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antibody multiple myeloma

Antonino Neri, Katia Todoerti, Marta Lionetti, Vittorio Simeon, Marzia Barbieri, Filomena Nozza, Gabriella Vona, Alessandra Pompa, Luca Baldini, Pellegrino Musto
Primary plasma cell leukemia (PPCL) is a rare and aggressive variant of multiple myeloma. The introduction of novel agents and modern technologies has recently partially changed the clinical and biological scenario of this malignancy, allowing limited, but not negligible, progresses. Areas covered: We will discuss the complex landscape of genetic alterations in PPCL, derived from conventional and high-throughput technologies; the best available treatments for PPCL; the possible future therapeutic perspectives...
October 19, 2016: Expert Review of Hematology
Muhammad Husnain, Sandra Kurtin, Nikki Barkett, Irbaz Bin Riaz, Amit Agarwal
Patients with relapsed and refractory multiple myeloma have poor prognosis. A recent analysis of patients with relapsed and refractory multiple myeloma who were refractory to both proteasome inhibitors and immunomodulatory drugs showed the median overall survival of 9 months only. Daratumumab is the first-in-class human monoclonal antibody against CD38 cells which was studied in phase I/II trials for treatment of these patients with relapsed refractory multiple myeloma. It showed an overall response rate of 36% and a median overall survival (OS) of 17 months in these patients...
2016: Case Reports in Oncological Medicine
Yogesh S Jethava, Frits van Rhee
Multiple myeloma is a disorder characterized by accumulation of malignant plasma cells in the bone marrow, hypercalcemia, monoclonal protein, and end organ damage. Recently newer generation proteosome inhibitors, monoclonal antibodies and novel agents have been approved by FDA, which is undoubtedly increasing life expectancy of the patients. However, hematopoietic stem cell transplantation still remains the cornerstone of the treatment. In this chapter, we are discussing the autologous stem cell transplant, allogeneic stem cell transplant and total therapy trials with outcomes...
2016: Cancer Treatment and Research
Susan J Lee, Ivan Borrello
Multiple myeloma (MM) is a hematologic cancer derived from malignant plasma cells within the bone marrow. Unlike most solid tumors, which originate from epithelial cells, the myeloma tumor is a plasma cell derived from the lymphoid cell lineage originating from a post-germinal B-cell. As such, the MM plasma cell represents an integral component of the immune system in terms of both antibody production and antigen presentation, albeit not efficiently. This fundamental difference has significant implications when one considers the implications of immunotherapy...
2016: Cancer Treatment and Research
Paola Neri, Nizar J Bahlis, Claudia Paba-Prada, Paul Richardson
Survival outcomes of patients with Multiple Myeloma (MM) have improved over the last decade due to the introduction of novel agents such as the immunomodulatory drugs thalidomide, lenalidomide (Len) and pomalidomide, and the proteasome inhibitors bortezomib (BTZ) and carfilzomib [1, 2]. However, despite these major advances, MM remains largely incurable and almost all patients relapse and require additional therapy [3]. The successful introduction of next generation novel agents including oral proteasome inhibitors, deacetylase inhibitors, and especially monoclonal antibodies as part of immunotherapy promises to further improve outcome...
2016: Cancer Treatment and Research
Jacob Laubach, Shaji Kumar
Treatment approaches for newly diagnosed myeloma have changed considerably during the past decade, along with a better understanding of the disease heterogeneity. Availability of new drug classes such as proteasome inhibitors and immunomodulatory drugs, and use of these drugs in combinations have led to higher response rates and deeper responses in the vast majority of patients with newly diagnosed myeloma. In addition to improved efficacy, these regimens are tolerated better than those with conventional chemotherapy drugs, which have reduced the early mortality seen in MM, while allowing for successful stem cell collection in patients undergoing stem cell transplant consolidation...
2016: Cancer Treatment and Research
Guillemette Fouquet, Francesca Gay, Eileen Boyle, Sara Bringhen, Alessandra Larocca, Thierry Facon, Xavier Leleu, Antonio Palumbo
Multiple myeloma (MM) is a disease of the elderly, with a median age at diagnosis of approximately 70 years old, and more than 30 % of patients aged >75 years. This latter and very elderly population is going to significantly rise in the near future given the increase in life expectancy in Western countries, and, most importantly, global health status of elderly patients is improving, justifying appropriate treatments. Changes in treatment paradigm from the old melphalan-prednisone regimen used since the 1970s to its use as a backbone in a nontransplant setting since the late 1990s have highlighted different subgroups in elderly MM...
