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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 -
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 -
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 -
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 -
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 -
Clinical Lymphoma, Myeloma & Leukemia May 2023Monoclonal Gammopathy of Undetermined Significance (MGUS) is an asymptomatic premalignant plasma cell dyscrasia with a predominate rise of the IgG immunoglobulin... (Review)
Review
Monoclonal Gammopathy of Undetermined Significance (MGUS) is an asymptomatic premalignant plasma cell dyscrasia with a predominate rise of the IgG immunoglobulin fraction without end-organ damage, often diagnosed incidentally. Despite its progression into various subsequent forms of hematological malignancies, MGUS remains underdiagnosed. A literature search was conducted using the Medline, Cochrane, Embase, and Google Scholar databases, including articles published until December 2022. Keywords used encompassed "Monoclonal Gammopathy of Undetermined Significance," "Plasma Cell dyscrasia," "Monoclonal gammopathy of renal significance," and "IgM Monoclonal gammopathy of Undetermined Significance," This study aimed to conduct a critical review to update knowledge regarding the pathophysiology, risk factors, clinical features, diagnostic protocols, complications, and current and novel treatments for MGUS. We recommend a multidisciplinary approach to manage MGUS due to the complexity of the illness's etiology, diagnosis, and therapy. This comprehensive review also highlights future prospects, such as developing screening protocols for at-risk populations, prevention of disease progression by early diagnosis through genome-wide association studies, and management using Daratumumab and NSAIDs.
Topics: Humans; Monoclonal Gammopathy of Undetermined Significance; Genome-Wide Association Study; Paraproteinemias; Risk Factors; Neoplasms, Plasma Cell; Multiple Myeloma; Disease Progression
PubMed: 36966041
DOI: 10.1016/j.clml.2023.02.004 -
Leukemia May 2023Multiple Myeloma (MM) remains an incurable plasma cell neoplasm. Although little is known about the etiology of MM, several metabolic risk factors such as obesity,... (Review)
Review
Multiple Myeloma (MM) remains an incurable plasma cell neoplasm. Although little is known about the etiology of MM, several metabolic risk factors such as obesity, diabetes mellitus, diet, and the human intestinal microbiome have been linked to the pathogenesis of MM. In this article, we provide a detailed review of dietary and microbiome factors involved in the pathogenesis of MM and their impact on outcomes. Concurrent with treatment advancements that have improved survival in MM, focused efforts are needed to reduce the burden of MM as well as improve MM specific and overall outcomes once MM is diagnosed. The findings presented in this review will provide a comprehensive guide on the evidence available to date of the impact of dietary and other lifestyle interventions on the gut microbiome and on MM incidence, outcomes, and quality of life. Data generated from such studies can help formulate evidence-based guidelines for healthcare providers to counsel individuals at risk such as those with Monoclonal Gammopathy of Undetermined Significance (MGUS) and Smoldering Multiple Myeloma (SMM) as well as MM survivors with respect to their dietary habits.
Topics: Humans; Multiple Myeloma; Plasma Cells; Quality of Life; Paraproteinemias; Diet; Microbiota
PubMed: 36997677
DOI: 10.1038/s41375-023-01874-4 -
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 -
Current Hematologic Malignancy Reports Apr 2020As novel therapies are expanding the life expectancy of patients with multiple myeloma, appropriate supportive care has become critical in the management of these... (Review)
Review
PURPOSE OF REVIEW
As novel therapies are expanding the life expectancy of patients with multiple myeloma, appropriate supportive care has become critical in the management of these patients. This review aims to outline the key principles of supportive care of patients with myeloma, including management of bone disease, renal disease, anemia, peripheral neuropathy, infections, and venous thromboembolism.
RECENT FINDINGS
The results from large randomized, controlled trials on the use of high-cutoff hemodialysis in the removal of free light chains in renal disease and the use of levofloxacin in the prevention of infections have recently been published. These results, along with updated guidelines from professional societies on the use of bisphosphonates and erythropoietin stimulating agents, have provided guidance on more effective management strategies for myeloma patients. Integration of these updated guidelines and supportive care strategies into clinical practice will help to ensure quality of life for patients with myeloma.
Topics: Humans; Multiple Myeloma; Palliative Care; Quality of Life; Treatment Outcome
PubMed: 32172361
DOI: 10.1007/s11899-020-00570-9