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antibody multiple myeloma

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https://www.readbyqxmd.com/read/28643017/safety-and-efficacy-of-daratumumab-in-japanese-patients-with-relapsed-or-refractory-multiple-myeloma-a-multicenter-phase-1-dose-escalation-study
#1
Shinsuke Iida, Kenshi Suzuki, Shigeru Kusumoto, Masaki Ri, Nobuhiro Tsukada, Yu Abe, Masayuki Aoki, Mitsuo Inagaki
Safety, efficacy, and pharmacokinetics (PK) of daratumumab as a monotherapy were investigated in Japanese patients with relapsed/refractory multiple myeloma (MM). This multicenter, dose-escalation study included patients (age ≥20 years) with ≥2 prior therapies. Daratumumab was administered intravenously: 8 mg/kg (n = 4) and 16 mg/kg (n = 5). The primary endpoint was safety. Secondary endpoints included objective response, overall response rate (ORR), progression-free survival (PFS), PK, and immunogenicity...
June 22, 2017: International Journal of Hematology
https://www.readbyqxmd.com/read/28633036/recent-advances-in-understanding-multiple-myeloma
#2
REVIEW
Parameswaran Hari
There have been major recent advancements in the understanding and management of multiple myeloma which in turn has led to unprecedented survival outcomes for patients. Diagnostic and response criteria have been recently revised. Our understanding of clonal progression, evolution, and clonal tides will inform therapeutic choices and appropriate treatment for patients. Response rates to initial induction with modern triplet therapies containing proteasome inhibitors and immunomodulators have made this approach the global standard for initial treatment...
June 13, 2017: Hematology/oncology and Stem Cell Therapy
https://www.readbyqxmd.com/read/28626216/therapeutic-effects-of-csf1r-blocking-antibodies-in-multiple-myeloma
#3
Q Wang, Y Lu, R Li, Y Jiang, Y Zheng, J Qian, E Bi, C Zhang, J Hou, S Wang, Q Yi
Our previous studies showed that macrophages (MФs), especially myeloma-associated MФs (MAMs) induce chemoresistance in human myeloma. Here we explored the potential of targeting MФs, by using colony-stimulating factor 1 receptor (CSF1R)-blocking mAbs, to treat myeloma. Our results showed that CSF1R blockade specifically inhibited the differentiation, proliferation and survival of murine M2 MФs and MAMs, and repolarized MAMs towards M1-like MФs in vitro. CSF1R blockade alone inhibited myeloma growth in vivo, by partially depleting MAMs, polarizing MAMs to the M1 phenotype, and inducing a tumor-specific cytotoxic CD4(+) T cell response...
June 19, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28622306/changes-in-uninvolved-immunoglobulins-during-induction-therapy-for-newly-diagnosed-multiple-myeloma
#4
P Ravi, S Kumar, W Gonsalves, F Buadi, M Q Lacy, R S Go, A Dispenzieri, P Kapoor, J A Lust, D Dingli, Y Lin, S J Russell, N Leung, M A Gertz, R A Kyle, P L Bergsagel, S V Rajkumar
Little is known about the impact of multiple myeloma (MM) treatment on uninvolved immunoglobulins (Ig). We identified 448 patients who received high-dose dexamethasone (HD-DEX), lenalidomide and dexamethasone (RD), bortezomib and dexamethasone (VD), bortezomib, cyclophosphamide and dexamethasone (VCD) or bortezomib, lenalidomide and dexamethasone (VRD) for newly diagnosed MM at our institution between 2000 and 2013, and who had available data on absolute lymphocyte count (ALC) and quantitative uninvolved Ig at baseline and at the end of four cycles of therapy...
June 16, 2017: Blood Cancer Journal
https://www.readbyqxmd.com/read/28615223/daratumumab-yields-rapid-and-deep-hematologic-responses-in-patients-with-heavily-pretreated-al-amyloidosis
#5
Gregory P Kaufman, Stanley L Schrier, Richard A Lafayette, Sally Arai, Ronald M Witteles, Michaela Liedtke
The majority of patients with immunoglobulin light chain amyloidosis (AL) fail to achieve a complete response (CR) to standard light chain suppressive chemotherapy, and almost all patients eventually experience hematologic relapse and progression of organ involvement; additional well tolerated treatment options are therefore needed. We present our retrospective experience of 25 consecutive previously treated AL patients who received daratumumab, a CD38-directed monoclonal antibody approved for the treatment of multiple myeloma...
