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JAMA Feb 2022Multiple myeloma is a hematologic malignancy characterized by presence of abnormal clonal plasma cells in the bone marrow, with potential for uncontrolled growth causing... (Review)
Review
IMPORTANCE
Multiple myeloma is a hematologic malignancy characterized by presence of abnormal clonal plasma cells in the bone marrow, with potential for uncontrolled growth causing destructive bone lesions, kidney injury, anemia, and hypercalcemia. Multiple myeloma is diagnosed in an estimated 34 920 people in the US and in approximately 588 161 people worldwide each year.
OBSERVATIONS
Among patients with multiple myeloma, approximately 73% have anemia, 79% have osteolytic bone disease, and 19% have acute kidney injury at the time of presentation. Evaluation of patients with possible multiple myeloma includes measurement of hemoglobin, serum creatinine, serum calcium, and serum free light chain levels; serum protein electrophoresis with immunofixation; 24-hour urine protein electrophoresis; and full-body skeletal imaging with computed tomography, positron emission tomography, or magnetic resonance imaging. The Revised International Staging System combines data from the serum biomarkers β2 microglobulin, albumin, and lactate dehydrogenase in conjunction with malignant plasma cell genomic features found on fluorescence in situ hybridization-t(4;14), del(17p), and t(14;16)-to assess estimated progression-free survival and overall survival. At diagnosis, 28% of patients are classified as having Revised International Staging stage I multiple myeloma, and these patients have a median 5-year survival of 82%. Among all patients with multiple myeloma, standard first-line (induction) therapy consists of a combination of an injectable proteasome inhibitor (ie, bortezomib), an oral immunomodulatory agent (ie, lenalidomide), and dexamethasone and is associated with median progression-free survival of 41 months, compared with historical reports of 8.5 months without therapy. This induction therapy combined with autologous hematopoietic stem cell transplantation followed by maintenance lenalidomide is standard of care for eligible patients.
CONCLUSIONS AND RELEVANCE
Approximately 34 920 people in the US and 155 688 people worldwide are diagnosed with multiple myeloma each year. Induction therapy with an injectable proteasome inhibitor, an oral immunomodulatory agent and dexamethasone followed by treatment with autologous hematopoietic stem cell transplantation, and maintenance therapy with lenalidomide are among the treatments considered standard care for eligible patients.
Topics: Aged; Biomarkers; Consolidation Chemotherapy; Disease Management; Hematopoietic Stem Cell Transplantation; Humans; In Situ Hybridization, Fluorescence; Induction Chemotherapy; Maintenance Chemotherapy; Multiple Myeloma; Progression-Free Survival; Recurrence; Retreatment; Transplantation, Autologous
PubMed: 35103762
DOI: 10.1001/jama.2022.0003 -
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 -
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 -
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 -
Journal of the National Comprehensive... Jan 2022The NCCN Guidelines for Multiple Myeloma provide recommendations for diagnosis, initial workup, treatment, follow-up, and supportive care for patients with various...
The NCCN Guidelines for Multiple Myeloma provide recommendations for diagnosis, initial workup, treatment, follow-up, and supportive care for patients with various plasma cell neoplasms, including multiple myeloma. These NCCN Guidelines Insights highlight some of the important updates/changes specific to the treatment of patients with multiple myeloma in the 2022 version of the guidelines.
Topics: Humans; Multiple Myeloma
PubMed: 34991075
DOI: 10.6004/jnccn.2022.0002 -
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 -
Blood Cancer Journal Sep 2021When clonal plasma cells grow at anatomic sites distant from the bone marrow or grows contiguous from osseous lesions that break through the cortical bone, it is... (Review)
Review
When clonal plasma cells grow at anatomic sites distant from the bone marrow or grows contiguous from osseous lesions that break through the cortical bone, it is referred to as extramedullary multiple myeloma (EMD). EMD remains challenging from a therapeutic and biological perspective. The pathogenetic mechanisms are not completely understood and it is generally associated with high-risk cytogenetics which portends poor outcomes. There is a rising incidence of EMD in the era of novel agents, likely a reflection of longer OS, with no standard treatment approach. Patients benefit from aggressive chemotherapy-based approaches, but the OS and prognosis remains poor. RT has been used for palliative care. There is a need for large prospective trials for development of treatment approaches for treatment of EMD.
