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American Journal of Hematology Aug 2022Multiple myeloma accounts for approximately 10% of hematologic malignancies.
DISEASE OVERVIEW
Multiple myeloma accounts for approximately 10% of hematologic malignancies.
DIAGNOSIS
The diagnosis requires ≥10% clonal bone marrow plasma cells or a biopsy-proven plasmacytoma plus evidence of one or more multiple myeloma defining events (MDE): CRAB (hypercalcemia, renal failure, anemia, or lytic bone lesions) attributable to the plasma cell disorder, bone marrow clonal plasmacytosis ≥60%, serum involved/uninvolved free light chain (FLC) ratio ≥ 100 (provided involved FLC is ≥100 mg/L), or >1 focal lesion on magnetic resonance imaging.
RISK STRATIFICATION
The presence of del(17p), t(4;14), t(14;16), t(14;20), gain 1q, or p53 mutation is considered high-risk multiple myeloma. The presence of any two high risk factors is considered double-hit myeloma, and three or more high risk factors is triple-hit myeloma.
RISK-ADAPTED INITIAL THERAPY
In patients who are candidates for autologous stem cell transplantation, induction therapy consists of bortezomib, lenalidomide, dexamethasone (VRd) given for approximately 3-4 cycles followed by autologous stem cell transplantation (ASCT). In high-risk patients, daratumumab, bortezomib, lenalidomide, dexamethasone (Dara-VRd) is an alternative to VRd. Selected standard-risk patients can collect stem cells, get additional cycles of induction therapy, and delay transplant until first relapse. Patients who are not candidates for transplant are treated with VRd for approximately 8-12 cycles followed by maintenance or alternatively with daratumumab, lenalidomide, dexamethasone (DRd) until progression.
MAINTENANCE THERAPY
Standard-risk patients need lenalidomide maintenance, while bortezomib plus lenalidomide maintenance is needed for high-risk myeloma.
MANAGEMENT OF RELAPSED DISEASE
A triplet regimen is usually needed at relapse, with the choice of regimen varying with each successive relapse.
Topics: Antineoplastic Combined Chemotherapy Protocols; Bortezomib; Dexamethasone; Hematopoietic Stem Cell Transplantation; Humans; Lenalidomide; Multiple Myeloma; Neoplasm Recurrence, Local; Risk Assessment; Transplantation, Autologous
PubMed: 35560063
DOI: 10.1002/ajh.26590 -
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 -
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 -
Leukemia Research Dec 2021Plasma cell leukemia is a rare and aggressive plasma cell dyscrasia associated with dismal outcomes. It may arise de novo, primary plasma cell leukemia, or evolve from... (Review)
Review
Plasma cell leukemia is a rare and aggressive plasma cell dyscrasia associated with dismal outcomes. It may arise de novo, primary plasma cell leukemia, or evolve from an antecedent diagnosis of multiple myeloma, secondary plasma cell leukemia. Despite highly effective therapeutics, survival for plasma cell leukemia patients remains poor. Molecular knowledge of plasma cell leukemia has recently expanded with use of gene expression profiling and whole exome sequencing, lending new insights into prognosis and therapeutic development. In this review, we describe the molecular knowledge, clinical characteristics, evidenced-based therapeutic approaches and treatment outcomes of plasma cell leukemia.
Topics: Evidence-Based Medicine; Humans; Leukemia, Plasma Cell
PubMed: 34425325
DOI: 10.1016/j.leukres.2021.106687 -
Blood May 2015Smoldering multiple myeloma (SMM) is an asymptomatic clonal plasma cell disorder. SMM is distinguished from monoclonal gammopathy of undetermined significance by a much... (Review)
Review
Smoldering multiple myeloma (SMM) is an asymptomatic clonal plasma cell disorder. SMM is distinguished from monoclonal gammopathy of undetermined significance by a much higher risk of progression to multiple myeloma (MM). There have been major advances in the diagnosis, prognosis, and management of SMM in the last few years. These include a revised disease definition, identification of several new prognostic factors, a classification based on underlying cytogenetic changes, and new treatment options. Importantly, a subset of patients previously considered SMM is now reclassified as MM on the basis of biomarkers identifying patients with an ≥80% risk of progression within 2 years. SMM has assumed greater significance on the basis of recent trials showing that early therapy can be potentially beneficial to patients. As a result, there is a need to accurately diagnose and risk-stratify patients with SMM, including routine incorporation of modern imaging and laboratory techniques. In this review, we outline current concepts in diagnosis and risk stratification of SMM, and provide specific recommendations on the management of SMM.
