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https://www.readbyqxmd.com/read/29317395/the-role-of-elotuzumab-in-the-treatment-of-relapsed-or-refractory-multiple-myeloma
#1
REVIEW
Jill M Comeau, Katherine Kelly, Gary W Jean
PURPOSE: The pharmacology, pharmacokinetics, clinical efficacy and safety, cost, and place in therapy of elotuzumab for treatment of relapsed or refractory multiple myeloma (MM) are reviewed. SUMMARY: Elotuzumab is a humanized monoclonal antibody that targets the signaling lymphocytic activation molecule (SLAM) protein SLAMF7 and facilitates an antibody-dependent cellular cytotoxicity interaction between myeloma cells and natural killer cells. Elotuzumab has U.S...
January 15, 2018: American Journal of Health-system Pharmacy: AJHP
https://www.readbyqxmd.com/read/29315283/incorporating-monoclonal-antibodies-into-the-management-of-multiple-myeloma
#2
Tomer M Mark
No abstract text is available yet for this article.
December 2017: Clinical Advances in Hematology & Oncology: H&O
https://www.readbyqxmd.com/read/29305553/preclinical-efficacy-of-daratumumab-in-t-cell-acute-lymphoblastic-leukemia-t-all
#3
Karen L Bride, Tiffaney L Vincent, Soo-Yeon Im, Richard Aplenc, David M Barrett, William L Carroll, Robin Carson, Yunfeng Dai, Meenakshi Devidas, Kimberly P Dunsmore, Tori Fuller, Tina Glisovic-Aplenc, Terzah M Horton, Stephen P Hunger, Mignon L Loh, Shannon L Maude, Elizabeth A Raetz, Stuart S Winter, Stephan A Grupp, Michelle L Hermiston, Brent L Wood, David T Teachey
As a consequence of acquired or intrinsic disease resistance, the prognosis for patients with relapsed or refractory T-cell acute lymphoblastic leukemia (T-ALL) is dismal. Novel, less toxic drugs are clearly needed. One of the most promising emerging therapeutic strategies for cancer treatment is targeted immunotherapy. Immune therapies have improved outcomes for patients with other hematologic malignancies including B-ALL, however no immune therapy has been successfully developed for T-ALL. We hypothesize targeting CD38 will be effective against T-ALL...
January 5, 2018: Blood
https://www.readbyqxmd.com/read/29301755/copper-64-labeled-daratumumab-as-a-pet-ct-imaging-tracer-for-multiple-myeloma
#4
Enrico Caserta, Junie Chea, Megan Minnix, Domenico Viola, Steven Vonderfecht, Paul Yazaki, Desiree Crow, Jihane Khalife, James F Sanchez, Joycelynne M Palmer, Susanta Hui, Nadia Carlesso, Jonathan Keats, Young Kim, Ralf Buettner, Guido Marcucci, Steven Rosen, John Shively, David Colcher, Amrita Krishnan, Flavia Pichiorri
As a growing number of patients with multiple myeloma (MM) respond to upfront therapies while eventually relapsing in a time frame that is often non-predictable, attention has increasingly focused on developing novel diagnostic criteria to also account for disease dissemination. Positron emission tomography/computed tomography (PET/CT) is often used as a non-invasive monitoring strategy to assess cancer cell dissemination, but because the uptake of the currently used radiotracer 18fluoro-deoxyglucose (18F-FDG) is a function of the metabolic activity of both malignant and non-malignant cells, results frequently lack sufficient specificity...