Topics: Animals; Bone Marrow; Chromosome Aberrations; Clone Cells; Disease Management; Humans; Multiple Myeloma; Plasma Cells
PubMed: 34588423
DOI: 10.1038/s41408-021-00527-y -
Blood Cancer Journal Mar 2022Extramedullary involvement (or extramedullary disease, EMD) represents an aggressive form of multiple myeloma (MM), characterized by the ability of a clone and/or... (Review)
Review
Extramedullary involvement (or extramedullary disease, EMD) represents an aggressive form of multiple myeloma (MM), characterized by the ability of a clone and/or subclone to thrive and grow independent of the bone marrow microenvironment. Several different definitions of EMD have been used in the published literature. We advocate that true EMD is restricted to soft-tissue plasmacytomas that arise due to hematogenous spread and have no contact with bony structures. Typical sites of EMD vary according to the phase of MM. At diagnosis, EMD is typically found in skin and soft tissues; at relapse, typical sites involved include liver, kidneys, lymph nodes, central nervous system (CNS), breast, pleura, and pericardium. The reported incidence of EMD varies considerably, and differences in diagnostic approach between studies are likely to contribute to this variability. In patients with newly diagnosed MM, the reported incidence ranges from 0.5% to 4.8%, while in relapsed/refractory MM the reported incidence is 3.4 to 14%. Available data demonstrate that the prognosis is poor, and considerably worse than for MM without soft-tissue plasmacytomas. Among patients with plasmacytomas, those with EMD have poorer outcomes than those with paraskeletal involvement. CNS involvement is rare, but prognosis is even more dismal than for EMD in other locations, particularly if there is leptomeningeal involvement. Available data on treatment outcomes for EMD are derived almost entirely from retrospective studies. Some agents and combinations have shown a degree of efficacy but, as would be expected, this is less than in MM patients with no extramedullary involvement. The paucity of prospective studies makes it difficult to justify strong recommendations for any treatment approach. Prospective data from patients with clearly defined EMD are important for the optimal evaluation of treatment outcomes.
Topics: Humans; Multiple Myeloma; Neoplasm Recurrence, Local; Plasmacytoma; Prospective Studies; Retrospective Studies; Tumor Microenvironment
PubMed: 35314675
DOI: 10.1038/s41408-022-00643-3 -
Blood Cancer Journal Mar 2023Light chain cast nephropathy (LCCN) is a leading cause of acute kidney injury (AKI) in patients with multiple myeloma (MM) and is now defined as a myeloma defining... (Review)
Review
Light chain cast nephropathy (LCCN) is a leading cause of acute kidney injury (AKI) in patients with multiple myeloma (MM) and is now defined as a myeloma defining event. While the long-term prognosis has improved with novel agents, short-term mortality remains significantly higher in patients with LCCN especially if the renal failure is not reversed. Recovery of renal function requires a rapid and significant reduction of the involved serum free light chain. Therefore, proper treatment of these patients is of the utmost importance. In this paper, we provide an algorithm for treatment of MM patients who present with biopsy-proven LCCN or in those where other causes of AKI have been ruled out. The algorithm is based on data from randomized trial whenever possible. When trial data is not available, our recommendations is based on non-randomized data and expert opinions on best practices. We recommend that all patients should enroll in a clinical trial if available prior to resorting to the treatment algorithm we outlined.
Topics: Humans; Multiple Myeloma; Acute Kidney Injury; Immunoglobulin Light Chains; Prognosis; Renal Dialysis
PubMed: 36990996
DOI: 10.1038/s41408-023-00806-w