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antibody multiple myeloma

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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
#1
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
#2
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
#3
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) levels, an osteocyte-derived inhibitor of Wnt/β-catenin signaling, are elevated in MM patient sera and are 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
#4
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
#5
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
#6
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...
May 15, 2017: Expert Review of Hematology
https://www.readbyqxmd.com/read/28490215/the-safety-of-daratumumab-for-the-treatment-of-multiple-myeloma
#7
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
https://www.readbyqxmd.com/read/28490184/annals-express-electrophoretic-patterns-post-daratumumab
#8
Joanna Sheldon, Rachel D Wheeler, Ray Powles
BACKGROUND: Daratumumab (Darzalex) is a human IgG1 kappa monoclonal antibody targeting CD38 that has been recently approved for treatment of refractory multiple myeloma. As it is a monoclonal protein, it can be detected on routine serum protein electrophoresis and by immunofixation. METHODS: Sera from four patients were analysed by serum protein electrophoresis immediately pre- and post-treatment with Daratumumab. RESULTS: For all four patients, Daratumumab was visible on serum protein electrophoresis as an additional small band (approximately 1g/L) in the slow gamma region...
January 1, 2017: Annals of Clinical Biochemistry
https://www.readbyqxmd.com/read/28489849/utilizing-bmp-2-muteins-for-treatment-of-multiple-myeloma
#9
Axel Seher, Charlotte Lagler, Thorsten Stühmer, Urs Dietmar Achim Müller-Richter, Alexander Christian Kübler, Walter Sebald, Thomas Dieter Müller, Joachim Nickel
Multiple myeloma (MM) represents a haematological cancer characterized by the pathological hyper proliferation of antibody-producing B-lymphocytes. Patients typically suffer from kidney malfunction and skeletal disorders. In the context of MM, the transforming growth factor β (TGFβ) member Activin A was recently identified as a promoter of both accompanying symptoms. Because studies have shown that bone morphogenetic protein (BMP)-2-mediated activities are counteracted by Activin A, we analysed whether BMP2, which also binds to the Activin A receptors ActRII and ActRIIB but activates the alternative SMAD-1/5/8 pathway, can be used to antagonize Activin A activities, such as in the context of MM...
2017: PloS One
https://www.readbyqxmd.com/read/28483761/a-phase-1b-study-of-isatuximab-plus-lenalidomide-and-dexamethasone-for-relapsed-refractory-multiple-myeloma
#10
Thomas Martin, Rachid Baz, Don M Benson, Nikoletta Lendvai, Jeffrey Wolf, Pamela Munster, Alexander M Lesokhin, Claudine Wack, Eric Charpentier, Frank Campana, Ravi Vij
This phase 1b, open-label, dose-escalation study (NCT01749969) assessed the safety, efficacy, and pharmacokinetics of anti-CD38 monoclonal antibody isatuximab given in two schedules (3, 5, 10 mg/kg every other week [Q2W] or 10, 20 mg/kg weekly for 4 weeks then Q2W thereafter [QW/Q2W]), in combination with lenalidomide 25 mg (Days 1-21) and dexamethasone 40 mg (weekly), in patients with relapsed/refractory multiple myeloma (RRMM). Patients received 28-day treatment cycles; the primary objective was to determine the maximum tolerated dose (MTD) of isatuximab with lenalidomide and dexamethasone...
May 8, 2017: Blood
https://www.readbyqxmd.com/read/28474745/daratumumab-monotherapy-compared-with-historical-control-data-in-heavily-pretreated-and-highly-refractory-patients-with-multiple-myeloma-an-adjusted-treatment-comparison
#11
Saad Z Usmani, Joris Diels, Tetsuro Ito, Maneesha Mehra, Imran Khan, Annette Lam
Daratumumab is a human CD38-directed monoclonal antibody approved in the United States as monotherapy for patients with multiple myeloma (MM) who have received ≥3 prior lines of therapy (LOTs), including a proteasome inhibitor (PI) and an immunomodulatory agent (IMiD) or who are double refractory to a PI and an IMiD, and in combination with lenalidomide/dexamethasone or bortezomib/dexamethasone for patients with MM who have received ≥1 prior LOT. This study compared the efficacy of daratumumab monotherapy versus historical controls through adjusted treatment comparison...
