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Smoldering myeloma

Carolina Schinke, Pingping Qu, Syed J Mehdi, Antje Hoering, Joshua Epstein, Sarah Johnson, Frits van Rhee, Maurizio Zangari, Sharmilan Thanendrarajan, Bart Barlogie, Faith E Davies, Shmuel Yaccoby, Gareth Morgan
PURPOSE: Mesenchymal stem cells (MSCs) are an essential component of the bone marrow (BM) microenvironment and have shown to support cancer evolution in multiple myeloma (MM). Despite the increasing evidence that MM MSCs differ from their healthy counterparts, little knowledge exists as to whether MSCs independently influence disease outcome. The aim of the present study was to determine the importance of MSCs in disease progression and outcome in MM. EXPERIMENTAL DESIGN: To determine the impact of MSCs on MM outcome in an in vivo system, we first identified genes from cultured MSCs that were specific to MSC expression and were not or minimally expressed in PCs or other cells present in BM aspirates...
March 21, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Yue Yang, Long Chen, Yuan Jia, Yang Liu, Lei Wen, Yaoxian Liang, Yuan An, Shi Chen, Yin Su, Zhanguo Li
To analyze the clinical spectrum, laboratory characteristics, and outcomes of monoclonal gammopathy (MG) in patients with rheumatic diseases. Screening for the presence of MG was performed in 872 inpatients with rheumatic diseases from January 2010 to July 2017. A total of 41 patients were enrolled. Their clinical and biological features in addition to outcomes were described. For each patient with primary Sjögren syndrome (pSS), 2 age- and sex-matched pSS patients without MG were selected as controls. Risk factors for the presence of MG and malignant hematological neoplasias were assessed...
March 13, 2018: Clinical Rheumatology
Charlotte Pawlyn, Andrea Loehr, Cody Ashby, Ruslana Tytarenko, Shayu Deshpande, James Sun, Kyle Fedorchak, Tariq Mughal, Faith E Davies, Brian A Walker, Gareth J Morgan
PARP inhibitors can induce synthetic lethality in tumors characterized by homologous recombination deficiency (HRD), which can be detected by evaluating genome-wide loss of heterozygosity (LOH). Multiple myeloma (MM) is a genetically unstable tumor and we hypothesized that HRD-related LOH (HRD-LOH) could be detected in patient samples, supporting a potential role for PARP inhibition in MM. Using results from targeted next-generation sequencing studies (FoundationOne® Heme), we analyzed HRD-LOH in patients at all disease stages (MGUS (n = 7), smoldering MM (SMM, n = 30), newly diagnosed MM (NDMM, n = 71), treated MM (TRMM, n = 64), and relapsed MM (RLMM, n = 234)) using an algorithm to identify HRD-LOH segments...
February 2, 2018: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
Carlos Fernández de Larrea, Ignacio Isola, Arturo Pereira, Ma Teresa Cibeira, Laura Magnano, Natalia Tovar, Luis-Gerardo Rodríguez-Lobato, Xavier Calvo, Juan I Aróstegui, Tania Díaz, Ester Lozano, María Rozman, Jordi Yagüe, Joan Bladé, Laura Rosiñol
Smoldering multiple myeloma (SMM) is a biologically heterogeneous, clinically defined entity with a variable rate of progression to symptomatic multiple myeloma (MM). Reliable markers for progression are critical for the development of potential therapeutic interventions. We retrospectively evaluated the predictive value of the evolving pattern of serum M-protein among other progression risk factors in 206 patients with SMM diagnosed between 1973 and 2012. Median time from recognition of evolving type to progression into symptomatic MM was 1...
February 2, 2018: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
Bita Fakhri, Mark A Fiala, Sascha A Tuchman, Tanya M Wildes
BACKGROUND: With the expanding armamentarium of therapeutic agents for multiple myeloma (MM), it is important to identify any undertreated patient populations to mitigate outcome disparities. MATERIALS AND METHODS: We extracted the data for all plasma cell myeloma cases (International Classification of Disease for Oncology, third revision [ICD-O-3] code 9732) in the Surveillance, Epidemiology, End Results (SEER)-Medicare database from 2007 to 2011. The ICD-O-3 histologic code 9732 captures both active MM and smoldering/asymptomatic myeloma...
