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https://www.readbyqxmd.com/read/29127588/daratumumab-a-review-in-relapsed-and-or-refractory-multiple-myeloma
#1
Hannah A Blair
Intravenous daratumumab (DARZALEX(®)) is a first-in-class human IgG1κ monoclonal antibody against CD38 available for use in patients with relapsed and/or refractory multiple myeloma. In phase I/II and II trials and a pooled analysis of these studies, daratumumab monotherapy induced an overall response (partial response or better) in approximately one-third of patients; responses were rapid, deep and durable. An overall survival (OS) benefit was seen with daratumumab monotherapy, including in patients with a minimal response or stable disease...
November 10, 2017: Drugs
https://www.readbyqxmd.com/read/29118010/cd38-antibodies-in-multiple-myeloma-back-to-the-future
#2
Niels W C J van de Donk, Paul G Richardson, Fabio Malavasi
CD38 is highly and uniformly expressed on MM cells, and at relatively low levels on normal lymphoid and myeloid cells, and in some tissues of non-hematopoietic origin. CD38 is a transmembrane glycoprotein with ectoenzymatic activity, and also functions as receptor and adhesion molecule. Altogether, this has triggered the development of several CD38 antibodies including daratumumab (fully human), isatuximab (chimeric), and MOR202 (fully human). CD38 antibodies have pleiotropic mechanisms of action including Fc-dependent immune effector mechanisms, direct apoptotic activity, and immunomodulatory effects by the elimination of CD38-positive immunesuppressor cells...
November 8, 2017: Blood
https://www.readbyqxmd.com/read/29098319/-multiple-myeloma-what-has-been-confirmed-in-therapy
#3
REVIEW
M-A Baertsch, H Goldschmidt
Multiple myeloma (MM) is a malignancy of terminally differentiated B cells/plasma cells and is primarily located in the bone marrow. Symptomatic multiple myeloma typically presents with osteolyses, anemia, reduced renal function, and/or hypercalcemia. In the case of such MM-related end organ damage, urgent systemic treatment is indicated. In order to prevent end organ damage, current guidelines now recommend treatment initiation already when certain biomarkers are met. Current first-line treatment is based on proteasome inhibition and immunomodulation...
November 2, 2017: Der Internist
https://www.readbyqxmd.com/read/29079129/double-cd38-cd138-negative-multiple-myeloma
#4
Vitaliy Mykytiv, Abrar Alwaheed, Nurul Asyikin Mohd Hashim
The standard diagnosis of multiple myeloma by flow cytometry is based on selection of population of CD38(+)/CD138(+) positives cells. As the result treatment with proteasome inhibitors, CD138 may be underexpressed on atypical plasma cells. Thus, in order to improve this strategy, recently new CD138-independent method, based on CD38 positivity of plasma cells was developed. We present an unusual case of CD138(-) negative multiple myeloma which had become double CD138(-)/CD38(-) negative after treatment with daratumumab by which we would like to illustrate potential pitfalls of both strategies...
October 18, 2017: Hematology/oncology and Stem Cell Therapy
https://www.readbyqxmd.com/read/29064593/combination-therapy-incorporating-bcl-2-inhibition-with-venetoclax-for-the-treatment-of-refractory-primary-plasma-cell-leukemia-with-t-11-14
#5
Wilson I Gonsalves, Francis K Buadi, Shaji K Kumar
Primary plasma cell leukemia (pPCL) is the most aggressive form of the plasma cell (PC) malignancy, multiple myeloma (MM). It has been commonly associated with the presence of a chromosome translocation involving the immunoglobulin heavy chain (IgH) locus on 14q32, i.e. t (11;14). Results from early phase clinical trials utilizing the selective bcl-2 inhibitor, venetoclax, as a single agent in patients with relapsed MM have had remarkable efficacy among patients with t (11;14) abnormality. The present case demonstrates the ability of a combination regimen incorporating bcl-2 inhibition with daratumumab, bortezomib, venetoclax and dexamethasone to induce a rapid and very deep hematologic response in a pPCL patient with t (11;14), even in a setting of very refractory disease...