January 4, 2018: Blood
https://www.readbyqxmd.com/read/29296961/network-meta-analysis-of-randomized-trials-in-multiple-myeloma-efficacy-and-safety-in-relapsed-refractory-patients
#5
Cirino Botta, Domenico Ciliberto, Marco Rossi, Nicoletta Staropoli, Maria Cucè, Teresa Galeano, Pierosandro Tagliaferri, Pierfrancesco Tassone
Despite major therapeutic advancements, multiple myeloma (MM) is still incurable and relapsed/refractory multiple myeloma (RRMM) remains a challenge; the rational choice of the most appropriate regimen in this setting is currently undefined. We performed a systematic review and 2 standard pairwise meta-analyses to evaluate the efficacy of regimens that have been directly compared with bortezomib or immunomodulatory imide drugs (IMiDs) in head-to-head clinical trials and a network meta-analysis (NMA) to determine the relevance of each regimen on the basis of all the available direct and indirect evidence...
February 28, 2017: Blood Advances
https://www.readbyqxmd.com/read/29296857/effects-of-daratumumab-on-natural-killer-cells-and-impact-on-clinical-outcomes-in-relapsed-or-refractory-multiple-myeloma
#6
Tineke Casneuf, Xu Steven Xu, Homer C Adams, Amy E Axel, Christopher Chiu, Imran Khan, Tahamtan Ahmadi, Xiaoyu Yan, Sagar Lonial, Torben Plesner, Henk M Lokhorst, Niels W C J van de Donk, Pamela L Clemens, A Kate Sasser
Daratumumab, a human CD38 imunoglobulin G 1κ monoclonal antibody, has demonstrated clinical activity and a manageable safety profile in monotherapy and combination therapy clinical trials in relapsed and/or refractory multiple myeloma. CD38 is expressed at high levels on myeloma cells and, to a lesser extent, on immune effector cells, including natural killer (NK) cells, which are important for daratumumab-mediated antibody-dependent cellular cytotoxicity (ADCC). Here, the pharmacodynamic effects of daratumumab monotherapy on NK cells, and the effect of NK cell dynamics on daratumumab efficacy and safety, were assessed...
October 24, 2017: Blood Advances
https://www.readbyqxmd.com/read/29296751/a-novel-cxcr4-antagonist-igg1-antibody-pf-06747143-for-the-treatment-of-hematologic-malignancies
#7
Shu-Hui Liu, Yin Gu, Bernadette Pascual, Zhengming Yan, Max Hallin, Cathy Zhang, Conglin Fan, Wenlian Wang, Justine Lam, Mary E Spilker, Rolla Yafawi, Eileen Blasi, Brett Simmons, Nanni Huser, Wei-Hsien Ho, Kevin Lindquist, Thomas-Toan Tran, Jyothirmayee Kudaravalli, Jing-Tyan Ma, Gretchen Jimenez, Ishita Barman, Colleen Brown, Sherman Michael Chin, Maria J Costa, David Shelton, Tod Smeal, Valeria R Fantin, Flavia Pernasetti
The chemokine receptor CXCR4 is highly expressed and associated with poor prognosis in multiple malignancies. Upon engagement by its ligand, CXCL12, CXCR4 triggers intracellular signaling pathways that control trafficking of cells to tissues where the ligand is expressed, such as the bone marrow (BM). In hematologic cancers, CXCR4-driven homing of malignant cells to the BM protective niche is a key mechanism driving disease and therapy resistance. We developed a humanized CXCR4 immunoglobulin G1 (IgG1) antibody (Ab), PF-06747143, which binds to CXCR4 and inhibits CXCL12-mediated signaling pathways, as well as cell migration...
June 27, 2017: Blood Advances
https://www.readbyqxmd.com/read/29296719/pd-1-blockade-enhances-elotuzumab-efficacy-in-mouse-tumor-models
#8
Natalie A Bezman, Amy Jhatakia, Alper Y Kearney, Ty Brender, Mark Maurer, Karla Henning, Misty R Jenkins, Amy J Rogers, Paul J Neeson, Alan J Korman, Michael D Robbins, Robert F Graziano
Elotuzumab, a humanized monoclonal antibody that binds human signaling lymphocytic activation molecule F7 (hSLAMF7) on myeloma cells, was developed to treat patients with multiple myeloma (MM). Elotuzumab has a dual mechanism of action that includes the direct activation of natural killer (NK) cells and the induction of NK cell-mediated antibody-dependent cellular cytotoxicity. This study aimed to characterize the effects of elotuzumab on NK cells in vitro and in patients with MM and to determine whether elotuzumab antitumor activity was improved by programmed death receptor-1 (PD-1) blockade...