January 31, 2018: Clinical Lymphoma, Myeloma & Leukemia
Masahiro Chiba, Kazuo Oshimi, Toshihiro Matsukawa, Kouhei Okada, Takuto Miyagishima
A 68-year-old female with smoldering multiple myeloma (IgG-κ type) was admitted to the hospital owing to general fatigue, fever, and pain in the right leg. On the day following admission, she developed shock, and a blood culture revealed Streptococcus pneumoniae. She was diagnosed with septic shock and invasive pneumococcal disease (IPD). She received antibiotics and intravenous immunoglobulin and improved after several days. She had a history of recurrent IPD and had received the pneumococcal polysaccharide vaccine 23 (PPSV23) 2 years earlier...
2018: [Rinshō Ketsueki] the Japanese Journal of Clinical Hematology
Vassilis Koutoulidis, Nickolas Papanikolaou, Lia A Moulopoulos
MRI plays an important role in the management of patients with plasma cell neoplasms and has been recognized as a biomarker of malignancy in the novel criteria for the diagnosis of multiple myeloma. Functional and molecular MRI techniques such as Diffusion-Weighted Imaging (Spinal or Whole Body), Intravoxel Incoherent Motion, and Dynamic Contrast-Enhanced MRI, provide additional information related to tumor cellularity and angiogenesis, which may have prognostic implications for patients with smoldering and symptomatic myeloma...
February 2, 2018: British Journal of Radiology
Roberto Ria, Franco Dammacco, Angelo Vacca
The heavy chain diseases (HCDs) are rare B-cell malignancies characterized by the production of a monoclonal immunoglobulin heavy chain without an associated light chain. There are three types of HCD, defined by the class of immunoglobulin heavy chain produced: IgA (α-HCD), IgG (γ-HCD), and IgM (μ-HCD). Alpha-HCD is the most common and usually occurs as intestinal malabsorption in a young adult from a country of the Mediterranean area. Gamma- and μ-HCDs are rarer and associated with a B-cell non-Hodgkin lymphoma that produces an abnormal Ig heavy chain...
2018: Mediterranean Journal of Hematology and Infectious Diseases
Wilson I Gonsalves, Vijay Ramakrishnan, Taro Hitosugi, Toshi Ghosh, Dragan Jevremovic, Tumpa Dutta, Dhananjay Sakrikar, Xuan-Mai Petterson, Linda Wellik, Shaji K Kumar, K Sreekumaran Nair
The production of the oncometabolite 2-hydroxyglutarate (2-HG) has been associated with c-MYC overexpression. c-MYC also regulates glutamine metabolism and drives progression of asymptomatic precursor plasma cell (PC) malignancies to symptomatic multiple myeloma (MM). However, the presence of 2-HG and its clinical significance in PC malignancies is unknown. By performing 13C stable isotope resolved metabolomics (SIRM) using U[13C6]Glucose and U[13C5]Glutamine in human myeloma cell lines (HMCLs), we show that 2-HG is produced in clonal PCs and is derived predominantly from glutamine anaplerosis into the TCA cycle...
January 11, 2018: JCI Insight
Sham Mailankody, Dickran Kazandjian, Neha Korde, Mark Roschewski, Elisabet Manasanch, Manisha Bhutani, Nishant Tageja, Mary Kwok, Yong Zhang, Adriana Zingone, Laurence Lamy, Rene Costello, Candis Morrison, Malin Hultcrantz, Austin Christofferson, Megan Washington, Martin Boateng, Seth M Steinberg, Maryalice Stetler-Stevenson, William D Figg, Elli Papaemmanuil, Wyndham H Wilson, Jonathan J Keats, Ola Landgren
Early results of a prospective phase 2 clinical trial of carfilzomib, lenalidomide, and dexamethasone followed by lenalidomide maintenance in high-risk smoldering myeloma showed promising results that were previously published. Here, we provide novel insights into the genetic landscape of high-risk smoldering myeloma and information on sustained minimal residual disease (MRD) negativity with an expanded cohort of patients. Eighteen patients with high-risk smoldering myeloma were enrolled between 29 May 2012, and 14 January 2014...
