor T cell (CAR-T) therapies-idecabtagene vicleucel (ide-cel), and ciltacabtagene autoleucel (cilta-cel)-have been approved by the US Food and Drug Administration (FDA) for treating relapsed or refractory multiple myeloma (RRMM) after 4 or more prior lines of therapy, including an immunomodulatory drug, a proteasome inhibitor, and an anti-CD38 antibody. The 2 products have shown unprecedented activity in RRMM, but relapses remain common, and access to and safety of CAR-T therapy in patients with rapidly progressing advanced disease are not ideal. Sequencing CAR-T therapy with other options, including the 2 recently approved BCMA-directed T cell-engaging bispecific antibodies teclistamab and elranatamab, has become increasingly challenging owing to data showing inferior outcomes from CAR-T therapy after prior BCMA-directed therapy. This has led to the consideration of CAR-T therapy earlier in the course of disease for myeloma, when T cells are potentially healthier and the myeloma is less aggressive. To address the question of earlier use of CAR-T therapy, several trials are either ongoing or planned, and results have recently been reported for 2 randomized trials of CAR-T therapy showing improved progression-free survival compared to standard of care therapy in second-line (CARTITUDE-4) or third-line therapy (KarMMA-3). With the anticipation of the FDA possibly expanding approval of CAR-T to earlier lines of myeloma therapy, the American Society for Transplantation and Cellular Therapy convened a group of experts to provide a comprehensive review of the studies that led to the approval of CAR-T therapy in late-line therapy for myeloma, discuss the recently reported and ongoing studies designed to move CAR-T therapy to earlier lines of therapy, and share insights and considerations for sequencing therapy and optimization of patient selection for BCMA-directed therapies in current practice.
Topics: Humans; Multiple Myeloma; Receptors, Chimeric Antigen; B-Cell Maturation Antigen; Neoplasm Recurrence, Local; Neoplasms, Plasma Cell; Cell- and Tissue-Based Therapy; Antibodies, Bispecific
PubMed: 37913909
DOI: 10.1016/j.jtct.2023.10.022 -
Revista Medica de Chile Aug 2019Hematological neoplasms are tumors of cells in different states of maturation and differentiation. Since monoclonal gammopathies (MG) refer to B mature lymphocyte... (Review)
Review
Hematological neoplasms are tumors of cells in different states of maturation and differentiation. Since monoclonal gammopathies (MG) refer to B mature lymphocyte neoplasms, lymphogenesis should be well known. We must keep in mind that the last stage of maturation of these lymphocytes is the plasma cell. This is how a MG could appear in the context of a plasma cell neoplasm, such as multiple myeloma or amyloidosis, but also in relation to a lymphoma. A monoclonal peak is produced by mature B lymphocytes or plasma cells that secrete a monoclonal protein (Immunoglobulin), and represents a MG. But it must be emphasized that, in the correct clinical context, a hypogammaglobulinemia can represent a MG as well. Another important point is the understanding and interpretation of requested tests, such as protein electrophoresis (PEP), immunofixation (IFx) or serum free light chains (sFLC). The current MG screening panel includes these three studies (PEF, IFx, sFLC), although a simpler panel measuring PEF and sFLC has also been proposed, but not yet formally validated. Therefore, screening done only with PEP is insufficient.
Topics: B-Lymphocytes; Blood Protein Electrophoresis; Humans; Neoplasms, Plasma Cell; Paraproteinemias; Paraproteins
PubMed: 31859969
DOI: 10.4067/S0034-98872019000801036 -
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 -
Blood Reviews May 2011Plasma cell leukemia (PCL) is a rare, yet aggressive plasma cell (PC) neoplasm, variant of multiple myeloma (MM), characterized by high levels of PCs circulating in the... (Review)
Review
Plasma cell leukemia (PCL) is a rare, yet aggressive plasma cell (PC) neoplasm, variant of multiple myeloma (MM), characterized by high levels of PCs circulating in the peripheral blood. PCL can either originate de novo (primary PCL) or as a secondary leukemic transformation of MM (secondary PCL). Presenting signs and symptoms are similar to those seen in MM such as renal insufficiency, hypercalcemia, lytic bone lesions, anemia, and thrombocytopenia, but can also include hepatomegaly and splenomegaly. The diagnostic evaluation of a patient with suspected PCL should include a review of the peripheral blood smear, bone marrow aspiration and biopsy, serum protein electrophoresis (SPEP) with immunofixation, and protein electrophoresis of an aliquot from a 24h urine collection (UPEP). The diagnosis is made when a monoclonal population of PCs is present in the peripheral blood with an absolute PC count exceeding 2000/μL and PC comprising 20% or more of the peripheral blood white cells. The prognosis of PCL is poor with a median survival of 7 to 11 months. Survival is even shorter (2 to 7 months) when PCL occurs in the context of refractory or relapsing MM. There have been no prospective randomized trials investigating the treatment of PCL. Recommendations are primarily based upon data from small retrospective series, case reports, and extrapolation of data from patients with MM. In general, patients are treated with induction therapy followed by hematopoietic cell transplantation (HCT) in those who are appropriate candidates for this approach. The best induction regimen for PCL is not known and there is great variability in clinical practice. Newer agents that are being incorporated into frontline and salvage therapy for MM have also demonstrated activity in PCL such as Immunomodulatory agents and the use of bortezomib with different combinations.
