Sabina Sevcikova, Jiri Minarik, Martin Stork, Tomas Jelinek, Ludek Pour, Roman Hajek
Extramedullary disease of multiple myeloma (EM) remains a treatment challenge even in the era of new drugs. While many reports analyzing various aspects of EM have been published, mechanism of EM development has not been clarified yet. This review summarizes current knowledge about this clinical entity, including its history, diagnostics, imaging methods, incidence, prognosis, current treatment options, risk factors and known molecular mechanisms that might be involved in pathogenesis of EM.
July 2019: Blood Reviews
Chris Plummer, Christoph Driessen, Zsolt Szabo, María-Victoria Mateos
Multiple myeloma (MM) is a plasma cell malignancy that accounts for 10% of hematological cancers. It predominantly affects elderly people; median age at diagnosis is 70 years. Consequently, many patients with MM have cardiovascular comorbidities or risk factors. MM can cause cardiac comorbidities such as cardiomyopathy and heart failure caused by cardiac amyloidosis and/or anemia. Some of the treatments used in MM can also affect cardiovascular health. Advances in pharmacotherapy for MM, such as the introduction of immunomodulators, proteasome inhibitors, histone deacetylase inhibitors, and monoclonal antibodies, have dramatically improved progression-free survival and life expectancy, but new agent classes are associated with adverse events that were not previously observed on a regular basis, including cardiovascular events...
February 26, 2019: Blood Cancer Journal
Hartmut Goldschmidt, John Ashcroft, Zsolt Szabo, Laurent Garderet
Multiple myeloma is one of the most common hematological malignancies, affecting mainly elderly patients. The treatment landscape for the management of this disease has evolved significantly over the past 15 years, and a vast array of therapeutics is now available, including immunomodulatory drugs, proteasome inhibitors, histone deacetylase inhibitors, and monoclonal antibodies. As a result, deciding which drugs to use and when, and whether these should be used in a particular order or combination, can be challenging...
January 2019: Annals of Hematology
Dawn Swan, Alberto Rocci, Charlotte Bradbury, Jecko Thachil
Multiple myeloma is associated with a significant risk of venous thromboembolism (VTE), causing substantial levels of morbidity and mortality. The thrombogenicity of myeloma is multifactorial, with disease- and treatment-related factors playing important roles. Immunomodulatory drugs (IMiDs) and high-dose dexamethasone, in particular, are known to enhance the thrombotic potential of myeloma. For this reason, assessment of the VTE risk has long been advocated prior to treatment initiation in patients with myeloma requiring IMiD-based regimens...
November 2018: British Journal of Haematology
Jo Caers, Laurent Garderet, K Martin Kortüm, Michael E O'Dwyer, Niels W C J van de Donk, Mascha Binder, Sandra Maria Dold, Francesca Gay, Jill Corre, Yves Beguin, Heinz Ludwig, Alessandra Larocca, Christoph Driessen, Meletios A Dimopoulos, Mario Boccadoro, Martin Gramatzki, Sonja Zweegman, Hermann Einsele, Michele Cavo, Hartmut Goldschmidt, Pieter Sonneveld, Michel Delforge, Holger W Auner, Evangelos Terpos, Monika Engelhardt
The diagnosis of multiple myeloma can be challenging, even for experienced physicians, and requires close collaboration between numerous disciplines (orthopedics, radiology, nuclear medicine, radiation therapy, hematology and oncology) before the final diagnosis of myeloma is made. The definition of multiple myeloma is based on the presence of clinical, biochemical, histopathological, and radiological markers of disease. Specific tests are needed both at presentation and during follow-up in order to reach the correct diagnosis and characterize the disease precisely...
November 2018: Haematologica
Maria Gavriatopoulou, Pellegrino Musto, Jo Caers, Giampaolo Merlini, Efstathios Kastritis, Niels van de Donk, Francesca Gay, Ute Hegenbart, Roman Hajek, Sonja Zweegman, Benedetto Bruno, Christian Straka, Meletios A Dimopoulos, Hermann Einsele, Mario Boccadoro, Pieter Sonneveld, Monika Engelhardt, Evangelos Terpos
The introduction of novel agents in the management of multiple myeloma and related plasma cell dyscrasias has changed our treatment approaches and subsequently the outcome of patients. Due to current advances, the European Myeloma Network updated the diagnostic and therapeutic recommendations for patients with Waldenström's macroglobulinemia (WM), AL-amyloidosis, monoclonal immunoglobulin deposition disease (MIDD), POEMS syndrome, and primary plasma cell leukemia. For patients with WM, the combination of rituximab with chemotherapy remains the treatment cornerstone, while the Bruton-tyrosine kinase inhibitor ibrutinib has been introduced and approved for relapsed/refractory disease...