June 14, 2017: Blood
https://www.readbyqxmd.com/read/28604269/elotuzumab-as-a-novel-anti-myeloma-immunotherapy
#6
Sabarinath Venniyil Radhakrishnan, Neelam Bhardwaj, Mary Steinbach, Janet Weidner, Tim Luetkens, Djordje Atanackovic
Treatment of multiple myeloma has undergone significant change in the last decade with the introduction of new immunomodulatory agents, proteasome inhibitors, and immunotherapeutic approaches. Elotuzumab is a humanized monoclonal antibody targeting CS1, which is a member of the SLAM (Signaling Lymphocyte Activation Molecule) family of proteins, expressed on the surface of myeloma plasma cells. Here we review the preclinical investigations that led to the development of elotuzumab and the clinical studies that resulted in its approval for the treatment of relapsed/refractory multiple myeloma...
June 12, 2017: Human Vaccines & Immunotherapeutics
https://www.readbyqxmd.com/read/28604120/current-and-developing-synthetic-pharmacotherapy-for-treating-relapsed-refractory-multiple-myeloma
#7
Klaus Podar, Martin Pecherstorfer
The introduction of novel agents has significantly improved multiple myeloma (MM) patient outcome during the last two decades. MM received the most drug approvals for any one malignancy during this time period, both in the United States as well as in Europe. Areas covered: Proteasome inhibitors, immunomodulatory drugs, and monoclonal antibodies are prototype drug classes, which target both specific MM cell functions, as well as the tumor supportive bone marrow microenvironment, and represent current cornerstones of MM therapy...
June 12, 2017: Expert Opinion on Pharmacotherapy
https://www.readbyqxmd.com/read/28601492/new-agents-in-multiple-myeloma-an%C3%A2-examination-of-safety-profiles
#8
REVIEW
Sara Bringhen, Edwin De Wit, Meletios-Athanassios Dimopoulos
Numerous treatments are available for relapsed and/or refractory multiple myeloma (MM), with safety profiles varying across drug classes and across agents within the same class. Thus, it is important to understand the toxicities of each antimyeloma agent when making treatment decisions. Neutropenia is commonly associated with lenalidomide and pomalidomide, and may be common with histone deacetylase (HDAC) inhibitors, but is relatively unusual with thalidomide, bortezomib, and carfilzomib. Infection was common in trials of lenalidomide and pomalidomide, and upper respiratory tract infection and pneumonia have been seen with carfilzomib...
May 10, 2017: Clinical Lymphoma, Myeloma & Leukemia
https://www.readbyqxmd.com/read/28592764/multiple-myeloma-pathophysiology-and-progress-in-management
#9
Junya Kuroda, Yoshiaki Chinen
There have been dramatic recent advances in understanding the basic pathophysiology and treatment strategies for multiple myeloma (MM). Research has shown both a high inter-patient diversity and intra-clonal heterogeneity even in a single patient in terms of cytogenetic/molecular abnormalities, and has also identified marked diversity in the immunological factors involved in tumor surveillance among MM patients. In the presence of a variety of novel agents, including molecular-targeted agents, immunomodulatory agents, and monoclonal antibodies, the optimal translation of current knowledge on both molecular and immunologic findings into clinical use is crucial for managing MM...
2017: [Rinshō Ketsueki] the Japanese Journal of Clinical Hematology
https://www.readbyqxmd.com/read/28575847/expression-of-cd38-in-myeloma-bone-niche-a-rational-basis-for-the-use-of-anti-cd38-immunotherapy-to-inhibit-osteoclast-formation
#10
Federica Costa, Denise Toscani, Antonella Chillemi, Valeria Quarona, Marina Bolzoni, Valentina Marchica, Rosanna Vescovini, Cristina Mancini, Eugenia Martella, Nicoletta Campanini, Chiara Schifano, Sabrina Bonomini, Fabrizio Accardi, Alberto L Horenstein, Franco Aversa, Fabio Malavasi, Nicola Giuliani
It is known that multiple myeloma (MM) cells express CD38 and that a recently developed human anti-CD38 monoclonal antibody Daratumumab mediates myeloma killing. However, the expression of CD38 and other functionally related ectoenzymes within the MM bone niche and the potential effects of Daratumumab on bone cells are still unknown. This study firstly defines by flow cytometry and immunohistochemistry the expression of CD38 by bone marrow cells in a cohort of patients with MM and indolent monoclonal gammopathies...