May 9, 2017: Blood Advances
https://www.readbyqxmd.com/read/29284597/an-april-based-chimeric-antigen-receptor-for-dual-targeting-of-bcma-and-taci-in-multiple-myeloma
#9
Lydia Lee, Benjamin Draper, Neil Chaplin, Brian Philip, Melody Chin, Daria Galas-Filipowicz, Shimobi Onuoha, Simon Thomas, Vania Baldan, Reyisa Bughda, Paul Maciocia, Eva Kokalaki, Margarida P Neves, Dominic Patel, Manuel Rodriguez-Justo, James Francis, Kwee Yong, Martin Pule
B-cell maturation antigen (BCMA) is a promising therapeutic target for multiple myeloma (MM), but expression is variable, and early reports of BCMA targeting chimeric antigen receptors (CARs) suggest antigen down-regulation at relapse. Dual antigen targeting increases targetable tumour antigens and reduces the risk of antigen negative disease escape. 'A proliferation-inducing ligand' (APRIL) is a natural high affinity ligand for BCMA and transmembrane activator and CAML interactor (TACI). We quantified surface tumour expression of BCMA and TACI on primary MM cells (n=50)...
December 28, 2017: Blood
https://www.readbyqxmd.com/read/29282494/incidence-of-neutropenia-and-use-of-granulocyte-colony-stimulating-factors-in-multiple-myeloma-is-current-clinical-practice-adequate
#10
REVIEW
Xavier Leleu, Francesca Gay, Anne Flament, Kim Allcott, Michel Delforge
Although immunomodulatory drugs, alkylating agents, corticosteroids, protease inhibitors, and therapeutic monoclonal antibodies improve multiple myeloma outcomes, treatment burden is still an issue. Neutropenia is a known complication of cytotoxic cancer therapy and is often associated with infections; it is an important consideration in myeloma given the fact that patients often have a weakened immune system. The risk of febrile neutropenia increases with severe and persisting neutropenia. Recombinant granulocyte colony-stimulating factors (G-CSFs) are commonly used to reduce the incidence, duration, and severity of febrile neutropenia...
December 27, 2017: Annals of Hematology
https://www.readbyqxmd.com/read/29279102/a-question-of-class-treatment-options-for-patients-with-relapsed-and-or-refractory-multiple-myeloma
#11
REVIEW
Gordon Cook, Sonja Zweegman, María-Victoria Mateos, Florence Suzan, Philippe Moreau
Multiple classes of agent with distinct mechanisms of action are now available for the treatment of patients with relapsed and/or refractory multiple myeloma (RRMM), including immunomodulatory agents, proteasome inhibitors, histone deacetylase inhibitors and monoclonal antibodies. Additionally, several different drugs may be available within each agent class, each with their own specific efficacy and safety profile. This expansion of the treatment landscape has dramatically improved outcomes for patients. However, as the treatment options for RRMM become more complex, choosing the class of agent or combination of agents to use in the relapsed setting becomes increasingly challenging...