September 2018: Leukemia
Hanley N Abramson
Treatment of multiple myeloma (MM), a neoplasm of plasma cells, formerly dependent on alkylating drugs, corticosteroids, and autologous stem cell transplantation, has changed dramatically in the past 20 years because 3 new classes of small molecule drugs (arbitrarily defined as having a molecular weight of < 900 kDa)-immunomodulators, proteasome inhibitors, and histone deacetylase blockers-have been introduced for the disease. Therapeutic options for MM expanded further in 2015 when 2 new monoclonal antibodies (daratumumab and elotuzumab) were approved by the Food and Drug Administration for MM...
September 2018: Clinical Lymphoma, Myeloma & Leukemia
Heinz Ludwig, Michel Delforge, Thierry Facon, Hermann Einsele, Francesca Gay, Philippe Moreau, Hervé Avet-Loiseau, Mario Boccadoro, Roman Hajek, Mohamad Mohty, Michele Cavo, Meletios A Dimopoulos, Jesús F San-Miguel, Evangelos Terpos, Sonja Zweegman, Laurent Garderet, María-Victoria Mateos, Gordon Cook, Xavier Leleu, Hartmut Goldschmidt, Graham Jackson, Martin Kaiser, Katja Weisel, Niels W C J van de Donk, Anders Waage, Meral Beksac, Ulf H Mellqvist, Monika Engelhardt, Jo Caers, Christoph Driessen, Joan Bladé, Pieter Sonneveld
During the last few years, several new drugs have been introduced for treatment of patients with multiple myeloma, which have significantly improved the treatment outcome. All of these novel substances differ at least in part in their mode of action from similar drugs of the same drug class, or are representatives of new drug classes, and as such present with very specific side effect profiles. In this review, we summarize these adverse events, provide information on their prevention, and give practical guidance for monitoring of patients and for management of adverse events...
July 2018: Leukemia
Robert A Kyle, Dirk R Larson, Terry M Therneau, Angela Dispenzieri, Shaji Kumar, James R Cerhan, S Vincent Rajkumar
BACKGROUND: Monoclonal gammopathy of undetermined significance (MGUS) occurs in approximately 3% of persons 50 years of age or older. METHODS: We studied 1384 patients who were residing in southeastern Minnesota and in whom MGUS was diagnosed at the Mayo Clinic in the period from 1960 through 1994; the median follow-up was 34.1 years (range, 0.0 to 43.6). The primary end point was progression to multiple myeloma or another plasma-cell or lymphoid disorder. RESULTS: During 14,130 person-years of follow-up, MGUS progressed in 147 patients (11%), a rate that was 6...
January 18, 2018: New England Journal of Medicine
C S Chim, S K Kumar, R Z Orlowski, G Cook, P G Richardson, M A Gertz, S Giralt, M V Mateos, X Leleu, K C Anderson
Despite enormous advances, management of multiple myeloma (MM) remains challenging. Multiple factors impact the decision to treat or which regimen to use at MM relapse/progression. Recent major randomized controlled trials (RCTs) showed widely varying progression-free survivals (PFS), ranging from a median of 4 months (MM-003) to 23.6 months (ASPIRE). Based on these RCTs, next-generation proteasome inhibitors (carfilzomib and ixazomib), next-generation immunomodulatory agent (pomalidomide), and monoclonal antibodies (elotuzumab and daratumumab) were approved for relapsed and refractory MM...
February 2018: Leukemia
Philippe Moreau
At present, multiple classes of agents with distinct mechanisms of action are available for the treatment of patients with multiple myeloma (MM), including alkylators, steroids, immunomodulatory agents (IMiDs), proteasome inhibitors (PIs), histone deacetylase inhibitors (DACIs), and monoclonal antibodies (mAbs). Over the last 5 years, several new agents, such as the third-generation IMiD pomalidomide, the second-generation PIs carfilzomib and ixazomib, the DACI panobinostat, and 2 mAbs, elotuzumab and daratumumab, have been approved, incorporated into clinical guidelines, and have transformed our approach to the treatment of patients...
September 28, 2017: Blood
Jean Luc Harousseau, Michel Attal
The standard treatment of relapsed multiple myeloma has been either lenalidomide-dexamethasone (RD) or bortezomib-dexamethasone (VD) but it is changing rapidly for 2 reasons. First, lenalidomide and bortezomib are currently used in frontline treatment and many patients become resistant to these agents early in the course of their disease. Second, 6 second-line new agents have been recently developed and offer new possibilities (pomalidomide, carfilzomib and ixazomib, panobinostat, elotuzumab, and daratumumab)...