October 10, 2017: Blood Advances
Ola Landgren
In recent years, several new drugs have been approved for the treatment of multiple myeloma. Many of these newer drugs are highly efficacious and less toxic than older chemotherapy drugs. In 2014, the diagnostic criteria for multiple myeloma were revised. The intent with the new criteria was to identify patients who require therapy at an earlier stage than at manifestation of organ complications. A subset of patients who were previously defined as having high-risk smoldering multiple myeloma was redefined as having multiple myeloma...
December 8, 2017: Hematology—the Education Program of the American Society of Hematology
Mathilde Bahuaud, Hélène Bodilis, Marion Malphettes, Anaïs Maugard Landre, Caroline Matondo, Didier Bouscary, Frédéric Batteux, Odile Launay, Jean-Paul Fermand
Smoldering multiple myeloma (SMM) is an asymptomatic clonal plasma cell disorder that frequently progress to multiple myeloma (MM), a disease at high risk of pneumococcal infections. Moreover, if the polysaccharide vaccine is poorly immunogenic in MM, the 13-valent conjugated vaccine has never been tested in clonal plasma cell disorders. We evaluated its immunogenicity for 7 serotypes in 20 patients ≥ 50 years of age with smoldering multiple myeloma (SMM) pre and post routine-vaccination with PCV13. Concentrations of IgG specific for 7 serotypes were measured at baseline, 1, 6, and 12 months after vaccination by standardized ELISA and an Opsonophagocytic Assay (OPA)...
November 2017: Heliyon
Niels W C J van de Donk, Paul G Richardson, Fabio Malavasi
CD38 is highly and uniformly expressed on multiple myeloma (MM) cells, and at relatively low levels on normal lymphoid and myeloid cells, and in some tissues of nonhematopoietic origin. CD38 is a transmembrane glycoprotein with ectoenzymatic activity, and also functions as a receptor and adhesion molecule. Altogether, this has triggered the development of several CD38 antibodies including daratumumab (fully human), isatuximab (chimeric), and MOR202 (fully human). CD38 antibodies have pleiotropic mechanisms of action including Fc-dependent immune-effector mechanisms, direct apoptotic activity, and immunomodulatory effects by the elimination of CD38+ immune-suppressor cells...
January 4, 2018: Blood
María-Victoria Mateos
No abstract text is available yet for this article.
October 2017: Clinical Advances in Hematology & Oncology: H&O
O Gutwein, N Rahimi-Levene, K Herzog-Tzarfati, O Garach-Jehoshua, A Nagler, M Izak, M Koren-Michowitz
Patients with multiple myeloma (MM) have an increased thrombotic risk, but pathogenesis remains uncertain. Low levels of Protein Z (PZ), a vitamin K-dependent plasma protein, are associated with venous as well as arterial thrombosis. The purpose of this study was to analyze PZ levels in patients with plasma cell neoplasms. PATIENTS AND METHODS: The study consisted of 64 plasma cells neoplasm patients and 42 healthy individuals. Clinical investigations included measurement of plasma PZ and IL-6 levels...