May 5, 2017: American Journal of Hematology
https://www.readbyqxmd.com/read/28474469/how-do-i-work-up-pretransfusion-samples-containing-anti-cd38
#12
Waseem Q Anani, Kathleen Duffer, Richard M Kaufman, Gregory A Denomme
Anti-CD38 is used to treat relapsed or treatment-refractory multiple myeloma. CD38 monoclonal antibodies, however, can interfere with routine blood bank serologic tests. Agglutination is observed at the indirect phase of testing as the drug binds to red blood cells (RBCs). Resolving the testing interference causes delays issuing RBC units to patients with anemia. A number of devised methods to eliminate or bypass the effects of anti-CD38 on serologic tests are in use but no panacea exists. The limitations of each method require each testing site tailor an approach to best fit their needs...
May 5, 2017: Transfusion
https://www.readbyqxmd.com/read/28470777/cd38-negative-relapse-in-multiple-myeloma-after-daratumumab-based-chemotherapy
#13
Jiri Minarik, Martin Novak, Patrik Flodr, Jana Balcarkova, Miroslava Mlynarcikova, Petra Krhovska, Tomas Pika, Zuzana Pikalova, Jaroslav Bacovsky, Vlastimil Scudla
We present a case report of a patient relapsing after anti-CD38 treatment (daratumumab). The phenotype of the disease changed during this treatment and the myeloma clone became CD38 negative and daratumumab refractory. We expected clonal shift, however, based on immunophenotyping, cytogenetics and arrayCGH, the clone was identical as before daratumumab based treatment with the exception of CD38 negativity. We suggest that the downregulation or loss of CD38 might be an epigenetic "escape mechanism" of malignant plasma cells from antibody based treatment...
May 4, 2017: European Journal of Haematology
https://www.readbyqxmd.com/read/28468086/-comparison-and-analysis-of-minimal-residual-disease-in-multiple-myeloma-patients-detected-by-4-color-and-8-color-fluorescence-antibody-panels
#14
Y Z Wang, J Lu, L Hao, Y Chang, L L He, X J Huang, Y R Liu
Objective: To explore and compare 4-color and 8-color fluorescence antibody panels for detecting minimal residual disease of multiple myeloma patients after therapy. Methods: One 8-color antibody panel was built including CD38 and CD138 for the identification of plasma cells (PCs) , membrane antigen CD45, CD19, CD56 and CD117, cytoplasmic Kappa (cκ) and Lambda (cλ) light chain antigen. Six tubes of 4-color panels were built, among them, membrane antigen CD45/CD19, CD56/CD117, CD19/CD56 and light chains were analyzed combined by CD38/CD138 for PCs gate in the tubes M1-3 and tube C-(κ/λ), respectively; CD19 or CD45 and cκ/cλ light chains were detected in the tube MC1-(C)D38 for CD38/SSC identified PCs gate and tube MC2-(CD138) for CD138/SSC identified PCs gate separately...
April 14, 2017: Zhonghua Xue Ye Xue za Zhi, Zhonghua Xueyexue Zazhi
https://www.readbyqxmd.com/read/28462890/multiple-myeloma-clinical-updates-from-the-american-society-of-hematology-annual-meeting-2016
#15
REVIEW
Evangelos Terpos
The novel clinical data for plasma cell neoplasms (smoldering myeloma, multiple myeloma (MM) and AL-amyloidosis) that were presented in the 2016 Annual Meeting of the American Society of Hematology are summarized here. Data from large phase 3 studies for newly diagnosed MM patients who are eligible for autologous transplantation (EMN02, MRC XI and StaMINA trials) are described along with the results of phase 2 studies using novel anti-myeloma drug combinations for induction, consolidation and maintenance as first line therapy...
March 18, 2017: Clinical Lymphoma, Myeloma & Leukemia
https://www.readbyqxmd.com/read/28461396/pembrolizumab-pomalidomide-and-low-dose-dexamethasone-for-relapsed-refractory-multiple-myeloma
#16
Ashraf Badros, Elizabeth Hyjek, Ning Ma, Alexander Lesokhin, Ahmet Dogan, Aaron P Rapoport, Mehmet Kocoglu, Emily Lederer, Sunita Philip, Todd Milliron, Cameron Dell, Olga Goloubeva, Zeba Singh
Programmed death 1 (PD-1) receptor and its ligand (PD-L1) facilitate immune evasion in multiple myeloma (MM). We hypothesized that pembrolizumab, PD-1-antibody, can enhance anti-myeloma cellular immunity generated by pomalidomide leading to improved clinical responses. In this single-center, phase II study, 48 patients with relapsed/refractory MM (RRMM) received 28-days cycles of pembrolizumab, 200 mg intravenously every 2 weeks, pomalidomide 4 mg daily for 21 days and dexamethasone 40 mg weekly. Patients had a median of 3 (range: 2-5) lines of therapy, median age 64 (range: 35-83) years and had received both immune modulatory agent and proteasome inhibitor; (35 [73%] of 48) were refractory to both; (31 [70%]) had received an autologous transplant and (30 [62%]) had high-risk cytogenetics...
