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Blood Reviews Jul 2019Extramedullary disease of multiple myeloma (EM) remains a treatment challenge even in the era of new drugs. While many reports analyzing various aspects of EM have been... (Review)
Review
Extramedullary disease of multiple myeloma (EM) remains a treatment challenge even in the era of new drugs. While many reports analyzing various aspects of EM have been published, mechanism of EM development has not been clarified yet. This review summarizes current knowledge about this clinical entity, including its history, diagnostics, imaging methods, incidence, prognosis, current treatment options, risk factors and known molecular mechanisms that might be involved in pathogenesis of EM.
Topics: Humans; Multiple Myeloma
PubMed: 31005420
DOI: 10.1016/j.blre.2019.04.002 -
British Journal of Haematology Nov 2020The knowledge of disease biology as well as the therapeutic landscape in multiple myeloma (MM) has expanded exponentially in recent years. These advances have seen... (Review)
Review
The knowledge of disease biology as well as the therapeutic landscape in multiple myeloma (MM) has expanded exponentially in recent years. These advances have seen improvements in survivorship, not only in the clinical trial setting but also in the real setting. Importantly there is also every evidence to indicate that such improvements in our understanding and treatments will continue. This article is not intended to be a comprehensive review; rather it aims to give a temporal context to these developments with exemplars, and highlight the central role that UK clinicians, healthcare workers, scientists and most importantly patients and their relatives have played in this revolution.
Topics: Disease Management; Disease Susceptibility; Humans; Multiple Myeloma; Outcome Assessment, Health Care; United Kingdom
PubMed: 33190259
DOI: 10.1111/bjh.17148 -
Journal of Cellular Biochemistry Jan 2017Multiple myeloma (MM) is a malignant plasma cell disorder, clinically characterized by osteolytic lesions, immunodeficiency, and renal disease. Over the past decade, MM... (Review)
Review
Multiple myeloma (MM) is a malignant plasma cell disorder, clinically characterized by osteolytic lesions, immunodeficiency, and renal disease. Over the past decade, MM therapy is significantly improved by the introduction of novel therapeutics such as immunomodulatory agents (thalidomide, lenalidomide, and pomalidomide), proteasome inhibitors (bortezomib, carfilzomib, and ixazomib), monoclonal antibodies (daratumumab and elotuzumab), histone deacetylase (HDAC) inhibitors (Panobinostat). The clinical success of these agents has clearly identified vulnerabilities intrinsic to the MM cell, as well as targets that emanate from the tumor microenvironment. Despite these significant improvements, MM remains incurable due to the development of drug resistance. This perspective will discuss more recent strategies which take advantage of multiple targets within the proteome recycling pathway, chromatin remodeling, and disruption of nuclear export. In addition, we will review the development of strategies designed to block opportunistic survival signaling that occurs between the MM cell and the tumor microenvironment including strategies for inhibiting myeloma-induced immune suppression. It has become clear that MM tumors continue to evolve on therapy leading to drug resistance. It will be important to understand the emerging drug resistant mechanisms and additional vulnerabilities that occur due to the development of clinical resistance. J. Cell. Biochem. 118: 15-25, 2017. © 2016 Wiley Periodicals, Inc.
Topics: Animals; Antineoplastic Agents; Drug Delivery Systems; Humans; Multiple Myeloma; Neoplasm Proteins; Proteome; Signal Transduction
PubMed: 27261328
DOI: 10.1002/jcb.25617 -
Blood Cancer Journal Jul 2023While most patients diagnosed with multiple myeloma (MM) receive initial therapy, reported attrition rates are high. Understanding attrition rates and characteristics of...
While most patients diagnosed with multiple myeloma (MM) receive initial therapy, reported attrition rates are high. Understanding attrition rates and characteristics of patients not receiving subsequent therapy is useful for MM stakeholders. We performed an analysis of attrition rates in a large disease-specific database of patients with newly diagnosed MM who received at least one line of therapy between Jan 1/10-Dec 31/20. Attrition was defined as failure to receive a subsequent line of therapy despite progression of MM or due to death. A total of 5548 patients were identified, 3111 autologous stem cell transplant (ASCT) patients and 2437 non-ASCT. In the ASCT cohort, the attrition rate was 7% after line 1, 12% after line 2, and 23% after line 3. In non-ASCT patients, the attrition rate was 19% after line 1, 26% after line 2, and 40% after line 3. Death was the dominant contributor to attrition across all cohorts, with a minority of patients alive with progressive disease in the absence of further therapy at each line. Multivariable analysis identified older age, shorter time to progression, and inferior response as independent risk factors for attrition. Our data show that attrition rates increase with each line of therapy and are higher in non-ASCT patients but are appreciably lower than previously reported. This study supports a revision of the previous definition of attrition, demonstrating that most patients who do not receive subsequent therapy are either continuing their current therapy and/or are in remission off-treatment rather than being irreversibly lost to attrition.
Topics: Humans; Multiple Myeloma; Canada; Stem Cell Transplantation; Transplantation, Autologous; Hematopoietic Stem Cell Transplantation; Retrospective Studies; Antineoplastic Combined Chemotherapy Protocols
PubMed: 37474492
DOI: 10.1038/s41408-023-00883-x -
Expert Opinion on Pharmacotherapy May 2019Multiple myeloma is a disease predominately affecting older adults. Pivotal to treating older adults is understanding their physiologic differences compared to younger... (Review)
Review
INTRODUCTION
Multiple myeloma is a disease predominately affecting older adults. Pivotal to treating older adults is understanding their physiologic differences compared to younger subjects and how the complexity of therapies has an impact upon this patient population.