October 24, 2017: European Journal of Haematology
https://www.readbyqxmd.com/read/29054515/blood-transfusion-management-and-transfusion-related-outcomes-in-daratumumab-treated-patients-with-relapsed-or-refractory-multiple-myeloma
#6
Ajai Chari, Suzanne Arinsburg, Sundar Jagannath, Toshihisa Satta, Ivey Treadwell, Donna Catamero, Gillian Morgan, Huaibao Feng, Clarissa Uhlar, Imran Khan, Parul Doshi, Saad Usmani
INTRODUCTION: Daratumumab, a human CD38 monoclonal antibody approved for multiple myeloma (MM) treatment, binds red blood cells (RBCs), resulting in panagglutination in compatibility tests. Published mitigation methods avoid additional testing, ensuring timely release of blood products. Blood transfusion management and transfusion-related outcomes of daratumumab-treated patients in the SIRIUS study are reported, with emphasis on 2 clinical sites. PATIENTS AND METHODS: Patients had MM treated with ≥ 3 prior lines of therapy, including a proteasome inhibitor and an immunomodulatory drug, or were refractory to a proteasome inhibitor and an immunomodulatory drug...
September 19, 2017: Clinical Lymphoma, Myeloma & Leukemia
https://www.readbyqxmd.com/read/29043827/stability-guidelines-for-dithiothreitol-treated-red-blood-cell-reagents-used-for-antibody-detection-methods-in-patients-treated-with-daratumumab
#7
Wendy L Disbro
Daratumumab (DARA), a drug used to treat patients with multiple myeloma, causes interference in pre-transfusion testing. Samples from patients receiving DARA exhibit panreactivity in antibody detection and identification tests with red blood cells (RBCs). Many hospitals are sending these samples to reference laboratories. Dithiothreitol (DTT), a sulfhydryl chemical treatment of RBCs, negates this reactivity. This study investigated the stability of the antigens on DTT-treated RBCs to determine if large quantities of RBCs could be treated at one time, stored, and used for testing at a later time...
September 2017: Immunohematology
https://www.readbyqxmd.com/read/29025987/preclinical-development-of-cd38-targeted-89-zr-zr-dfo-daratumumab-for-imaging-multiple-myeloma
#8
Anchal Ghai, Dolonchampa Maji, Nicholas Cho, Chantiya Chanswangphuwana, Michael Rettig, John DiPersio, Walter Akers, Farrokh Dehdashti, Samuel Achilefu, Ravi Vij, Monica Shokeen
Multiple myeloma (MM) is a plasma B-cell hematologic cancer that causes significant skeletal morbidity. Despite improvements in survival, heterogeneity in response remains a major challenge in MM. Cluster of differentiation 38 (CD38) is a type II transmembrane glycoprotein over-expressed in myeloma cells and is implicated in MM cell signaling. Daratumumab is US Food and Drug Administration approved high-affinity monoclonal antibody targeting CD38 that is clinically benefiting refractory MM patients. Here, we evaluated [(89)Zr]Zr-DFO-daratumumab positron emission tomography/computed tomography (PET/CT) imaging in MM tumor models...
October 12, 2017: Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine
https://www.readbyqxmd.com/read/29025767/monocytes-and-granulocytes-reduce-cd38-expression-levels-on-myeloma-cells-in-patients-treated-with-daratumumab
#9
Jakub Krejcik, Kristine A Frerichs, Inger S Nijhof, Berris van Kessel, Jeroen van Velzen, Andries C Bloem, Marloes Broekmans, Sonja Zweegman, Johan van Meerloo, René J Musters, Pino Poddighe, Richard Groen, Christopher Chiu, Torben Plesner, Henk M Lokhorst, A Kate Sasser, Tuna Mutis, Niels W C J van de Donk
PURPOSE: Daratumumab treatment results in a marked reduction of CD38 expression on multiple myeloma (MM) cells. The aim of this study was to investigate the clinical implications and the underlying mechanisms of daratumumab-mediated CD38 reduction. EXPERIMENTAL DESIGN: We evaluated the effect of daratumumab alone or in combination with lenalidomide-dexamethasone, on CD38 levels of MM cells and non-tumor immune cells in the GEN501 study (daratumumab monotherapy) and the GEN503 study (daratumumab combined with lenalidomide-dexamethasone)...