Topics: Asymptomatic Diseases; Clonal Evolution; Disease Management; Disease Progression; Humans; Multiple Myeloma; Risk Factors
PubMed: 25838344
DOI: 10.1182/blood-2014-09-568899 -
Virchows Archiv : An International... Jan 2023Plasma cell neoplasms including multiple myeloma (MM) and related terminally differentiated B-cell neoplasms are characterized by secretion of monoclonal immunoglobulin... (Review)
Review
Plasma cell neoplasms including multiple myeloma (MM) and related terminally differentiated B-cell neoplasms are characterized by secretion of monoclonal immunoglobulin and stepwise development from a preneoplastic clonal B and/or plasma cell proliferation called monoclonal gammopathy of undetermined significance (MGUS). Diagnosis of these disorders requires integration of clinical, laboratory, and morphological features. While their classification mostly remains unchanged compared to the revised 2016 WHO classification and the 2014 International Myeloma Working Group consensus, some changes in criteria and terminology were proposed in the 2022 International Consensus Classification (ICC) of mature lymphoid neoplasms. MGUS of IgM type is now divided into IgM MGUS of plasma cell type, precursor to the rare IgM MM and characterized by MM-type cytogenetics, lack of clonal B-cells and absence of MYD88 mutation, and IgM MGUS, NOS including the remaining cases. Primary cold agglutinin disease is recognized as a new entity. MM is now formally subdivided into cytogenetic groups, recognizing the importance of genetics for clinical features and prognosis. MM with recurrent genetic abnormalities includes MM with CCND family translocations, MM with MAF family translocations, MM with NSD2 translocation, and MM with hyperdiploidy, with the remaining cases classified as MM, NOS. For diagnosis of localized plasma cell tumors, solitary plasmacytoma of bone, and primary extraosseous plasmacytoma, the importance of excluding minimal bone marrow infiltration by flow cytometry is emphasized. Primary systemic amyloidosis is renamed immunoglobulin light chain amyloidosis (AL), and a localized AL amyloidosis is recognized as a distinct entity. This review summarizes the updates on plasma cell neoplasms and related entities proposed in the 2022 ICC. KEY POINTS: • Lymphoplasmacytic lymphoma can be diagnosed with lymphoplasmacytic aggregates in trephine biopsies < 10% of cellularity and evidence of clonal B-cells and plasma cells. • IgM MGUS is subdivided into a plasma cell type and a not otherwise specified (NOS) type. • Primary cold agglutinin disease is recognized as a new entity. • The term "multiple myeloma" replaces the term "plasma cell myeloma" used in the 2016 WHO classification. • Multiple myeloma is subdivided into 4 mutually exclusive cytogenetic groups and MM NOS. • Minimal bone marrow infiltration detected by flow cytometry is of major prognostic importance for solitary plasmacytoma of bone and to a lesser extent for primary extraosseous plasmacytoma. • Localized IG light chain amyloidosis is recognized as a separate entity, distinct from systemic immunoglobulin light chain (AL) amyloidosis.
Topics: Humans; Multiple Myeloma; Plasmacytoma; Paraproteinemias; Anemia, Hemolytic, Autoimmune; Monoclonal Gammopathy of Undetermined Significance; Amyloidosis; Lymphoma, B-Cell; Translocation, Genetic; Immunoglobulin M
PubMed: 36414803
DOI: 10.1007/s00428-022-03431-3 -
Clinical Medicine (London, England) Jan 2019
Review
Topics: Bone Marrow; Humans; Multiple Myeloma
PubMed: 30651246
DOI: 10.7861/clinmedicine.19-1-58 -
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 -
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