Journal ArticleDOI
Progression in Smoldering Myeloma Is Independently Determined by the Chromosomal Abnormalities del(17p), t(4;14), Gain 1q, Hyperdiploidy, and Tumor Load
Kai Neben,Anna Jauch,Thomas Hielscher,Jens Hillengass,Nicola Lehners,Anja Seckinger,Martin Granzow,Marc-Steffen Raab,Anthony D. Ho,Hartmut Goldschmidt,Dirk Hose +10 more
TLDR
The high-risk chromosomal aberrations del(17p13), t(4;14), and +1q21 are adverse prognostic factors in SMM just as they are in active myeloma, independent of tumor mass.Abstract:
Purpose The aim of this study was to analyze chromosomal aberrations in terms of frequency and impact on time to progression in patients with smoldering multiple myeloma (SMM) on the background of clinical prognostic factors. Patients and Methods The chromosomal abnormalities 1q21, 5p15/5q35, 9q34, 13q14.3, 15q22, 17p13, t(11;14)(q13;q32), and t(4;14)(p16.3;q32) were assessed in CD138-purified myeloma cells by interphase fluorescent in situ hybridization (iFISH) alongside clinical parameters in a consecutive series of 248 patients with SMM. Results The high-risk aberrations in active myeloma (ie, del(17p13), t(4;14), and +1q21) present in 6.1%, 8.9%, and 29.8% of patients significantly confer adverse prognosis in SMM with hazard ratios (HRs) of 2.90 (95% CI, 1.56 to 5.40), 2.28 (95% CI, 1.33 to 3.91), and 1.66 (95% CI, 1.08 to 2.54), respectively. Contrary to the conditions in active myeloma, hyperdiploidy, present in 43.3% of patients, is an adverse prognostic factor (HR, 1.67; 95% CI, 1.10 to 2.54). Per...read more
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International Myeloma Working Group updated criteria for the diagnosis of multiple myeloma.
S. Vincent Rajkumar,Meletios A. Dimopoulos,Antonio Palumbo,Joan Bladé,Giampaolo Merlini,Maria-Victoria Mateos,Shaji Kumar,Jens Hillengass,Efstathios Kastritis,Paul G. Richardson,Ola Landgren,Bruno Paiva,Angela Dispenzieri,Brendan M. Weiss,Xavier Leleu,Sonja Zweegman,Sagar Lonial,Laura Rosiñol,Elena Zamagni,Sundar Jagannath,O. Sezer,Sigurdur Y. Kristinsson,Jo Caers,Saad Z. Usmani,Juan José Lahuerta,Hans Erik Johnsen,Meral Beksac,Michele Cavo,Hartmut Goldschmidt,Evangelos Terpos,Robert A. Kyle,Kenneth C. Anderson,Brian G.M. Durie,Jesús F. San Miguel +33 more
TL;DR: The disease definition of multiple myeloma is updated to include validated biomarkers in addition to existing requirements of attributable CRAB features (hypercalcaemia, renal failure, anaemia, and bone lesions), and specific metrics that new biomarkers should meet for inclusion in the disease definition are provided.
Journal ArticleDOI
Multiple myeloma: 2020 update on diagnosis, risk-stratification and management.
TL;DR: Multiple myeloma accounts for approximately 10% of hematologic malignancies in the United States and is the second most common cancer in women.
Journal ArticleDOI
Multiple myeloma: 2016 update on diagnosis, risk-stratification, and management.
TL;DR: 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, serum involved/uninvolved free light chain (FLC) ratio, or >1 focal lesion on magnetic resonance imaging.
Journal ArticleDOI
Spatial genomic heterogeneity in multiple myeloma revealed by multi-region sequencing
Leo Rasche,Shweta S. Chavan,Owen W. Stephens,Purvi Patel,Ruslana Tytarenko,Cody Ashby,Michael A Bauer,Caleb K. Stein,Shayu Deshpande,Christopher P. Wardell,Timea Buzder,Gabor Molnar,Maurizio Zangari,F. van Rhee,Sharmilan Thanendrarajan,Carolina Schinke,Joshua Epstein,Faith E. Davies,Brian A Walker,Tobias Meissner,Bart Barlogie,Gareth J. Morgan,Niels Weinhold +22 more
TL;DR: It is suggested that multi-region investigations are critical to understanding intra-patient heterogeneity and the evolutionary processes in multiple myeloma, and the extent of spatial heterogeneity is positively associated with the size of biopsied focal lesions consistent with regional outgrowth of advanced clones.
Journal ArticleDOI
Target Expression, Generation, Preclinical Activity, and Pharmacokinetics of the BCMA-T Cell Bispecific Antibody EM801 for Multiple Myeloma Treatment
Anja Seckinger,Jose Antonio Delgado,Samuel Moser,Laura Moreno,Brigitte Neuber,Anna Luise Grab,Susanne Lipp,Juana Merino,Felipe Prosper,Martina Emde,Camille Delon,Melanie Latzko,Reto Gianotti,Remo Lüoend,Ramona Murr,Ralf Hosse,Lydia Jasmin Harnisch,Marina Bacac,Tanja Fauti,Christian Klein,Aintzane Zabaleta,Jens Hillengass,Elisabetta Ada Cavalcanti-Adam,Anthony D. Ho,Michael Hundemer,Jesús F. San Miguel,Klaus Strein,Pablo Umana,Dirk Hose,Bruno Paiva,Minh Diem Vu +30 more
TL;DR: An IgG-based BCMA-T cell bispecific antibody (EM801) was constructed and showed that it increased CD3+ T-cell/myeloma cell crosslinking, followed by CD4+/CD8+ T cell activation, and secretion of interferon-γ, granzyme B, and perforin, which is CD4 and CD8 T cell mediated.
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Criteria for the classification of monoclonal gammopathies, multiple myeloma and related disorders: a report of the International Myeloma Working Group
Robert A. Kyle,J. Anthony Child,Kenneth C. Anderson,Bart Barlogie,Régis Bataille,William I. Bensinger,Joan Bladé,Mario Boccadoro,William S. Dalton,Meletios A. Dimopoulos,Benjamin Djulbegovic,Mark T. Drayson,Brian G.M. Durie,Thiery Facon,Rafael Fonseca,Gösta Gahrton,Philip R. Greipp,Jean Luc Harousseau,David P. Harrington,Mohamad A. Hussein,Douglas E. Joshua,Heinz Ludwig,Gareth J. Morgan,Martin M. Oken,R. L. Powles,Paul G. Richardson,David Roodman,Jesús F. San Miguel,Kazuyuki Shimizu,Chaim Shustik,Bhawna Sirohi,Pieter Sonneveld,Guido J Tricot,Ingemar Turesson,Brian G Van Ness,David H. Vesole,Donna M. Weber,Jan Westin,Keith Wheatley +38 more
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