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Seminars in Oncology Dec 2016Multiple myeloma (MM), although a rare disease, is the second most common hematologic malignancy. It is found in the spectrum of plasma cell dyscrasias, which begins... (Review)
Review
Multiple myeloma (MM), although a rare disease, is the second most common hematologic malignancy. It is found in the spectrum of plasma cell dyscrasias, which begins with monoclonal gammopathy of unknown significance (MGUS) to overt plasma cell leukemia and extramedullary myeloma. MM is associated with significant morbidity due to its end-organ destruction. It is a disease of the older population and its incidence in the African American population is twice that of the European American population. Improvements in the treatment of MM in the past couple of decades, beginning with the use of autologous stem cell transplantation followed by availability of novel treatments such as immunomodulatory drugs (ImIDs) and proteasome inhibitors (PIs) has transformed the natural history of the disease leading to longer survival times. Advancements in the diagnosis, monitoring, and treatment of MM are of the utmost importance as the general population lives longer due to other improvements in health care. The recent introduction of novel therapies has been paralleled by advancements in the monitoring of MM, namely, by the availability exquisitely sensitive techniques in detecting minimal residual disease. As drug development and technology continues to improve, it will be important to design rationale clinical trials enrolling patient populations that represent the overall population, including racial minorities and the elderly, so that trial results can be appropriately extrapolated. Herein, the changing epidemiology, improvements in survival, and the health disparity observed in important subgroups of MM are reviewed.
Topics: Adult; Aged; Aged, 80 and over; Humans; Middle Aged; Multiple Myeloma; Time Factors
PubMed: 28061985
DOI: 10.1053/j.seminoncol.2016.11.004 -
Cancer Treatment Reviews Nov 2021Despite significant advances in the treatment of multiple myeloma which had led to unprecedented rates of response and survival, patients still relapse, and cure remains... (Review)
Review
Despite significant advances in the treatment of multiple myeloma which had led to unprecedented rates of response and survival, patients still relapse, and cure remains elusive. We propose in this review a roadmap to achieve the dream of cure for multiple myeloma based on five complementary strategies. First, to increase knowledge about disease pathogenesis with a focus on the biology of circulating tumor cells, responsible for dissemination and extramedullary disease, and minimal residual disease clones who represent the reservoir of clonal evolution and disease recurrence. Second, to consider undetectable measurable residual disease (MRD), defined by high-sensitive techniques, as the new endpoint of therapy. Third, to treat disease causation instead of symptomatology through early detection and intervention. Thereby, by treating high-risk smoldering myeloma patients early, we may not only contribute to delay disease progression into active disease but also to increase the cure rates. Fourth, to use the most active scheme in standard-risk patients if the cure is in the horizon. Fifth, to investigate experimental therapies in newly diagnosed patients with high-risk MM, implementing early rescue intervention strategies with the goal of eradicating all tumor clones, and achieving minimal residual disease negativity.
Topics: Humans; Multiple Myeloma
PubMed: 34597912
DOI: 10.1016/j.ctrv.2021.102284 -
Blood Mar 2008Multiple myeloma is a clonal plasma cell malignancy that accounts for slightly more than 10% of all hematologic cancers. In this paper, we present a historically focused... (Review)
Review
Multiple myeloma is a clonal plasma cell malignancy that accounts for slightly more than 10% of all hematologic cancers. In this paper, we present a historically focused review of the disease, from the description of the first case in 1844 to the present. The evolution of drug therapy and stem-cell transplantation for the treatment of myeloma, as well as the development of new agents, is discussed. We also provide an update on current concepts of diagnosis and therapy, with an emphasis on how treatments have emerged from a historical perspective after certain important discoveries and the results of experimental studies.
Topics: Animals; Biomarkers, Tumor; History, 19th Century; History, 20th Century; History, 21st Century; Humans; Multiple Myeloma; Randomized Controlled Trials as Topic; Risk Factors; Stem Cell Transplantation
PubMed: 18332230
DOI: 10.1182/blood-2007-10-078022 -
Advances in Clinical and Experimental... Jan 2022Multiple myeloma (MM) is one of the most commonly diagnosed blood cancers. One criterion for the diagnosis of MM is serum and/or urine monoclonal protein produced by... (Review)
Review
Multiple myeloma (MM) is one of the most commonly diagnosed blood cancers. One criterion for the diagnosis of MM is serum and/or urine monoclonal protein produced by clonal plasmocytes. However, about 1-2% of MM cases do not have monoclonal protein. If other diagnostic criteria are present, the possibility of a diagnosis of non-secretory MM should be considered. As the different types of non-secretory MM depend on the underlying cause, the current definition is considered insufficient. Currently, both the diagnosis and treatment of non-secretory MM are the same as those of secretory MM. Due to the rarity of non-secretory MM, most findings are from retrospective studies on small groups of patients and case reports. The method of monitoring the effectiveness of MM treatment remains a problem, as it is usually based on the assessment of the percentage of clonal plasma cells in the bone marrow and imaging studies.