November 2017: Leukemia Research
Adrien Bosseboeuf, Delphine Feron, Anne Tallet, Cédric Rossi, Cathy Charlier, Laurent Garderet, Denis Caillot, Philippe Moreau, Marina Cardó-Vila, Renata Pasqualini, Wadih Arap, Alfreda Destea Nelson, Bridget S Wilson, Hélène Perreault, Eric Piver, Pierre Weigel, François Girodon, Jean Harb, Edith Bigot-Corbel, Sylvie Hermouet
Subsets of mature B cell neoplasms are linked to infection with intracellular pathogens such as Epstein-Barr virus (EBV), hepatitis C virus (HCV), or Helicobacter pylori. However, the association between infection and the immunoglobulin-secreting (Ig-secreting) B proliferative disorders remains largely unresolved. We investigated whether the monoclonal IgG (mc IgG) produced by patients diagnosed with monoclonal gammopathy of undetermined significance (MGUS) or multiple myeloma (MM) targets infectious pathogens...
October 5, 2017: JCI Insight
Sabrina Manni, Marilena Carrino, Francesco Piazza
Multiple myeloma (MM) is a malignant tumor of transformed plasma cells. MM pathogenesis is a multistep process. This cancer can occur de novo (rarely) or it can develop from monoclonal gammopathy of undetermined significance (most of the cases). MM can be asymptomatic (smoldering myeloma) or clinically active. Malignant plasma cells exploit intrinsic and extrinsic bone marrow microenvironment-derived growth signals. Upregulation of stress-coping pathways is also instrumental to maintain MM cell growth. The phylogenetically related Ser/Thr kinases CSNK1A1 (CK1α) and CSNK2 (CK2) have recently gained a growing importance in hematologic malignancies arising both from precursors and from mature blood cells...
October 2, 2017: Journal of Hematology & Oncology
Christine Greil, Gabriele Ihorst, Felix Gaiser, Ulrich Salzer, Emanuel Bisse, Efstathios Kastritis, Heinz Ludwig, Ralph Wäsch, Monika Engelhardt
OBJECTIVE: The heavy/light chain (HLC)-immunoassay quantifies light chain types of each immunoglobulin class in patients with monoclonal gammopathies. METHODS: We assessed 147 consecutive patients with different forms and stages of plasma cell dyscrasias (PCD) who received standard tests (serum and urine protein electrophoresis [SPEP, UPEP], immunofixation [IFE], serum-free light chain [SFLC]), and HLC-immunoassay. Patients with multiple myeloma (MM, n = 102), smoldering MM (SMM, n = 5), monoclonal gammopathy of undetermined significance (MGUS, n = 28), and Waldenström's macroglobulinemia (WM, n = 12) were included...
September 8, 2017: European Journal of Haematology
J Hillengass, L A Moulopoulos, S Delorme, V Koutoulidis, J Mosebach, T Hielscher, M Drake, S V Rajkumar, B Oestergaard, N Abildgaard, M Hinge, T Plesner, Y Suehara, K Matsue, N Withofs, J Caers, A Waage, H Goldschmidt, M A Dimopoulos, S Lentzsch, B Durie, E Terpos
For decades, conventional skeletal survey (CSS) has been the standard imaging technique for multiple myeloma (MM). However, recently whole-body computed tomography (WBCT) has been implemented into the diagnostic criteria of MM. This analysis compares sensitivity and prognostic significance of WBCT and CSS in patients with smoldering MM (SMM) and MM. Fifty-four of 212 patients (25.5%) had a negative CSS and a positive WBCT for osteolytic lesions (P<0.0001). Of 66 patients with SMM based on CSS, 12 (22.2%) had osteolytic lesions on WBCT...
August 25, 2017: Blood Cancer Journal
Michael Kehrer, Sebastian Koob, Andreas Strauss, Dieter Christian Wirtz, Jan Schmolders
Background Multiple myeloma is a haematological blood cancer of the bone marrow and is classified by the World Health Organisation (WHO) as a plasma cell neoplasm. In multiple myeloma, normal plasma cells transform into malignant myeloma cells and produce large quantities of an abnormal immunoglobulin called monoclonal protein or M protein. This ultimately causes multiple myeloma symptoms such as bone damage or kidney problems. The annual worldwide incidence of multiple myeloma is estimated to be 6 - 7/100,000 and accounts for 1% of all cancer...
October 2017: Zeitschrift Für Orthopädie und Unfallchirurgie
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