January 2018: Critical Reviews in Oncology/hematology
https://www.readbyqxmd.com/read/29250300/cultivation-and-immortalization-of-human-b-cells-producing-a-human-monoclonal-igm-antibody-binding-to-mda-ldl-further-evidence-for-formation-of-atherogenic-mda-ldl-adducts-in-humans-in-vivo
#12
Franz Tatzber, Edith Pursch, Ulrike Resch, Roswitha Pfragner, Sandra Holasek, Meinrad Lindschinger, Gerhard Cvirn, Willibald Wonisch
Oxidatively modified low-density lipoprotein (oLDL) is firmly believed to play an important role in the initiation and development of atherosclerosis, and malonic dialdehyde (MDA) is one of the major lipid peroxidation breakdown products involved in this process. In recent decades, antibodies against MDA-LDL have been detected in human and animal sera. In our study, human B-cells from the peripheral blood of a healthy female donor were fused with the SP2/0 mouse myeloma cell line. Antibody-producing hybridomas were detected by MDA-LDL-IgG/IgM enzyme-linked immunosorbent assays (ELISA) and Cu++-oxidized LDL IgG/IgM (oLAb) ELISA...
2017: Oxidative Medicine and Cellular Longevity
https://www.readbyqxmd.com/read/29244720/functional-imaging-with-18f-fdg-pet-ct-and-diffusion-weighted-imaging-dwi-in-early-response-evaluation-of-combination-therapy-of-elotuzumab-lenalidomide-and-dexamethasone-in-a-relapsed-multiple-myeloma-patient
#13
Christos Sachpekidis, Antonia Dimitrakopoulou-Strauss, Stefan Delorme, Hartmut Goldschmidt
Elotuzumab is the first monoclonal antibody approved for the treatment of relapsed-refractory multiple myeloma (MM) in combination with lenalidomide, an immunodulatory drug, and dexamethasone. We report on a multiply pre-treated MM patient with disease progression due to appearance of new focal lesions on imaging modalities, who was started on a combination treatment of elotuzumab, lenalidomide, and dexamethasone. After completion of three cycles of the new therapy the patient responded very well with a major decline of serological myeloma activity parameters serum monoclonal protein, kappa light chains, free light chains (FLC) ratio...
December 15, 2017: Diagnostics
https://www.readbyqxmd.com/read/29235380/pharmacokinetic-drug-evaluation-of-ixazomib-citrate-for-the-treatment-of-multiple-myeloma
#14
REVIEW
Marco Salvini, Rossella Troia, Davide Giudice, Chiara Pautasso, Mario Boccadoro, Alessandra Larocca
multiple myeloma (MM) is a plasma cell disorder that represents the second most frequent hematologic cancer. Although MM is still an incurable disease, prognosis has improved in the last decades thanks to the introduction of novel agents such as proteasome inhibitors (PIs), immunomodulatory drugs, monoclonal antibodies, and histone deacetylase inhibitors. Areas covered: ixazomib is the first oral PI recently approved by Food and Drug Administration (FDA) and European Medicine Agency (EMA) in combination with lenalidomide and dexamethasone as salvage therapy in MM patients...
January 2018: Expert Opinion on Drug Metabolism & Toxicology
https://www.readbyqxmd.com/read/29230672/the-role-of-b-cell-maturation-antigen-in-the-biology-and-management-of-and-as-a-potential-therapeutic-target-in-multiple-myeloma
#15
Eric Sanchez, Emily J Smith, Moryel A Yashar, Saurabh Patil, Mingjie Li, Autumn L Porter, Edward J Tanenbaum, Remy E Schlossberg, Camilia M Soof, Tara Hekmati, George Tang, Cathy S Wang, Haiming Chen, James R Berenson
B-cell maturation antigen (BCMA) was originally identified as a cell membrane receptor, expressed exclusively on late stage B-cells and plasma cells (PCs). Investigations of BCMA as a target for therapeutic intervention in multiple myeloma (MM) were initiated in 2007, using cSG1 as a naked antibody (Ab) as well as an Ab-drug conjugate (ADC) targeting BCMA, ultimately leading to ongoing clinical studies for previously treated MM patients. Since then, multiple companies have developed anti-BCMA-directed ADCs...
