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First-line treatment of multiple myeloma in elderly patients: the GIMEMA (Gruppo Italiano Malattie EMatologiche dell'Adulto) multiple myeloma working party perspective.

Multiple myeloma (MM) is a neoplastic disorder affecting elderly people. The treatment for all patients with MM was, for about 40 years, based on the combination of melphalan plus prednisone, with a very low rate of complete remissions and a survival that remained unacceptably low (about 36 months). Diverse factors, including comorbidity, performance status, decreased physiologic reserve, and potential undertreatment, contribute to these poor outcomes. Recently, however, the reduced treatment-related morbidity and mortality associated with autologous stem-cell transplantation and the availabil…

[The Mechanism of Multiple Myeloma U266 Cell Exosome Circ- G042080 Promoting Multiple Myeloma Bone Disease through MiR-6791-3p/HDAC4 Axis].

OBJECTIVE: To explore the mechanism of multiple myeloma cell exosome circRNA inducing osteoclast differentiation and promoting myeloma bone disease, and explore the feasibility of intervening myeloma bone disease by regulating circRNA-mediated cell communication. METHODS: TargetScan, miRanda and dual luciferase reporter assays were used to predict and verify the downstream regulatory mechanism of circ-G042080. The exosomes of myeloma U266 cells were identified by electron microscopy. RANKL induced RAW264.7 cells to differentiate into osteoclasts. By co-culturing with U266 cells with or withou…

A Pooled Analysis of Reproductive Factors, Exogenous Hormone Use, and Risk of Multiple Myeloma among Women in the International Multiple Myeloma Consortium.

BACKGROUND: Female sex hormones are known to have immunomodulatory effects. Therefore, reproductive factors and exogenous hormone use could influence the risk of multiple myeloma in women. However, the role of hormonal factors in multiple myeloma etiology remains unclear because previous investigations were underpowered to detect modest associations. METHODS: We conducted a pooled analysis of seven case-control studies included in the International Multiple Myeloma Consortium, with individual data on reproductive factors and exogenous hormone use from 1,072 female cases and 3,541 female contr…

Risk of multiple myeloma and other malignancies among first- and second-degree relatives of patients with multiple myeloma: A population-based study.

OBJECTIVES: We conducted a population-based study to assess the risk for multiple myeloma (MM) and other cancers in first- and second-degree relatives of MM patients, and to investigate whether evidence of anticipation is present in familial MM. METHODS: We retrieved 24 845 first-degree relatives and 41 008 second-degree relatives of 7847 MM patients, and 86 984 first-degree relatives, and 138 660 second-degree relatives of 26 511 matched controls. A Cox model was used to assess the risk for MM and other cancers in relatives of MM patients. Anticipation was assessed by a Cox model, where all …

t(4;14), and revised myeloma comorbidity index as good predictors of survival for multiple myeloma.

BACKGROUND: Cytogenetic tests are essential prognostic indicators for patients diagnosed with multiple myeloma (MM). The study aimed to evaluate the prevalence of cytogenetic abnormalities and their prognostic significance in patients with newly diagnosed MM. RESEARCH DESIGN AND METHODS: A cohort study involving 88 cases. Malignant plasma cells were isolated, and interphase fluorescent in situ hybridization was performed on bone marrow samples. RESULTS: The gain of 1q was observed in 17 (19%) patients, followed by t(4;14) in 10 (11.5%), and the 17p or P53 mutation was found in only 6 (7%) pa…

The molecular make up of smoldering myeloma highlights the evolutionary pathways leading to multiple myeloma.

Smoldering myeloma (SMM) is associated with a high-risk of progression to myeloma (MM). We report the results of a study of 82 patients with both targeted sequencing that included a capture of the immunoglobulin and MYC regions. By comparing these results to newly diagnosed myeloma (MM) we show fewer NRAS and FAM46C mutations together with fewer adverse translocations, del(1p), del(14q), del(16q), and del(17p) in SMM consistent with their role as drivers of the transition to MM. KRAS mutations are associated with a shorter time to progression (HR 3.5 (1.5-8.1), p = 0.001). In an analysis of ch

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… Introduction Smoldering multiple myeloma (SMM) is an asymptomatic plasma cell disorder, distinguished from monoclonal gammopathy of undetermined significance (MGUS) by a higher rate of progression to symptomatic multiple myeloma (MM) 1 – 3 . … MMRF CoMMpass Network MYC dysregulation in the progression of multiple myeloma Leukemia 2020 34s 322 326 10.1038/s41375-019-0543-4 PMC6923575 31439946 12. Rosiñol L Comparative genomic hybridisation identifies two variants of smoldering multiple myeloma Br. J. …

Activin A promotes multiple myeloma-induced osteolysis and is a promising target for myeloma bone disease.

Understanding the pathogenesis of cancer-related bone disease is crucial to the discovery of new therapies. Here we identify activin A, a TGF-beta family member, as a therapeutically amenable target exploited by multiple myeloma (MM) to alter its microenvironmental niche favoring osteolysis. Increased bone marrow plasma activin A levels were found in MM patients with osteolytic disease. MM cell engagement of marrow stromal cells enhanced activin A secretion via adhesion-mediated JNK activation. Activin A, in turn, inhibited osteoblast differentiation via SMAD2-dependent distal-less homeobox-5 …

Multiple Myeloma: A Review of the Literature and a Case Report Highlighting the Immunocompromised State of Myeloma Patients.