August 24, 2017: Blood
P Moreau, J San Miguel, P Sonneveld, M V Mateos, E Zamagni, H Avet-Loiseau, R Hajek, M A Dimopoulos, H Ludwig, H Einsele, S Zweegman, T Facon, M Cavo, E Terpos, H Goldschmidt, M Attal, C Buske
No abstract text is available yet for this article.
July 1, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
David Dingli, Sikander Ailawadhi, P Leif Bergsagel, Francis K Buadi, Angela Dispenzieri, Rafael Fonseca, Morie A Gertz, Wilson I Gonsalves, Susan R Hayman, Prashant Kapoor, Taxiarchis Kourelis, Shaji K Kumar, Robert A Kyle, Martha Q Lacy, Nelson Leung, Yi Lin, John A Lust, Joseph R Mikhael, Craig B Reeder, Vivek Roy, Stephen J Russell, Taimur Sher, A Keith Stewart, Rahma Warsame, Stephen R Zeldenrust, S Vincent Rajkumar, Asher A Chanan Khan
Life expectancy in patients with multiple myeloma is increasing because of the availability of an increasing number of novel agents with various mechanisms of action against the disease. However, the disease remains incurable in most patients because of the emergence of resistant clones, leading to repeated relapses of the disease. In 2015, 5 novel agents were approved for therapy for relapsed multiple myeloma. This surfeit of novel agents renders management of relapsed multiple myeloma more complex because of the occurrence of multiple relapses, the risk of cumulative and emergent toxicity from previous therapies, as well as evolution of the disease during therapy...
April 2017: Mayo Clinic Proceedings
Michel Delforge, Heinz Ludwig
The treatment of multiple myeloma is considered a continuously evolving paradigm as a result of the growing availability of new and highly effective drugs, including first- and second-generation proteasome inhibitors, immunomodulatory agents, and monoclonal antibodies. Clinical trials advocate long-term rather than short-term treatment schedules with combinations of these new anti-myeloma drug classes. Although the overall toxicity profile of the recommended regimens can be considered favorable, their increasing complexity and prolonged use warrant a heightened vigilance for early and late side effects, a priori because real-life patients can be more frail or present with 1 or more comorbidities...
April 27, 2017: Blood
Brian G M Durie, Antje Hoering, Muneer H Abidi, S Vincent Rajkumar, Joshua Epstein, Stephen P Kahanic, Mohan Thakuri, Frederic Reu, Christopher M Reynolds, Rachael Sexton, Robert Z Orlowski, Bart Barlogie, Angela Dispenzieri
BACKGROUND: Lenalidomide plus dexamethasone is a reference treatment for patients with newly diagnosed myeloma. The combination of the proteasome inhibitor bortezomib with lenalidomide and dexamethasone has shown significant efficacy in the setting of newly diagnosed myeloma. We aimed to study whether the addition of bortezomib to lenalidomide and dexamethasone would improve progression-free survival and provide better response rates in patients with previously untreated multiple myeloma who were not planned for immediate autologous stem-cell transplant...
February 4, 2017: Lancet
B Lipe, R Vukas, J Mikhael
Multiple myeloma is the second most common type of blood cancer and remains incurable despite advances in therapy. Current therapy for multiple myeloma includes a phased-approach, often consisting of initial induction therapy, consolidation and maintenance therapy. With an ever-growing landscape of treatment options, the approach to optimal therapy has become increasingly complex. Specifically, controversy surrounds the optimal use and duration of maintenance therapy. We conducted a comprehensive literature search to analyze the most current literature and to provide recommendations for maintenance therapy in multiple myeloma...
October 21, 2016: Blood Cancer Journal
Evangelos Terpos, Martina Kleber, Monika Engelhardt, Sonja Zweegman, Francesca Gay, Efstathios Kastritis, Niels W C J van de Donk, Benedetto Bruno, Orhan Sezer, Annemiek Broijl, Sara Bringhen, Meral Beksac, Alessandra Larocca, Roman Hajek, Pellegrino Musto, Hans Erik Johnsen, Fortunato Morabito, Heinz Ludwig, Michele Cavo, Hermann Einsele, Pieter Sonneveld, Meletios A Dimopoulos, Antonio Palumbo
The European Myeloma Network provides recommendations for the management of the most common complications of multiple myeloma. Whole body low-dose computed tomography is more sensitive than conventional radiography in depicting osteolytic disease and thus we recommend it as the novel standard for the detection of lytic lesions in myeloma (grade 1A). Myeloma patients with adequate renal function and bone disease at diagnosis should be treated with zoledronic acid or pamidronate (grade 1A). Symptomatic patients without lytic lesions on conventional radiography can be treated with zoledronic acid (grade 1B), but its advantage is not clear for patients with no bone involvement on computed tomography or magnetic resonance imaging...
October 2015: Haematologica
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