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Daratumumab myeloma

Muhammad Husnain, Sandra Kurtin, Nikki Barkett, Irbaz Bin Riaz, Amit Agarwal
Patients with relapsed and refractory multiple myeloma have poor prognosis. A recent analysis of patients with relapsed and refractory multiple myeloma who were refractory to both proteasome inhibitors and immunomodulatory drugs showed the median overall survival of 9 months only. Daratumumab is the first-in-class human monoclonal antibody against CD38 cells which was studied in phase I/II trials for treatment of these patients with relapsed refractory multiple myeloma. It showed an overall response rate of 36% and a median overall survival (OS) of 17 months in these patients...
2016: Case Reports in Oncological Medicine
Holly Baker
No abstract text is available yet for this article.
October 13, 2016: Lancet Oncology
Meletios A Dimopoulos, Albert Oriol, Hareth Nahi, Jesus San-Miguel, Nizar J Bahlis, Saad Z Usmani, Neil Rabin, Robert Z Orlowski, Mieczyslaw Komarnicki, Kenshi Suzuki, Torben Plesner, Sung-Soo Yoon, Dina Ben Yehuda, Paul G Richardson, Hartmut Goldschmidt, Donna Reece, Steen Lisby, Nushmia Z Khokhar, Lisa O'Rourke, Christopher Chiu, Xiang Qin, Mary Guckert, Tahamtan Ahmadi, Philippe Moreau
Background Daratumumab showed promising efficacy alone and with lenalidomide and dexamethasone in a phase 1-2 study involving patients with relapsed or refractory multiple myeloma. Methods In this phase 3 trial, we randomly assigned 569 patients with multiple myeloma who had received one or more previous lines of therapy to receive lenalidomide and dexamethasone either alone (control group) or in combination with daratumumab (daratumumab group). The primary end point was progression-free survival. Results At a median follow-up of 13...
October 6, 2016: New England Journal of Medicine
Michele Moschetta, Yawara Kawano, Klaus Podar
Unprecedented advances in multiple myeloma (MM) therapy during the last 15 years are predominantly based on our increasing understanding of the pathophysiologic role of the bone marrow (BM) microenvironment. Indeed, new treatment paradigms, which incorporate thalidomide, immunomodulatory drugs (IMiDs), and proteasome inhibitors, target the tumor cell as well as its BM microenvironment. Ongoing translational research aims to understand in more detail how disordered BM-niche functions contribute to MM pathogenesis and to identify additional derived targeting agents...
2016: Cancer Treatment and Research
Peter M Voorhees, Saad Z Usmani
The advent of the immunomodulatory drugs thalido-mide, lenalidomide, and pomalidomide; the proteasome inhib-itors bortezomib, carfilzomib, and ixazomib; the histone deacet-ylase inhibitor panobinostat; and the monoclonal antibodies elotuzumab and daratumumab has led to dramatic improvements in outcomes for patients with multiple myeloma. Along with progress in nontransplant therapy have come questions regarding the continued role of high-dose melphalan (HDM) supported by autologous stem cell transplant (ASCT) in the treatment of multiple myeloma...
September 2016: Clinical Advances in Hematology & Oncology: H&O
Lisa A Raedler
No abstract text is available yet for this article.
March 2016: American Health & Drug Benefits
Kazunori Murata, Samuel I McCash, Brittany Carroll, Alexander M Lesokhin, Hani Hassoun, Nikoletta Lendvai, Neha S Korde, Sham Mailankody, Heather J Landau, Guenther Koehne, David J Chung, Sergio A Giralt, Lakshmi V Ramanathan, Ola Landgren
OBJECTIVES: To characterize the effect of three humanized IgG κ monoclonal antibodies (daratumumab, isatuximab, and elotuzumab) on the interpretation of results generated by protein electrophoresis, immunofixation, free light chain, and heavy/light chain assays performed on human serum. METHODS: Healthy volunteer serum and serum from multiple myeloma patients were supplemented with clinically relevant concentrations of each of the three monoclonal antibodies. These specimens then underwent analysis via serum protein electrophoresis, immunofixation, serum free light chain quantification, heavy/light chain quantification, total IgG, and total protein...
September 21, 2016: Clinical Biochemistry
Laurent Garderet, Gordon Cook, Holger W Auner, Benedetto Bruno, Henk Lokhorst, Jose Antonio Perez-Simon, Firoozeh Sahebi, Christof Scheid, Curly Morris, Anja van Biezen, Mohamad Sobh, Mauricette Michallet, Gösta Gahrton, Stefan Schönland, Nicolaus Kröger
Major improvements have been made in the treatment of myeloma. However, all patients, perhaps with some exceptions, eventually relapse, even after autologous stem cell transplantation (ASCT). In that setting, the combinations of new drugs, namely the IMiDs and the proteasome inhibitors along with steroids, give encouraging results in relapsed patients. The median progression-free survival (PFS) is 20 months with lenalidomide plus dexamethasone plus ixazomib and 26 months with lenalidomide plus dexamethasone plus carfilzomib...
September 21, 2016: Leukemia & Lymphoma
(no author information available yet)
A phase III trial suggests that the combination of daratumumab, bortezomib, and dexamethasone is more powerful in patients with relapsed or relapsed and refractory melanoma than bortezomib plus dexamethasone. Patients who received all three drugs had a higher overall response rate and improved 12-month progression-free survival.