AREAS COVERED
Herein, the authors address the efficacy of chemotherapy regimens, decision-making for older adults, chemotherapy-associated toxicity and the approach to management. This review focuses on the complex treatment of older multiple myeloma patients and management of treatment-related adverse events.
EXPERT OPINION
Balancing efficacy and managing toxicity is a challenge for older myeloma patients. This group is more susceptible to treatment toxicities due to a higher incidence of pre-existing comorbidities and underlying diminished physiologic reserve. Intensive therapies such as autologous hematopoietic cell transplant (AHCT), however, still should be considered for all multiple myeloma patients, including older adults. The continued development of novel therapies and increased use of multi-drug regimens has changed the treatment paradigms yet understanding the complexity of the aging adult in the context of various drugs is warranted.
Topics: Antibodies, Monoclonal; Antineoplastic Agents; Hematopoietic Stem Cell Transplantation; Humans; Immunologic Factors; Multiple Myeloma; Neoplasm, Residual; Proteasome Inhibitors; Venous Thromboembolism
PubMed: 30785310
DOI: 10.1080/14656566.2019.1577822 -
Cancer Jan 2021
Topics: Bortezomib; Bridged Bicyclo Compounds, Heterocyclic; Humans; Multiple Myeloma; Prognosis
PubMed: 32966668
DOI: 10.1002/cncr.33206 -
Journal of Nuclear Medicine : Official... Jan 2016Molecular imaging plays an important role in detection and staging of hematologic malignancies. Multiple myeloma (MM) is an age-related hematologic malignancy of clonal... (Review)
Review
Molecular imaging plays an important role in detection and staging of hematologic malignancies. Multiple myeloma (MM) is an age-related hematologic malignancy of clonal bone marrow plasma cells characterized by destructive bone lesions and is fatal in most patients. Traditional skeletal survey and bone scans have sensitivity limitations for osteolytic lesions manifested in MM. Progressive biomedical imaging technologies such as low-dose CT, molecularly targeted PET, MRI, and the functional-anatomic hybrid versions (PET/CT and PET/MRI) provide incremental advancements in imaging MM. Imaging with PET and MRI using molecularly targeted probes is a promising precision medicine platform that might successfully address the clinical ambiguities of myeloma spectrum diseases. The intent of this focus article is to provide a concise review of the present status and promising developments on the horizon, such as the new molecular imaging biomarkers under investigation that can either complement or potentially supersede existing standards.
Topics: Humans; Molecular Imaging; Multiple Myeloma; Radiography; Radionuclide Imaging
PubMed: 26541780
DOI: 10.2967/jnumed.115.163808 -
The Korean Journal of Internal Medicine Sep 2016Epidemiologically, multiple myeloma (MM) is a malignant disorder of plasma cells with a higher incidence among Western populations than among Asians. However, there is... (Review)
Review
Epidemiologically, multiple myeloma (MM) is a malignant disorder of plasma cells with a higher incidence among Western populations than among Asians. However, there is growing evidence of a recent increase in the age-standardized incidence rate (ASR) of MM in Asian countries, particularly Korea. Application of novel agents has resulted in significant improvement of treatment outcomes, and the advances are ongoing with the recent introduction and U.S. Food and Drug Administration's approval of newer agents, including carfilzomib, ixazomib, elotuzumab, and daratumumab. In concert with the technical advances in the cytogenetic and molecular diagnostics of MM, modifications of its diagnosis and staging system have been attempted for better risk stratification. The modified diagnostic criteria from the International Myeloma Working Group in 2014 enabled a strategy of more active treatment for some patients with smoldering MM, with an ultra-high risk of progression, and fine-tuned the definition of end-organ damage, known as CRAB (hypercalcemia, renal insufficiency, anemia, and bone lesions). Considering Korea's trend of aging at an unprecedented rate, we can expect that the ASR of MM will maintain a gradual increase for many years to come; therefore, MM will be a cancer of critical importance from both medical and socioeconomic perspectives in Korea.
Topics: Consolidation Chemotherapy; Hematopoietic Stem Cell Transplantation; Humans; Induction Chemotherapy; Intersectoral Collaboration; Maintenance Chemotherapy; Multiple Myeloma; Neoplasm Staging; Republic of Korea
PubMed: 27604794
DOI: 10.3904/kjim.2015.408 -
Blood Cancer Journal Dec 2017
Topics: Humans; Multiple Myeloma; Neoplasm, Residual
PubMed: 29209089
DOI: 10.1038/s41408-017-0028-5 -
Hematology. American Society of... Dec 2022Smoldering multiple myeloma (SMM) is an asymptomatic precursor condition to multiple myeloma (MM). The prevalence of SMM is 0.5% in persons over 40 years old; it is...
Smoldering multiple myeloma (SMM) is an asymptomatic precursor condition to multiple myeloma (MM). The prevalence of SMM is 0.5% in persons over 40 years old; it is higher in men than women and increases with age. When SMM is diagnosed, a thorough diagnostic workup is necessary to exclude myeloma-defining events and stratify patients according to risk of progression to MM. While close monitoring for progression remains the best management for most patients with SMM, in this article, we discuss if treatment initiation before myeloma-defining events occur might be relevant in selected high-risk cases. Two randomized clinical trials have shown a clinical benefit of initiating treatment at the SMM stage, whereof 1 showed an overall survival benefit for those receiving treatment. We discuss various risk stratification models in SMM, important treatment trials, and ongoing trials. Finally, we present how to approach the clinical management of patients with SMM.
Topics: Humans; Female; Adult; Smoldering Multiple Myeloma; Risk Factors; Multiple Myeloma; Disease Progression
PubMed: 36485144
DOI: 10.1182/hematology.2022000355