2016: Cancer Treatment and Research
Bruno Paiva, Ramón García-Sanz, Jesús F San Miguel
Assessment of minimal residual disease (MRD) is becoming standard diagnostic care for potentially curable neoplasms such as some acute leukemias as well as chronic myeloid and lymphocytic leukemia. Although multiple myeloma (MM) remains as an incurable disease, around half of the patients achieve complete remission (CR), and recent data suggests increasing rates of curability with "total-therapy-like" programs. This landscape is likely to be improved with the advent of new antibodies and small molecules. Therefore, conventional serological and morphological techniques have become suboptimal for sensitive evaluation of highly effective treatment strategies...
2016: Cancer Treatment and Research
Hermann Einsele, Martin Schreder
Elotuzumab is a humanized monoclonal antibody targeting the extracellular domain of signaling lymphocytic activation molecule F7 (SLAMF7) highly expressed in multiple myeloma cells. Upon binding to myeloma cells, elotuzumab exerts its cytotoxic effects through antibody-dependent cellular cytotoxicity, the antibody-induced selective lysis of tumor cells by activated natural killer (NK) cells. Furthermore, elotuzumab has been shown to directly induce NK-cell activation by binding to SLAMF7 expressed on NK cells and to indirectly modulate T-cell function by promoting the secretion of cytokines from NK cells...
October 2016: Therapeutic Advances in Hematology
Peter M Voorhees, Saad Z Usmani
The advent of the immunomodulatory drugs thalido-mide, lenalidomide, and pomalidomide; the proteasome inhib-itors bortezomib, carfilzomib, and ixazomib; the histone deacet-ylase inhibitor panobinostat; and the monoclonal antibodies elotuzumab and daratumumab has led to dramatic improvements in outcomes for patients with multiple myeloma. Along with progress in nontransplant therapy have come questions regarding the continued role of high-dose melphalan (HDM) supported by autologous stem cell transplant (ASCT) in the treatment of multiple myeloma...
September 2016: Clinical Advances in Hematology & Oncology: H&O
Lisa A Raedler
No abstract text is available yet for this article.
March 2016: American Health & Drug Benefits
Lisa A Raedler
No abstract text is available yet for this article.
March 2016: American Health & Drug Benefits
C Wibmer, K Amrein, A Fahrleitner-Pammer, M M Gilg, A Berghold, G C Hutterer, W Maurer-Ertl, A Gerger, A Leithner, M Pichler, J Szkandera
Sclerostin has been proposed as a potent inhibitor of bone formation. Sclerostin antibodies are under clinical development to treat osteoporosis and metastatic bone disease. Serum sclerostin level is elevated in multiple myeloma, an osteolytic malignancy, where it might serve as predictive marker for the use of sclerostin-directed antibodies. As renal cell carcinoma (RCC) patients often present with osteolytic metastases, we aimed to investigate serum sclerostin levels in RCC patients. Our study included 53 RCC patients (19 with bone metastases, 25 with visceral metastases and 9 with localized disease) and 53 age- and gender-matched non-osteoporotic controls...
September 26, 2016: Scientific Reports
Kazunori Murata, Samuel I McCash, Brittany Carroll, Alexander M Lesokhin, Hani Hassoun, Nikoletta Lendvai, Neha S Korde, Sham Mailankody, Heather J Landau, Guenther Koehne, David J Chung, Sergio A Giralt, Lakshmi V Ramanathan, Ola Landgren
OBJECTIVES: To characterize the effect of three humanized IgG κ monoclonal antibodies (daratumumab, isatuximab, and elotuzumab) on the interpretation of results generated by protein electrophoresis, immunofixation, free light chain, and heavy/light chain assays performed on human serum. METHODS: Healthy volunteer serum and serum from multiple myeloma patients were supplemented with clinically relevant concentrations of each of the three monoclonal antibodies. These specimens then underwent analysis via serum protein electrophoresis, immunofixation, serum free light chain quantification, heavy/light chain quantification, total IgG, and total protein...