May 16, 2017: Oncotarget
https://www.readbyqxmd.com/read/28573863/cd38-as-a-pet-imaging-target-in-lung-cancer
#11
Emily B Ehlerding, Christopher G England, Dawei Jiang, Stephen A Graves, Lei Kang, Saige Lacognata, Todd E Barnhart, Weibo Cai
Daratumumab (Darzalex, Janssen Biotech) is a clinically approved antibody targeting CD38 for the treatment of multiple myeloma. However, CD38 is also expressed by other cancer cell types, including lung cancer, where its expression or absence may offer prognostic value. We therefore developed a PET tracer based upon daratumumab for tracking CD38 expression, utilizing murine models of non-small cell lung cancer to verify its specificity. Daratumumab was prepared for radiolabeling with (89)Zr (t1/2 = 78.4 h) through conjugation with desferrioxamine (Df)...
June 8, 2017: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/28561703/hematologic-malignancies-plasma-cell-disorders
#12
Madhav V Dhodapkar, Ivan Borrello, Adam D Cohen, Edward A Stadtmauer
Multiple myeloma (MM) is a plasma cell malignancy characterized by the growth of tumor cells in the bone marrow. Properties of the tumor microenvironment provide both potential tumor-promoting and tumor-restricting properties. Targeting underlying immune triggers for evolution of tumors as well as direct attack of malignant plasma cells is an emerging focus of therapy for MM. The monoclonal antibodies daratumumab and elotuzumab, which target the plasma cell surface proteins CD38 and SLAMF7/CS1, respectively, particularly when used in combination with immunomodulatory agents and proteasome inhibitors, have resulted in high response rates and improved survival for patients with relapsed and refractory MM...
2017: American Society of Clinical Oncology Educational Book
https://www.readbyqxmd.com/read/28556890/recent-progress-in-relapsed-multiple-myeloma-therapy-implications-for-treatment-decisions
#13
REVIEW
Philippe Moreau, Edwin de Wit
The availability of novel therapies for the treatment of multiple myeloma has had a dramatic impact on the depth of response that can be expected on initial treatment. Despite these advances, disease relapse remains inevitable in most patients and brings with it a different set of priorities for therapy. The most recent wave of novel agents may have a particular impact in the relapsed setting. In this review, we examine the evidence currently available from clinical trials for the use of novel agents, particularly in the formation of triplet therapy...
May 30, 2017: British Journal of Haematology
https://www.readbyqxmd.com/read/28544116/incidence-characteristics-and-outcome-of-solitary-plasmacytoma-and-plasma-cell-leukemia-population-based-data-from-the-swedish-myeloma-register
#14
Hareth Nahi, Anna Genell, Göran Wålinder, Katarina Uttervall, Gunnar Juliusson, Karin Forsberg, Markus Hansson, Ronald Svensson, Olle Linder, Kristina Carlson, Bo Björkstrand, Sigurdur Y Kristinsson, Ulf Henrik Mellqvist, Cecilie Blimark, Ingemar Turesson
Solitary plasmacytoma (SP) and Plasma cell leukemia (PCL) are uncommon (3-6%) types of plasma cell disease. The risk of progression to symptomatic multiple myeloma (MM) is probably important for the outcome of SP. PCL is rare and has a dismal outcome. In this study we report on incidence and survival in PCL/SP, and progression to MM in SP, using the prospective observational Swedish Multiple Myeloma Register designed to document all newly diagnosed plasma cell diseases in Sweden since 2008. Both solitary bone plasmacytoma (SBP), (n=124) and extramedullary plasmacytoma (EMP), (n=67) have better overall survival (OS) than MM (n=3549)...
May 22, 2017: European Journal of Haematology
https://www.readbyqxmd.com/read/28540859/case-report-serological-testing-interference-of-daratumumab-anti-cd38-therapy-in-multiple-myeloma
#15
Élodie Rabut, Annabelle Castro-Fernandez, Virginie Le Gall, Nihad Meknache
We report the case of a 54 years old patient monitored for a monoclonal IgG kappa light chain refractory relapsed multiple myeloma and receiving daratumumab immunotherapy. Daratumumab (DARA), a monoclonal anti-CD38 antibody, belongs to the new generation of immunotherapy in refractory relapse multiple myeloma which the medical pathologist should be aware of to avoid misinterpretation of biological tests performed for patients followed for this disease. By its IgG1K humanized monoclonal antibody backbone, DARA interferes in both serum protein electrophoresis and immunofixation by the presence of an alternate IgGK monoclonal peak, leading to a possible difficulty to assess treatment's response in monoclonal IgG kappa light chain myeloma...