October 12, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28983805/influence-of-disease-and-patient-characteristics-on-daratumumab-exposure-and-clinical-outcomes-in-relapsed-or-refractory-multiple-myeloma
#10
Xiaoyu Yan, Pamela L Clemens, Thomas Puchalski, Sagar Lonial, Henk Lokhorst, Peter M Voorhees, Saad Usmani, Paul G Richardson, Torben Plesner, Kevin Liu, Robert Z Orlowski, Nedjad Losic, Richard Jansson, Tahamtan Ahmadi, Kristen Lantz, Juan Jose Perez Ruixo, Honghui Zhou, Xu Steven Xu
OBJECTIVE: The aim of this study was to understand the influence of disease and patient characteristics on exposure to daratumumab, an immunoglobulin Gκ (IgGκ) monoclonal antibody, and clinical outcomes in relapsed or refractory multiple myeloma (MM). PATIENTS AND METHODS: Baseline myeloma type, albumin levels, renal/hepatic function, age, sex, race, weight, Eastern Cooperative Oncology Group (ECOG) status, refractory status, and number of prior therapies were evaluated using data from two clinical studies-GEN501 (N = 104) and SIRIUS (N = 124)...
October 5, 2017: Clinical Pharmacokinetics
https://www.readbyqxmd.com/read/28978849/therapeutic-approach-for-relapsed-refractory-multiple-myeloma-the-logic-and-practice
#11
Junya Kuroda
The long-term outcome of multiple myeloma (MM) has been greatly improved by the advent of new agents such as proteasome inhibitors (PIs) and immunomodulatory drugs (IMiDs), despite the disease remaining mostly incurable. Treatment design is the critical determinant for the survival period and for the quality and way of life in patients with relapsed/refractory MM (RRMM). Recently, the choice of therapeutic options for RRMM has been expanded by the introduction of second generation PIs such as carfilzomib and ixazomib, and therapeutic monoclonal antibodies such as elotuzumab and daratumumab...
2017: [Rinshō Ketsueki] the Japanese Journal of Clinical Hematology
https://www.readbyqxmd.com/read/28970695/interference-of-daratumumab-with-pretransfusion-testing-mimicking-a-high-titer-low-avidity-like-antibody
#12
Mei-Hwa Lin, Fei-Yun Liu, Hsiu-Mien Wang, Hsin-Ching Cho, Shyh-Chyi Lo
Daratumumab is a monoclonal immunoglobulin against CD38 and has been approved for treating patients with refractory multiple myeloma. The presence of daratumumab in the sera can interfere with pretransfusion testing due to the weakly expression of CD38 on red cells. The reactivity could be mistaken as autoantibody (if autocontrol is positive) or alloantibody (if autocontrol is negative). We present a case that demonstrates daratumumab could mimic a high titer low avidity (HTLA) alloantibody. A 34-year-old male patient of refractory myeloma was recruited in phase three clinical trial involving daratumumab...
July 2017: Asian Journal of Transfusion Science
https://www.readbyqxmd.com/read/28967482/cost-effectiveness-of-pomalidomide-carfilzomib-and-daratumumab-for-the-treatment-of-patients-with-heavily-pretreated-relapsed-refractory-multiple-myeloma-in-the-united-states
#13
Christopher G Pelligra, Kejal Parikh, Shien Guo, Conor Chandler, Jorge Mouro, Safiya Abouzaid, Sikander Ailawadhi
PURPOSE: Pomalidomide plus low-dose dexamethasone (POM-d), daratumumab monotherapy (DARA), and carfilzomib monotherapy (CAR) have been approved for use in the treatment of patients with heavily pretreated relapsed-refractory multiple myeloma (RRMM) in the US, based on findings from the MM-002, SIRIUS, and PX-171-003-A1 studies, respectively. The objective of this study was to assess the cost-effectiveness of POM-d, DARA, and CAR in this patient population from a US payer's perspective...
September 26, 2017: Clinical Therapeutics
https://www.readbyqxmd.com/read/28915615/expression-of-cd38-in-myeloma-bone-niche-a-rational-basis-for-the-use-of-anti-cd38-immunotherapy-to-inhibit-osteoclast-formation
#14
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...
August 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28904172/fda-approval-summary-daratumumab-for-treatment-of-multiple-myeloma-after-one-prior-therapy
#15
Vishal Bhatnagar, Nicole J Gormley, Lola Luo, Yuan Li Shen, Rajeshwari Sridhara, Sriram Subramaniam, Guoxiang Shen, Lian Ma, Stacy Shord, Kirsten B Goldberg, Ann T Farrell, Amy E McKee, Richard Pazdur
On November 21, 2016, the U.S. Food and Drug Administration granted regular approval to daratumumab in combination with lenalidomide and dexamethasone, or bortezomib and dexamethasone, for the treatment of patients with multiple myeloma who have received at least one prior therapy. Approval was based on two randomized, open-label trials in which daratumumab was added to these backbone therapies. The MMY3003 trial demonstrated substantial improvement in progression-free survival (PFS) when daratumumab was added to lenalidomide and dexamethasone compared with lenalidomide and dexamethasone alone...