September 21, 2016: Clinical Biochemistry
Renate Burger, Andreas Guenther, Katja Klausz, Matthias Staudinger, Matthias Peipp, Eva Maria Murga Penas, Stefan Rose-John, John Wijdenes, Martin Gramatzki
Interleukin (IL)-6 has an important role in the pathophysiology of multiple myeloma where it supports the growth and survival of the malignant plasma cells in the bone marrow. It belongs to a family of cytokines which use the glycoprotein (gp)130 chain for signal transduction, such as oncostatin M or leukemia inhibitory factor (LIF). Targeting IL-6 in plasma cell diseases is currently evaluated in clinical trials with monoclonal antibodies (mAbs). Here, efforts were made to elucidate the contribution of IL-6 and gp130 signaling in malignant plasma cell growth in vivo...
September 22, 2016: Haematologica
Laurent Garderet, Gordon Cook, Holger W Auner, Benedetto Bruno, Henk Lokhorst, Jose Antonio Perez-Simon, Firoozeh Sahebi, Christof Scheid, Curly Morris, Anja van Biezen, Mohamad Sobh, Mauricette Michallet, Gösta Gahrton, Stefan Schönland, Nicolaus Kröger
Major improvements have been made in the treatment of myeloma. However, all patients, perhaps with some exceptions, eventually relapse, even after autologous stem cell transplantation (ASCT). In that setting, the combinations of new drugs, namely the IMiDs and the proteasome inhibitors along with steroids, give encouraging results in relapsed patients. The median progression-free survival (PFS) is 20 months with lenalidomide plus dexamethasone plus ixazomib and 26 months with lenalidomide plus dexamethasone plus carfilzomib...
September 21, 2016: Leukemia & Lymphoma
Maria Gavriatopoulou, Evangelos Terpos, Efstathios Kastritis, Meletios A Dimopoulos
INTRODUCTION: Renal impairment (RI) is one of the most common complication of multiple myeloma (MM). RI is present in almost 20% of MM patients at diagnosis and in 40%-50% of patients during the course of their disease. AREAS COVERED: Biology along with tools for diagnosis and management of RI are reported in this paper. Papers published in PubMed and reported abstracts up to May 2016 were used. EXPERT OPINION: Moderate and severe RI increases the risk of early death; thus rapid intervention and initiation of anti-myeloma treatment is essential and improves renal outcomes in RI patients...
September 27, 2016: Expert Opinion on Pharmacotherapy
M S Dal, A Doğan, A Karakuş, T Dal, M Kaya, O Ayyıldız
A 58-year-old female patient whose serological test results were Hepatitis B surface antigen (HBsAg) negative and Hepatitis B surface antibody (HBsAb) positive, diagnosed with Multiple myeloma. Autologous haematopoietic stem-cell transplantation was subsequently performed after induction chemotherapy. One-year later the patient was diagnosed as Hepatitis B Virus (HBV) reactivation and was started on lamivudine oral therapy. Hepatitis B surface antigen (HBsAg) negative is negative and HBsAb is positive in patients scheduled for chemotherapy, HBV DNA levels should still be investigated...
February 22, 2016: West Indian Medical Journal
Ensaf M Al-Hujaily, Robyn A A Oldham, Parameswaran Hari, Jeffrey A Medin
Multiple myeloma (MM) is a disorder of terminally differentiated plasma cells characterized by clonal expansion in the bone marrow (BM). It is the second-most common hematologic malignancy. Despite significant advances in therapeutic strategies, MM remains a predominantly incurable disease emphasizing the need for the development of new treatment regimens. Immunotherapy is a promising treatment modality to circumvent challenges in the management of MM. Many novel immunotherapy strategies, such as adoptive cell therapy and monoclonal antibodies, are currently under investigation in clinical trials, with some already demonstrating a positive impact on patient survival...
September 8, 2016: International Journal of Molecular Sciences
M Andrulis
The comprehensive sequencing of the complete genome of various hematological neoplasms has allowed an in-depth insight into the genomic heterogeneity and led to the discovery of new genetic aberrations, which seem to be very promising as therapeutic target structures. The molecular target structures of new therapeutic agents are, however, nearly exclusively proteins and cannot be directly identified with nucleic acid-based investigation methods. There is a great potential in investigations at the protein level that reflect an expression of the target protein and/or alterations of the signal cascade in tumor cells...
September 9, 2016: Der Pathologe
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