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International Journal of Molecular... Nov 2021Multiple myeloma (MM) is a genetically complex disease that results from a multistep transformation of normal to malignant plasma cells in the bone marrow. However, the... (Review)
Review
Multiple myeloma (MM) is a genetically complex disease that results from a multistep transformation of normal to malignant plasma cells in the bone marrow. However, the molecular mechanisms responsible for the initiation and heterogeneous evolution of MM remain largely unknown. A fundamental step needed to understand the oncogenesis of MM and its response to therapy is the identification of driver mutations. The introduction of gene expression profiling (GEP) in MM is an important step in elucidating the molecular heterogeneity of MM and its clinical relevance. Since some mutations in myeloma occur in non-coding regions, studies based on the analysis of mRNA provide more comprehensive information on the oncogenic pathways and mechanisms relevant to MM biology. In this review, we discuss the role of gene expression profiling in understanding the biology of multiple myeloma together with the clinical manifestation of the disease, as well as its impact on treatment decisions and future directions.
Topics: Biomarkers, Tumor; Gene Expression Regulation, Neoplastic; Humans; Molecular Targeted Therapy; Multiple Myeloma; RNA, Messenger
PubMed: 34769503
DOI: 10.3390/ijms222112070 -
Haematologica Jun 2020
Topics: Humans; Multiple Myeloma; Phosphatidylinositol 3-Kinases
PubMed: 32482753
DOI: 10.3324/haematol.2020.248971 -
British Journal of Haematology May 2019
Topics: Chromosome Aberrations; Chromosomes, Human; Cytogenetic Analysis; Humans; Multiple Myeloma
PubMed: 30706441
DOI: 10.1111/bjh.15781 -
Hematology. American Society of... Dec 2017In recent years, several new drugs have been approved for the treatment of multiple myeloma. Many of these newer drugs are highly efficacious and less toxic than older... (Review)
Review
In recent years, several new drugs have been approved for the treatment of multiple myeloma. Many of these newer drugs are highly efficacious and less toxic than older chemotherapy drugs. In 2014, the diagnostic criteria for multiple myeloma were revised. The intent with the new criteria was to identify patients who require therapy at an earlier stage than at manifestation of organ complications. A subset of patients who were previously defined as having high-risk smoldering multiple myeloma was redefined as having multiple myeloma. In this context, it is logical to raise questions regarding the optimal clinical management of patients who are diagnosed with smoldering multiple myeloma in the current era. When is the optimal time to start therapy? Do the clinical trajectories for patients suggest there are distinct sub-entities hidden in the current category of smoldering multiple myeloma? How can we move the field forward from here? This paper reviews and dissects data and models on the topics of clinical features, underlying biology, and early treatment trials in smoldering multiple myeloma. The text highlights assumptions, facts, and gaps in the literature. As indicated in the title of the paper, the recurrent theme of the text is this: shall we treat smoldering multiple myeloma in the near future?
Topics: Humans; Multiple Myeloma; Time Factors
PubMed: 29222256
DOI: 10.1182/asheducation-2017.1.194 -
Blood Cancer Journal Nov 2023
Topics: Humans; Aged; Multiple Myeloma
PubMed: 37938551
DOI: 10.1038/s41408-023-00939-y -
Annals of Hematology Jan 2019Multiple myeloma is one of the most common hematological malignancies, affecting mainly elderly patients. The treatment landscape for the management of this disease has... (Review)
Review
Multiple myeloma is one of the most common hematological malignancies, affecting mainly elderly patients. The treatment landscape for the management of this disease has evolved significantly over the past 15 years, and a vast array of therapeutics is now available, including immunomodulatory drugs, proteasome inhibitors, histone deacetylase inhibitors, and monoclonal antibodies. As a result, deciding which drugs to use and when, and whether these should be used in a particular order or combination, can be challenging. Although combination regimens are often associated with deeper responses and better long-term outcomes than monotherapy, and are becoming the standard of care, they may result in significant incremental toxicity; hence, a sequential approach may be more appropriate for some patients. In particular, treatment choices can vary depending on whether the patient has newly diagnosed multiple myeloma, is eligible for transplant, has relapsed and/or refractory multiple myeloma, or is considered to have high-risk disease. In this review, we discuss factors to be taken into account when making treatment decisions in each of these settings. We also briefly discuss possible therapeutic strategies involving agents that may become available in the future.