September 13, 2017: Oncologist
https://www.readbyqxmd.com/read/28883263/combination-therapy-with-monoclonal-antibodies-for-treatment-of-newly-diagnosed-multiple-myeloma
#16
Noriko Nishimura, Yasuhito Terui, Kiyohiko Hatake
Monoclonal antibodies (mAbs) with new mechanisms of action are emerging as promising agents for patients with multiple myeloma (MM). Of these, anti-CD38 antibodies and anti-signaling lymphocytic activation molecule F7 (SLAMF7) antibody have demonstrated efficacy for relapsed and refractory myeloma (RRMM). Two CD38-targeting antibodies, daratumumab and isatuximab had significant activity as single agents, whereas the SLAMF7-targeting antibody, elotuzumab, did not. Patients with RRMM treated with 16 mg/kg daratumumab achieved at least PR of 36% and 29% in two distinct phase 2 studies...
2017: [Rinshō Ketsueki] the Japanese Journal of Clinical Hematology
https://www.readbyqxmd.com/read/28857616/adoptive-cell-therapy-in-multiple-myeloma
#17
Sonia Vallet, Martin Pecherstorfer, Klaus Podar
Recent breakthrough advances in Multiple Myeloma (MM) immunotherapy have been achieved with the approval of the first two monoclonal antibodies, elotuzumab and daratumumab. Adoptive cell therapy (ACT) represents yet another, maybe the most powerful modality of immunotherapy, in which allogeneic or autologous effector cells are expanded and activated ex vivo followed by their re-infusion back into patients. Infused effector cells belong to two categories: naturally occurring, non-engineered cells (donor lymphocyte infusion, myeloma infiltrating lymphocytes, deltagamma T cells) or genetically- engineered antigen-specific cells (chimeric antigen receptor T or NK cells, TCR-engineered cells)...
September 6, 2017: Expert Opinion on Biological Therapy
https://www.readbyqxmd.com/read/28840598/therapeutic-monoclonal-antibodies-in-combination-with-pomalidomide-can-overcome-refractoriness-to-both-agents-in-multiple-myeloma-a-case-based-approach
#18
Marc-Andrea Baertsch, Michael Hundemer, Jens Hillengass, Hartmut Goldschmidt, Marc S Raab
In multiple myeloma (MM), the synergy between immunomodulatory drugs (IMiDs) and monoclonal antibodies (MABs) has been demonstrated in several pivotal trials. However, disease refractory to either class of compounds remains a major therapeutic challenge. We here report on 3 heavily pretreated MM patients who were refractory to pomalidomide as well as to MABs against CD38 (daratumumab) or CD20 (rituximab), respectively, but who responded to retreatment with the same agents in combination. Responses were durable with PFS of 7, 10 (ongoing), and 30 months from initiation of combination treatment...
August 25, 2017: Hematological Oncology
https://www.readbyqxmd.com/read/28838937/daratumumab-combinations-what-can-we-learn
#19
Efstathios Kastritis, Meletios A Dimopoulos
No abstract text is available yet for this article.
August 24, 2017: Blood
https://www.readbyqxmd.com/read/28799231/efficacy-of-daratumumab-based-therapies-in-patients-with-relapsed-refractory-multiple-myeloma-treated-outside-of-clinical-trials
#20
Arjun Lakshman, Jithma P Abeykoon, Shaji K Kumar, S Vincent Rajkumar, David Dingli, Francis K Buadi, Wilson I Gonsalves, Nelson Leung, Angela Dispenzieri, Taxiarchis V Kourelis, Ronald S Go, Martha Q Lacy, Miriam A Hobbs, Yi Lin, Rahma Warsame, John Lust, Amie L Fonder, Yi L Hwa, Suzanne R Hayman, Stephen J Russell, Robert A Kyle, Morie A Gertz, Prashant Kapoor
Outside of clinical trials, experience with daratumumab-based combination therapies (DCTs) using bortezomib (V)/lenalidomide (R)/pomalidomide (P), and dexamethasone (d) in relapsed/refractory multiple myeloma (RRMM) is limited. We reviewed the outcomes of 126 patients who received ≥ 1 cycle of any DCT. Median age at DCT initiation was 67 (range, 43-93) years. High-risk cytogenetics was present in 33% patients. Median number of prior therapies was 4 (range, 1-14) and time to first DCT from diagnosis was 4...
November 2017: American Journal of Hematology
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