Topics: Bone Marrow; Humans; Multiple Myeloma; Plasma Cells; Retrospective Studies
PubMed: 34637200
DOI: 10.17219/acem/141455 -
International Journal of Hematology Jun 2022Despite substantial advances in anti-myeloma treatments, early recurrence and death remain an issue in certain subpopulations. Cytogenetic abnormalities (CAs) are the... (Review)
Review
Despite substantial advances in anti-myeloma treatments, early recurrence and death remain an issue in certain subpopulations. Cytogenetic abnormalities (CAs) are the most widely accepted predictors for poor prognosis in multiple myeloma (MM), such as t(4;14), t(14;16), t(14;20), gain/amp(1q21), del(1p), and del(17p). Co-existing high-risk CAs (HRCAs) tend to be associated with an even worse prognosis. Achievement of sustained minimal residual disease (MRD)-negativity has recently emerged as a surrogate for longer survival, regardless of cytogenetic risk. Information from newer clinical trials suggests that extended intensified treatment can help achieve MRD-negativity in patients with HRCAs, which may lead to improved outcomes. Therapy should be considered to include a 3- or 4-drug induction regimen (PI/IMiD/Dex or PI/IMiD/Dex/anti-CD38 antibody), auto-transplantation, and consolidation/maintenance with lenalidomide ± a PI. Results from ongoing clinical trials for enriched high-risk populations will reveal the precise efficacy of the investigated regimens. Genetic abnormalities of MM cells are intrinsic critical factors determining tumor characteristics, which reflect the natural course and drug sensitivity of the disease. This paper reviews the clinicopathological features of genomic abnormalities related to adverse prognosis, focusing on HRCAs that are the most relevant in clinical practice, and outline current optimal therapeutic approaches for newly diagnosed MM with HRCAs.
Topics: Chromosome Aberrations; Cytogenetic Analysis; Cytogenetics; Humans; Lenalidomide; Multiple Myeloma; Prognosis
PubMed: 35534749
DOI: 10.1007/s12185-022-03353-5 -
Hematological Oncology Jun 2019The treatment of myeloma is rapidly evolving. This article reviews the current diagnostic criteria, risk stratification, and approach to treatment of multiple myeloma.... (Review)
Review
The treatment of myeloma is rapidly evolving. This article reviews the current diagnostic criteria, risk stratification, and approach to treatment of multiple myeloma. Treatment approach for both newly diagnosed and relapsed disease are discussed.
Topics: Clinical Decision-Making; Combined Modality Therapy; Disease Management; Humans; Multiple Myeloma; Recurrence; Retreatment; Treatment Outcome
PubMed: 31187526
DOI: 10.1002/hon.2586 -
Annals of Oncology : Official Journal... Mar 2021
Topics: Follow-Up Studies; Humans; Multiple Myeloma; Societies, Medical
PubMed: 33549387
DOI: 10.1016/j.annonc.2020.11.014 -
Clinical Medicine (London, England) Jan 2019
Review
Topics: Bone Marrow; Humans; Multiple Myeloma
PubMed: 30651246
DOI: 10.7861/clinmedicine.19-1-58 -
American Society of Clinical Oncology... 2016There has been remarkable progress made in the diagnosis and treatment of multiple myeloma (MM). The median survival of the disease has doubled as a result of several... (Review)
Review
There has been remarkable progress made in the diagnosis and treatment of multiple myeloma (MM). The median survival of the disease has doubled as a result of several new active drugs. These advances have necessitated a revision of the disease definition and staging of MM. Until recently, MM was defined by the presence of end-organ damage, specifically hypercalcemia, renal failure, anemia, and bone lesions (CRAB features) that can be attributed to the clonal process. In 2014, the International Myeloma Working Group (IMWG) updated the diagnostic criteria for MM to add three specific biomarkers that can be used to diagnose the disease in patients who did not have CRAB features: clonal bone marrow plasma cells greater than or equal to 60%, serum free light chain (FLC) ratio greater than or equal to 100 provided involved FLC level is 100 mg/L or higher, or more than one focal lesion on MRI. In addition, the definition was revised to allow CT and PET-CT to diagnose MM bone disease. These changes enable early diagnosis and allow the initiation of effective therapy to prevent the development of end-organ damage for patients who are at the highest risk. A new staging system has been developed that incorporates high-risk cytogenetic abnormalities in addition to standard laboratory markers of prognosis.
Topics: Bone Marrow Cells; Humans; Magnetic Resonance Imaging; Multiple Myeloma; Neoplasm Staging; Positron Emission Tomography Computed Tomography
PubMed: 27249749
DOI: 10.1200/EDBK_159009 -
The Journal of Clinical Investigation Apr 2020Multiple myeloma (MM), a bone marrow-resident hematological malignancy of plasma cells, has remained largely incurable despite dramatic improvements in patient outcomes... (Review)
Review
Multiple myeloma (MM), a bone marrow-resident hematological malignancy of plasma cells, has remained largely incurable despite dramatic improvements in patient outcomes in the era of myeloma-targeted and immunomodulatory agents. It has recently become clear that T cells from MM patients are able to recognize and eliminate myeloma, although this is subverted in the majority of patients who eventually succumb to progressive disease. T cell exhaustion and a suppressive bone marrow microenvironment have been implicated in disease progression, and once these are established, immunotherapy appears largely ineffective. Autologous stem cell transplantation (ASCT) is a standard of care in eligible patients and results in immune effects beyond cytoreduction, including lymphodepletion, T cell priming via immunogenic cell death, and inflammation; all occur within the context of a disrupted bone marrow microenvironment. Recent studies suggest that ASCT reestablishes immune equilibrium and thus represents a logical platform in which to intervene to prevent immune escape. New immunotherapies based on checkpoint inhibition targeting the immune receptor TIGIT and the deletion of suppressive myeloid populations appear attractive, particularly after ASCT. Finally, the immunologically favorable environment created after ASCT may also represent an opportunity for approaches utilizing bispecific antibodies or chimeric antigen receptor T cells.
Topics: Hematopoietic Stem Cell Transplantation; Humans; Immunotherapy; Multiple Myeloma; Transplantation, Autologous; Tumor Microenvironment
PubMed: 32149732
DOI: 10.1172/JCI129205