May 1, 2017: Blood
https://www.readbyqxmd.com/read/28454113/systematic-review-and-meta-analysis-of-the-efficacy-and-safety-of-novel-monoclonal-antibodies-for-treatment-of-relapsed-refractory-multiple-myeloma
#17
REVIEW
Tiantian Zhang, Sen Wang, Tengfei Lin, Jingmei Xie, Lina Zhao, Zhuoru Liang, Yangqiu Li, Jie Jiang
Although two newly launched monoclonal antibodies (mAbs), elotuzumab and daratumumab, performed well in patients with relapsed or relapsed/refractory multiple myeloma (RRMM), their efficacy and safety remain uncertain. We therefore performed a systematic review and meta-analysis of the most recent clinical trials that evaluated elotuzumab and/or daratumumab for the treatment of patients with RRMM. Our meta-analysis included 13 clinical trials with 2,402 patients participating. The overall response rate (ORR) was 57% (95% confidence interval [CI]: 38-76%), and the at least very good partial response rate (VGPR) was 32% (95% CI: 19-46%)...
May 16, 2017: Oncotarget
https://www.readbyqxmd.com/read/28450863/the-proteasome-inhibitor-bortezomib-controls-indoleamine-2-3-dioxygenase-1-breakdown-and-restores-immune-regulation-in-autoimmune-diabetes
#18
Giada Mondanelli, Elisa Albini, Maria T Pallotta, Claudia Volpi, Lucienne Chatenoud, Chantal Kuhn, Francesca Fallarino, Davide Matino, Maria L Belladonna, Roberta Bianchi, Carmine Vacca, Silvio Bicciato, Louis Boon, Giovanni Ricci, Ursula Grohmann, Paolo Puccetti, Ciriana Orabona
Bortezomib (BTZ) is a first-in-class proteasome inhibitor approved for the therapy of multiple myeloma that also displays unique regulatory activities on immune cells. The enzyme indoleamine 2,3-dioxygenase 1 (IDO1) is a tryptophan metabolizing enzyme exerting potent immunoregulatory effects when expressed in dendritic cells (DCs), the most potent antigen-presenting cells capable of promoting either immunity or tolerance. We previously demonstrated that, in inflammatory conditions, IDO1 is subjected to proteasomal degradation in DCs, turning these cells from immunoregulatory to immunostimulatory...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28448171/novel-investigational-drugs-active-as-single-agents-in-multiple-myeloma
#19
Mattia D'Agostino, Marco Salvini, Antonio Palumbo, Alessandra Larocca, Francesca Gay
Multiple myeloma (MM) is a hematologic malignancy characterized by proliferation of malignant plasma cells. patient outcome has improved markedly over the last decades due to the introduction of novel therapeutic agents such as bortezomib, thalidomide and lenalidomide. However, MM still remains largely incurable and patients eventually become refractory to available treatments. To address this unmet medical need, a variety of new molecules are currently being developed in preclinical models and/or are being investigated in clinical studies...
May 8, 2017: Expert Opinion on Investigational Drugs
https://www.readbyqxmd.com/read/28446321/-drug-resistant-mechanism-of-multiple-myeloma-and-its-therapy-combined-with-hdaci-review
#20
Liu-Fang Gu, Xiao-Guang Cui, Xing-Mei Cao, She-Ping Chen
Drug resistance of multiple myeloma(MM) has become more and more common, and greatly decreased the survival rate of these patients. The occurence of drug-resistance involves in many factors such as bone marrow microenveronment, tumor cell self-metabolism, cytokines, specific targets and so on. In this review, the potential mechanisms of resistance to glucocorticoid/proteasome inhibitor/immunomodulatory druges are briefly expounded in the aspect of tumor cell self-metabolism, including the changes of heat slock protein expression, mRNA expression, related cytokine levels and down-regulation of thalidomid-effecting site CRBN expression...
April 2017: Zhongguo Shi Yan Xue Ye Xue za Zhi
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