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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
#1
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
#2
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
#3
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
#4
S Vallet, M Pecherstorfer, K 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)...
August 31, 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
#5
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
#6
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
#7
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...
August 11, 2017: American Journal of Hematology
https://www.readbyqxmd.com/read/28747306/how-i-treat-new-agents-in-myeloma
#8
Philippe Moreau
At present, multiple classes of agents with distinct mechanisms of action are available for the treatment of patients with multiple myeloma (MM), including alkylators, steroids, immunomodulatory agents (IMiDs), proteasome inhibitors (PIs), histone deacetylase inhibitors (DACIs) and monoclonal antibodies (mAbs). Over the last 5 years, several new agents, such as the third-generation IMiD pomalidomide, the second generation PIs carfilzomib and ixazomib, the DACI panobinostat and two monoclonal antibodies, elotuzumab and daratumumab, have been approved, incorporated into clinical guidelines and have transformed our approach to the treatment of patients...
July 26, 2017: Blood
https://www.readbyqxmd.com/read/28734795/monoclonal-antibodies-in-multiple-myeloma-a-new-wave-of-the-future
#9
REVIEW
Daniel W Sherbenou, Tomer M Mark, Peter Forsberg
In 2015, 2 monoclonal antibodies were approved for the treatment of relapsed or refractory multiple myeloma (RRMM), elotuzumab and daratumumab. Elotuzumab is a monoclonal IgG-κ antibody directed against SLAMF7 (signaling lymphocytic activation molecule F7), a cell surface receptor involved in natural killer cell activation. Daratumumab is a monoclonal IgG-κ antibody that binds to CD38, a transmembrane protein found on the surface of myeloma cells and responsible for cellular adhesion and ectoenzymatic activity...
June 27, 2017: Clinical Lymphoma, Myeloma & Leukemia
https://www.readbyqxmd.com/read/28679737/how-i-treat-first-relapse-of-myeloma
#10
Jean Luc Harousseau, Michel Attal
The standard treatment of relapsed multiple myeloma (MM) was either lenalidomide-dexamethasone (RD) or bortezomib-dexamethasone (VD) but it is changing rapidly for two reasons. Firstly lenalidomide and bortezomib are currently used in frontline treatment and many patients become resistant to these agents early in the course of their disease. Secondly six second-line new agents have been recently developed and offer new possibilities (pomalidomide, carfilzomib and ixazomib, panobinostat, elotuzumab and daratumumab)...
July 5, 2017: Blood
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
#11
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/28637662/daratumumab-plus-pomalidomide-and-dexamethasone-in-relapsed-and-or-refractory-multiple-myeloma
#12
Ajai Chari, Attaya Suvannasankha, Joseph W Fay, Bertrand Arnulf, Jonathan L Kaufman, Jainulabdeen J Ifthikharuddin, Brendan M Weiss, Amrita Krishnan, Suzanne Lentzsch, Raymond Comenzo, Jianping Wang, Kerri Nottage, Christopher Chiu, Nushmia Z Khokhar, Tahamtan Ahmadi, Sagar Lonial
Daratumumab plus pomalidomide and dexamethasone (pom-dex) was evaluated in patients with relapsed/refractory multiple myeloma with ≥2 prior lines of therapy who were refractory to their last treatment. Patients received daratumumab 16 mg/kg at the recommended dosing schedule, pomalidomide 4 mg daily for 21 days of each 28-day cycle, and dexamethasone 40 mg weekly. Safety was the primary end point. Overall response rate (ORR) and minimal residual disease (MRD) by next-generation sequencing were secondary end points...
August 24, 2017: Blood
https://www.readbyqxmd.com/read/28615223/daratumumab-yields-rapid-and-deep-hematologic-responses-in-patients-with-heavily-pretreated-al-amyloidosis
#13
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 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...
August 17, 2017: Blood
https://www.readbyqxmd.com/read/28601492/new-agents-in-multiple-myeloma-an%C3%A2-examination-of-safety-profiles
#14
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...
July 2017: Clinical Lymphoma, Myeloma & Leukemia
https://www.readbyqxmd.com/read/28596644/highlights-of-multiple-myeloma-at-the-annual-meeting-of-american-society-of-hematology-2016
#15
REVIEW
Nidhi Tandon, Shaji K Kumar
This review discusses the landmark studies in the field of multiple myeloma (MM) which were presented at American society of hematology annual meeting, 2016. There were contrary results from two large phase III trials (one from US and one from Europe) that evaluated the role of additional interventions like tandem autologous transplant (ASCT) and consolidation after induction therapy followed by ASCT in newly diagnosed MM (NDMM) patients, but there were critical differences between the two studies. Novel agents like carfilzomib and ixazomib proved to be of benefit when used as induction and post ASCT consolidation and maintenance in NDMM...
June 2017: Indian Journal of Hematology & Blood Transfusion
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
#16
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
#17
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)...
July 3, 2017: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/28561703/hematologic-malignancies-plasma-cell-disorders
#18
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
#19
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/28540859/case-report-serological-testing-interference-of-daratumumab-anti-cd38-therapy-in-multiple-myeloma
#20
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
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