Multiple myeloma (MM), a malignancy involving plasma cells, disproportionately affects older adults with an average age of diagnosis of about 70 years. Oftentimes, the therapies used in the treatment of MM are associated with a risk for immunotoxicity, lowering the ability of the immune system to fight off opportunistic infections. This is an important relationship for clinicians to realize as the incidence of opportunistic infections in myeloma patients is increasing. As an example, we present a case of a patient with MM who subsequently developed a cryptococcal infection. Our paper will high…

Stromal alterations in patients with monoclonal gammopathy of undetermined significance, smoldering myeloma, and multiple myeloma.

The hallmark of multiple myeloma (MM) is a clonal plasma cell infiltration in the bone marrow accompanied by myelosuppression and osteolysis. Premalignant stages such as monoclonal gammopathy of undetermined significance (MGUS) and asymptomatic stages such as smoldering myeloma (SMM) can progress to MM. Mesenchymal stromal cells (MSCs) are an integral component of the bone marrow microenvironment and play an important role in osteoblast differentiation and hematopoietic support. Although stromal alterations have been reported in MM contributing to hematopoietic insufficiency and osteolysis, it…

Allogeneic hematopoietic cell transplantation for multiple myeloma: A retrospective analysis of the Polish Myeloma Group.

PURPOSE: In this multicenter retrospective analysis of the Polish Myeloma Group we assessed the real-life application of allogeneic transplantations (alloHCT) in multiple myeloma (MM) outside clinical trials in Poland. METHODS: Anonymized clinical data of patients who underwent alloHCT were retrospectively collected from eight transplant centers and analyzed to identify factors affecting the outcome. RESULTS: Sixty patients (34 males, 26 females) at median age of 45 (22-59) years who received alloHCT between 1993 and 2016 were included. In this group, 16 (27%) patients underwent myeloablativ…

Best Practice for the Administration of Daratumumab in Multiple Myeloma: Australian Myeloma Nurse Expert Opinion.

Patients with multiple myeloma (MM) are typically of an advanced age and may have significant co-existing medical conditions. They have often had multiple lines of therapy and as such experience disease-related effects alongside associated treatment toxicities. Daratumumab is a monoclonal antibody approved for the treatment of MM in the relapsed/refractory setting. Clinical studies found that daratumumab showed good tolerability as a monotherapy and in combination with current standard therapies. However, the administration of daratumumab does require specific management considerations. It is …

European Myeloma Network recommendations on the evaluation and treatment of newly diagnosed patients with multiple myeloma.

Multiple myeloma management has undergone profound changes in the past thanks to advances in our understanding of the disease biology and improvements in treatment and supportive care approaches. This article presents recommendations of the European Myeloma Network for newly diagnosed patients based on the GRADE system for level of evidence. All patients with symptomatic disease should undergo risk stratification to classify patients for International Staging System stage (level of evidence: 1A) and for cytogenetically defined high- versus standard-risk groups (2B). Novel-agent-based induction…

Abnormal radiological features in a multiple myeloma patient: a case report and radiological review of myelomas.

Multiple myeloma is the prototype of malignant monoclonal gammopathies. The most common skeletal sites are pelvis, skull, spine, ribs and femoral and humeral shafts. The classic radiographic presentation of multiple myeloma is lytic skeletal lesions. Other types of presentation include sclerotic and porotic changes. Primary sclerotic manifestations are rare and occur in only 3% of cases. Although exceptional, multiple myeloma must be borne in mind in the presence of bone sclerosis. This report presents a patient with multiple myeloma with a sunburst/hair-on-end pattern on the radiograph and sc…

The use of bisphosphonates in multiple myeloma: recommendations of an expert panel on behalf of the European Myeloma Network.

BACKGROUND: Bisphosphonates (BPs) prevent, reduce, and delay multiple myeloma (MM)-related skeletal complications. Intravenous pamidronate and zoledronic acid, and oral clodronate are used for the management of MM bone disease. The purpose of this paper is to review the current evidence for the use of BPs in MM and provide European Union-specific recommendations to support the clinical practice of treating myeloma bone disease. DESIGN AND METHODS: An interdisciplinary, expert panel of specialists on MM and myeloma-related bone disease convened for a face-to-face meeting to review and assess t…

Report of the European Myeloma Network on multiparametric flow cytometry in multiple myeloma and related disorders.

The European Myeloma Network (EMN) organized two flow cytometry workshops. The first aimed to identify specific indications for flow cytometry in patients with monoclonal gammopathies, and consensus technical approaches through a questionnaire-based review of current practice in participating laboratories. The second aimed to resolve outstanding technical issues and develop a consensus approach to analysis of plasma cells. The primary clinical applications identified were: differential diagnosis of neoplastic plasma cell disorders from reactive plasmacytosis; identifying risk of progression in

International myeloma working group immunotherapy committee recommendation on sequencing immunotherapy for treatment of multiple myeloma.

T-cell redirecting therapy (TCRT), specifically chimeric antigen receptor T-cell therapy (CAR T-cells) and bispecific T-cell engagers (TCEs) represent a remarkable advance in the treatment of multiple myeloma (MM). There are several products available around the world and several more in development targeting primarily B-cell maturation antigen (BCMA) and G protein-coupled receptor class C group 5 member D (GRPC5D). The relatively rapid availability of multiple immunotherapies brings the necessity to understand how a certain agent may affect the safety and efficacy of a subsequent immunotherap…