Topics: Antineoplastic Agents, Immunological; Antineoplastic Combined Chemotherapy Protocols; Histone Deacetylase Inhibitors; Humans; Immunologic Factors; Multiple Myeloma; Proteasome Inhibitors
PubMed: 30470875
DOI: 10.1007/s00277-018-3546-8 -
Blood Cancer Journal Dec 2023There are significant disparities with regards to incidence, timely diagnosis, access to treatment, clinical trial participation and health care utilization that... (Review)
Review
There are significant disparities with regards to incidence, timely diagnosis, access to treatment, clinical trial participation and health care utilization that negatively impact outcomes for African American patients with multiple myeloma. Health care providers have a role in ameliorating these disparities with thoughtful consideration of historical, sociocultural, individual and disease characteristics that influence the care provided to African American patient population. This review by a group of experts committed to health disparity in multiple myeloma provides a snapshot of disparities at both biologic and non-biologic levels, barriers to clinical care, and best practices to ensure that African American patients receive the best care available.
Topics: Humans; Black or African American; Delivery of Health Care; Multiple Myeloma; Patient Acceptance of Health Care; Healthcare Disparities
PubMed: 38110338
DOI: 10.1038/s41408-023-00961-0 -
Cancer Aug 2019High-dose chemotherapy and autologous stem cell transplantation (ASCT) are a standard of care for transplant-eligible patients with newly diagnosed multiple myeloma... (Review)
Review
High-dose chemotherapy and autologous stem cell transplantation (ASCT) are a standard of care for transplant-eligible patients with newly diagnosed multiple myeloma (MM). The introduction of novel agents, which range from immunomodulatory drugs and proteasome inhibitors to monoclonal antibodies and have now been integrated into both induction and salvage regimens, has dramatically revolutionized the treatment landscape of MM and challenged the role of high-dose chemotherapy and ASCT in treating MM. These advances have led to a number of provocative questions. First, what is the current role of stem cell transplantation (SCT) in comparison with standard-dose therapy incorporating novel agents? Second, should ASCT be performed upfront ("early") or later ("delayed") in the course of the disease? Third, should single or double ASCT be performed? Fourth, is allogeneic SCT still an option for patients with MM? This article provides an overview of available data and evidence-based responses regarding the role of SCT in MM.
Topics: Hematopoietic Stem Cell Transplantation; Humans; Multiple Myeloma; Retrospective Studies; Transplantation Conditioning
PubMed: 30985927
DOI: 10.1002/cncr.32060 -
Frontiers in Immunology 2023Subsets of patients diagnosed with a monoclonal gammopathy of undetermined significance (MGUS), smoldering multiple myeloma (SMM) or multiple myeloma (MM), present with... (Review)
Review
Determination of the target of monoclonal immunoglobulins: a novel diagnostic tool for individualized MGUS therapy, and prevention and therapy of smoldering and multiple myeloma.
Subsets of patients diagnosed with a monoclonal gammopathy of undetermined significance (MGUS), smoldering multiple myeloma (SMM) or multiple myeloma (MM), present with a monoclonal immunoglobulin (Ig) specific for an infectious pathogen, including hepatitis C and B viruses (HCV, HBV), and several . Such cases are likely initiated by infection, since in the context of HCV- or HBV-infected patients, antiviral therapy can lead to the disappearance of antigenic stimulation, control of clonal plasma cells, and reduced or suppressed monoclonal Ig production. Complete remission has been obtained with anti-HCV therapy in refractory MM with a HCV-specific monoclonal Ig, and antiviral treatments significantly improved the probability of survival of MM patients infected with HCV or HBV prior to the diagnosis of MM. Monoclonal Igs may also target glucolipids, particularly glucosylsphingosine (GlcSph), and GlcSph-reducing therapy can lead to complete remission in SMM and MM patients presenting with a GlcSph-specific monoclonal Ig. The present review describes the importance of determining the target of the monoclonal Ig of MGUS, SMM and MM patients, and discusses the efficacy of target-reducing treatments in the management of MGUS, SMM and MM cases who present with a monoclonal Ig reactive against a treatable infectious pathogen or GlcSph.
Topics: Humans; Multiple Myeloma; Monoclonal Gammopathy of Undetermined Significance; Smoldering Multiple Myeloma; Paraproteins; Antibodies, Monoclonal; Hepatitis C
PubMed: 38022528
DOI: 10.3389/fimmu.2023.1253363 -
Cancer Treatment and Research... 2021Supportive care in multiple myeloma (MM) can have a major impact on quality of life and the survival outcomes of MM patients. In this review, we will focus on disease...
Supportive care in multiple myeloma (MM) can have a major impact on quality of life and the survival outcomes of MM patients. In this review, we will focus on disease and treatment related toxicities experienced by MM patients and what are the best approaches to date to help mitigate the effects. We will specifically focus on a practical approach to managing bone disease, thrombosis, infection risk, peripheral neuropathy, dermatologic complications, gastrointestinal and ocular toxicities, and fatigue in MM.
Topics: Humans; Multiple Myeloma; Palliative Care; Quality of Life
PubMed: 34653748
DOI: 10.1016/j.ctarc.2021.100476