December 11, 2017: Targeted Oncology
https://www.readbyqxmd.com/read/29228209/cd38-knockout-suppresses-tumorigenesis-in-mice-and-clonogenic-growth-of-human-lung-cancer-cells
#16
Xiangning Bu, Jiro Kato, Julie A Hong, Maria J Merino, David S Schrump, Frances E Lund, Joel Moss
The ectodomain of the plasma membrane ecto-enzyme CD38 functions as both an NAD glycohydrolase and an ADP-ribosyl cyclase by catalyzing, respectively, the conversion of NAD to nicotinamide and ADP-ribose or cyclic ADP-ribose. CD38 is attracting particular attention in cancer therapy. An anti-CD38 monoclonal antibody (daratumumab) was approved for treatment of patients with multiple myeloma. However, the role of CD38 in non-hematological malignancies has not been explored. Previously, we reported that ADP-ribose-acceptor hydrolase (ARH)-1 deficiency in mice was associated with tumor development...
December 8, 2017: Carcinogenesis
https://www.readbyqxmd.com/read/29226427/case-report-treatment-of-light-chain-amyloidosis-with-daratumumab-monotherapy-in-two-patients
#17
Charlotte Gran, Gösta Gahrton, Evren Alici, Hareth Nahi
Immunoglobulin light-chain amyloidosis (AL) affects multiple organs, most prominently the kidney and the heart. Renal and cardiac impairment are both associated with poor prognosis.(1) Typical treatment regimens for AL include proteasome inhibitors, alkylating agents, and steroids as well as autologous stem cell transplantation (ASCT) for younger, fit patients. Complete response after treatment is associated with a better outcome and can be measured by free light chain (FLC) reduction.(2, 3) Monoclonal antibodies such as daratumumab (Dara, human IgG1 anti-CD38) have shown promising efficacy for the treatment of relapsed and refractory multiple myeloma...
December 11, 2017: European Journal of Haematology
https://www.readbyqxmd.com/read/29222300/emerging-options-in-multiple-myeloma-targeted-immune-and-epigenetic-therapies
#18
REVIEW
Shaji Kumar
Considerable progress has been made in the treatment of multiple myeloma in the past decade with median survival for the disease improving significantly. This has come through a combination of better understanding of the disease biology and coordinated research into new treatment approaches including better supportive care. However, patients eventually become refractory to available treatments and succumb to the disease, highlighting the need to develop new treatment approaches. The genetic heterogeneity in the disease and clonal evolution under treatment pressure underlie the development of resistance, underscoring the need to develop more effective therapies that can eradicate the disease at initial treatment as well as the need for new classes of drugs with varying mechanisms of action...
December 8, 2017: Hematology—the Education Program of the American Society of Hematology
https://www.readbyqxmd.com/read/29222299/management-of-multiple-myeloma-in-the-relapsed-refractory-patient
#19
REVIEW
Pieter Sonneveld
The approach to the patient with relapsed or relapsed/refractory multiple myeloma requires a careful evaluation of the results of previous treatments, the toxicities associated with it, and an assessment of prognostic factors. The majority of patients will have received prior therapy with drug combinations, including a proteasome inhibitor and an immune-modulatory agent. It is the physician's task to choose the right moment for the start of therapy and decide with the patient which goals need to be achieved...
December 8, 2017: Hematology—the Education Program of the American Society of Hematology
https://www.readbyqxmd.com/read/29222257/is-molecular-remission-the-goal-of-multiple-myeloma-therapy
#20
REVIEW
Faith E Davies
The increased number of effective therapies and the wider use of combinations that give deeper remissions have resulted in a reassessment of the goals of myeloma therapy. With the advent of new therapeutic strategies and diagnostic tools, achievement of minimal residual disease (MRD)-negative status has become increasingly important, with some even considering it as the primary endpoint for therapy. The level of MRD that is aimed for is a continuous, rather than an absolute variable, with studies in both transplant-eligible and -noneligible patients showing that the level of MRD achieved is predictive of progression-free survival and overall survival, with an improvement in survival of approximately 1 year for each log-depletion in MRD level...
December 8, 2017: Hematology—the Education Program of the American Society of Hematology
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