Topics: Aged; Humans; Immunophenotyping; Leukemia, Plasma Cell; Male; Multiple Myeloma; Survival Analysis
PubMed: 21295388
DOI: 10.1016/j.blre.2011.01.005 -
The Neuroradiology Journal Jun 2017Radiology provides a crucial clinical adjunct in patients with plasma cell disorders, in particular multiple myeloma, and its uses are evolving and expanding. This... (Review)
Review
Radiology provides a crucial clinical adjunct in patients with plasma cell disorders, in particular multiple myeloma, and its uses are evolving and expanding. This pictorial review illustrates the role of imaging throughout the patient's clinical course, with specific reference to recently updated international diagnostic criteria. At presentation, imaging optimises characterisation and staging of the plasma-cell disorder, while later in the course of the disease, its roles include the monitoring of disease progression, assessment of post-treatment response and the investigation of clinical deterioration.
Topics: Disease Progression; Humans; Multiple Myeloma; Spinal Neoplasms
PubMed: 28423980
DOI: 10.1177/1971400917699426 -
Annals of Hematology Apr 2022With the advent of novel, highly effective therapies for multiple myeloma (MM), classical serologic monitoring appears insufficient for response assessment and...
With the advent of novel, highly effective therapies for multiple myeloma (MM), classical serologic monitoring appears insufficient for response assessment and prediction of relapse. Moreover, serologic studies in MM are hampered by interference of therapeutic antibodies. The detection of malignant plasma cell clones by next generation sequencing (NGS) or multiparameter flow cytometry (MFC) circumvents these difficulties and can be performed in the peripheral blood (pB) by targeting circulating cell-free DNA (cfDNA) or circulating plasma cells (CPCs), thus also avoiding an invasive sampling procedure. Here, we applied NGS of VJ light chain (LC) rearrangements in cfDNA and MFC of magnetically-enriched CD138-positive CPCs (me-MFC) to investigate disease burden in unselected MM patients. Sequencing was successful for 114/130 (87.7%) cfDNA samples and me-MFC results were analyzable for 196/205 (95.6%) samples. MM clones were detectable in 38.9% of samples taken at initial diagnosis or relapse (ID/RD), but only in 11.8% of samples taken during complete remission (CR). Circulating MM plasma cells were present in 83.3% of ID/RD samples and 9.9% of CR samples. Residual disease assessment by NGS or me-MFC in samples taken during very good partial remission or CR was 80% concordant. Notably, 4/4 (NGS) and 5/8 (me-MFC) positive CR samples were from patients with oligo- or non-secretory myeloma. The time to progression was shorter if there was evidence of residual myeloma in the pB. Together, our findings indicate that our two novel analytical approaches accurately indicate the course of MM and may be particularly valuable for monitoring patients with serologically non-trackable disease.
Topics: Cell-Free Nucleic Acids; Flow Cytometry; Humans; Multiple Myeloma; Neoplasm Recurrence, Local; Neoplasm, Residual; Plasma Cells
PubMed: 35106639
DOI: 10.1007/s00277-022-04771-5 -
International Journal of Molecular... Jan 2019Bone marrow angiogenesis plays an important role in the pathogenesis and progression of hematological malignancies. It is well known that tumor microenvironment promotes... (Review)
Review
Bone marrow angiogenesis plays an important role in the pathogenesis and progression of hematological malignancies. It is well known that tumor microenvironment promotes tumor angiogenesis, proliferation, invasion, and metastasis, and also mediates mechanisms of therapeutic resistance. An increased number of mast cells has been demonstrated in angiogenesis associated with hematological tumors. In this review we focused on the role of mast cells in angiogenesis in human plasma cell malignancies. In this context, mast cells might act as a new target for the adjuvant treatment of these tumors through the selective inhibition of angiogenesis, tissue remodeling and tumor-promoting molecules, permitting the secretion of cytotoxic cytokines and preventing mast cell-mediated immune suppression.
Topics: Animals; Biomarkers; Bone Marrow; Cell Count; Cell Transformation, Neoplastic; Disease Susceptibility; Humans; Mast Cells; Multiple Myeloma; Neoplasms, Plasma Cell; Neovascularization, Pathologic; Plasmacytoma; Tumor Microenvironment
PubMed: 30678047
DOI: 10.3390/ijms20030481 -
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 -
American Journal of Transplantation :... May 2018Plasma cell diseases are a class of hematologic diseases that are sometimes present as preexisting diagnoses prior to organ transplantation, causative factors leading to... (Review)
Review
Plasma cell diseases are a class of hematologic diseases that are sometimes present as preexisting diagnoses prior to organ transplantation, causative factors leading to a need for organ transplantation, or may occur posttransplant as part of the spectrum of posttransplant lymphoproliferative disorders. Herein, we review the most common plasma cell diseases, both as coexisting with other causes of organ failure, but also as a primary underlying cause for organ failure. In many cases, treatment of the underlying clonal disease may be indicated before proceeding with organ transplant. This review aims to provide current and relevant data regarding the management of these conditions in the organ transplant patient, for transplant providers, and those who take care of these patients.
Topics: Graft Rejection; Humans; Multiple Myeloma; Neoplasms, Plasma Cell; Organ Transplantation; Plasma Cells; Risk Factors
PubMed: 29524307
DOI: 10.1111/ajt.14731