June 1, 2017: Annales de Biologie Clinique
https://www.readbyqxmd.com/read/28529307/genetic-deletion-of-sost-or-pharmacological-inhibition-of-sclerostin-prevent-multiple-myeloma-induced-bone-disease-without-affecting-tumor-growth
#16
J Delgado-Calle, J Anderson, M D Cregor, K W Condon, S A Kuhstoss, L I Plotkin, T Bellido, G D Roodman
Multiple myeloma (MM) causes lytic bone lesions due to increased bone resorption and concomitant marked suppression of bone formation. Sclerostin (Scl), an osteocyte-derived inhibitor of Wnt/β-catenin signaling, is elevated in MM patient sera and increased in osteocytes in MM-bearing mice. We show here that genetic deletion of Sost, the gene encoding Scl, prevented MM-induced bone disease in an immune-deficient mouse model of early MM, and that administration of anti-Scl antibody (Scl-Ab) increased bone mass and decreases osteolysis in immune-competent mice with established MM...
May 22, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28515094/inhibiting-the-osteocyte-specific-protein-sclerostin-increases-bone-mass-and-fracture-resistance-in-multiple-myeloma
#17
Michelle M McDonald, Michaela R Reagan, Scott E Youlten, Sindhu T Mohanty, Anja Seckinger, Rachael L Terry, Jessica A Pettitt, Marija K Simic, Tegan L Cheng, Alyson Morse, Lawrence M T Le, David Abi-Hanna, Ina Kramer, Carolyne Falank, Heather Fairfield, Irene M Ghobrial, Paul A Baldock, David G Little, Michaela Kneissel, Karin Vanderkerken, J H Duncan Bassett, Graham R Williams, Babatunde O Oyajobi, Dirk Hose, Tri G Phan, Peter I Croucher
Multiple myeloma is a plasma cell cancer that develops in the skeleton causing profound bone destruction and fractures. The bone disease is mediated by increased osteoclastic bone resorption and suppressed bone formation. Treatment with bisphosphonates, which inhibit bone resorption, prevents bone loss but fail to influence bone formation and do not replace lost bone, so patients continue to fracture. Stimulating bone formation to increase bone mass and fracture resistance is a priority; however, targeting tumor-derived modulators of bone formation has had limited success...
May 17, 2017: Blood
https://www.readbyqxmd.com/read/28506593/a-rational-strategy-for-reducing-on-target-off-tumor-effects-of-cd38-chimeric-antigen-receptors-by-affinity-optimization
#18
Esther Drent, Maria Themeli, Renée Poels, Regina de Jong-Korlaar, Huipin Yuan, Joost de Bruijn, Anton C M Martens, Sonja Zweegman, Niels W C J van de Donk, Richard W J Groen, Henk M Lokhorst, Tuna Mutis
Chimeric antigen receptors (CARs) can effectively redirect cytotoxic T cells toward highly expressed surface antigens on tumor cells. The low expression of several tumor-associated antigens (TAAs) on normal tissues, however, hinders their safe targeting by CAR T cells due to on-target/off-tumor effects. Using the multiple myeloma (MM)-associated CD38 antigen as a model system, here, we present a rational approach for effective and tumor-selective targeting of such TAAs. Using "light-chain exchange" technology, we combined the heavy chains of two high-affinity CD38 antibodies with 176 germline light chains and generated ∼124 new antibodies with 10- to >1,000-fold lower affinities to CD38...
May 13, 2017: Molecular Therapy: the Journal of the American Society of Gene Therapy
https://www.readbyqxmd.com/read/28504554/how-is-patient-care-for-multiple-myeloma-advancing
#19
REVIEW
Sonja Genadieva Stavric, Francesca Bonello, Sara Bringhen, Mario Boccadoro, Alessandra Larocca
Treatment of multiple myeloma has undergone profound changes in the past years thanks to the increased understanding of the biology of the disease and the new treatment options. New drugs and effective approaches are currently available for the treatment of multiple myeloma, including immunomodulatory agents, proteasome inhibitors and autologous stem cell transplantation. Areas covered: We have described the recent updated criteria to start treatment in multiple myeloma and summarized clinical data from major studies including most recent agents...
June 2017: Expert Review of Hematology
https://www.readbyqxmd.com/read/28490215/the-safety-of-daratumumab-for-the-treatment-of-multiple-myeloma
#20
REVIEW
María J Cejalvo, Paz Ribas, Javier de la Rubia
The overall survival of patients with multiple myeloma (MM) has changed dramatically in the last decade. MM remains an incurable plasma cell disorder but immunotherapy with monoclonal antibodies (MoAbs) has emerged as a promising treatment. Areas covered: Fully published, clinical trials including patients with relapsed or refractory MM were reviewed. Safety data of daratumumab (DARA) single-agent or in combination regimens have been addressed. Additionally, infusion-related reactions, data on special populations, and DARA-interference with laboratory testing, including assessment of MM response in patients have also been addressed...
June 2017: Expert Opinion on Drug Safety
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