September 14, 2016: Cancer Discovery
Junshik Hong, Jae Hoon Lee
Epidemiologically, multiple myeloma (MM) is a malignant disorder of plasma cells with a higher incidence among Western populations than among Asians. However, there is growing evidence of a recent increase in the age-standardized incidence rate (ASR) of MM in Asian countries, particularly Korea. Application of novel agents has resulted in significant improvement of treatment outcomes, and the advances are ongoing with the recent introduction and U.S. Food and Drug Administration's approval of newer agents, including carfilzomib, ixazomib, elotuzumab, and daratumumab...
September 2016: Korean Journal of Internal Medicine
Manjulika Das
No abstract text is available yet for this article.
October 2016: Lancet Oncology
James W Larrick, Mark R Alfenito, Jamie K Scott, Paul W H I Parren, Dennis R Burton, Andrew R M Bradbury, Cynthia A Lemere, Anne Messer, James S Huston, Paul J Carter, Trudi Veldman, Kerry A Chester, Janine Schuurman, Gregory P Adams, Janice M Reichert
Antibody Engineering & Therapeutics, the largest meeting devoted to antibody science and technology and the annual meeting of The Antibody Society, will be held in San Diego, CA on December 11-15, 2016. Each of 14 sessions will include six presentations by leading industry and academic experts. In this meeting preview, the session chairs discuss the relevance of their topics to current and future antibody therapeutics development. Session topics include bispecifics and designer polyclonal antibodies; antibodies for neurodegenerative diseases; the interface between passive and active immunotherapy; antibodies for non-cancer indications; novel antibody display, selection and screening technologies; novel checkpoint modulators / immuno-oncology; engineering antibodies for T-cell therapy; novel engineering strategies to enhance antibody functions; and the biological Impact of Fc receptor engagement...
August 24, 2016: MAbs
Antonio Palumbo, Asher Chanan-Khan, Katja Weisel, Ajay K Nooka, Tamas Masszi, Meral Beksac, Ivan Spicka, Vania Hungria, Markus Munder, Maria V Mateos, Tomer M Mark, Ming Qi, Jordan Schecter, Himal Amin, Xiang Qin, William Deraedt, Tahamtan Ahmadi, Andrew Spencer, Pieter Sonneveld
BACKGROUND: Daratumumab, a human IgGκ monoclonal antibody that targets CD38, induces direct and indirect antimyeloma activity and has shown substantial efficacy as monotherapy in heavily pretreated patients with multiple myeloma, as well as in combination with bortezomib in patients with newly diagnosed multiple myeloma. METHODS: In this phase 3 trial, we randomly assigned 498 patients with relapsed or relapsed and refractory multiple myeloma to receive bortezomib (1...
August 25, 2016: New England Journal of Medicine
Torben Plesner, Hendrik-Tobias Arkenau, Peter Gimsing, Jakub Krejcik, Charlotte Lemech, Monique C Minnema, Ulrik Lassen, Jacob P Laubach, Antonio Palumbo, Steen Lisby, Linda Basse, Jianping Wang, A Kate Sasser, Mary E Guckert, Carla de Boer, Nushmia Z Khokhar, Howard Yeh, Pamela L Clemens, Tahamtan Ahmadi, Henk M Lokhorst, Paul G Richardson
Daratumumab, a human CD38 IgG1κ monoclonal antibody, has activity as monotherapy in multiple myeloma (MM). This phase 1/2 study investigated daratumumab plus lenalidomide/dexamethasone in refractory and relapsed/refractory MM. Part 1 (dose-escalation) evaluated 4 daratumumab doses plus lenalidomide (25 mg/day p.o. on Days 1 21 of each cycle) and dexamethasone (40 mg/week). Part 2 (dose-expansion) evaluated daratumumab at the recommended phase 2 dose (RP2D) plus lenalidomide/dexamethasone. Safety, efficacy, pharmacokinetics, immunogenicity and accelerated daratumumab infusions were studied...
August 16, 2016: Blood
Aaron Seth Rosenberg, Scott Bainbridge, Roma Pahwa, Ishwarlal Jialal
OBJECTIVES: Recently monoclonal antibody therapy has been introduced in the treatment of multiple Myeloma (MM). One such efficacious therapy is the anti-CD38 monoclonal antibody, daratumumab (Dara). Since it is an Ig-G-kappa it can interfere with both the serum protein electrophoresis and immunofixation electrophoresis (IFE). The free light chain (FLC) assay is also useful in the diagnosis and therapeutic monitoring of MM. Hence we tested the effect of Dara on the FLC assay. METHODS: 30 serum samples from patients with known IgG-kappa (n=20) and non-IgG-kappa M -proteins (n=10) were spiked with Dara at a final concentration of 1...
October 2016: Clinical Biochemistry
A M Rajan, S Kumar
The treatment of multiple myeloma (MM) is rapidly evolving. In the United States, four drugs (panobinostat, ixazomib, daratumumab and elotuzumab) were approved for the treatment of MM in 2015. As a result of improved diagnosis and therapy, there has been a dramatic improvement in the outcome of MM in the last decade, probably more than any other malignancy. Numerous agents continue to be studied in preclinical models and in clinical trials, with many demonstrating clinical efficacy that appears promising enough to have a trajectory for regulatory approval...
2016: Blood Cancer Journal
Karen M K De Vooght, Marlies Oostendorp, Wouter W van Solinge
PURPOSE OF REVIEW: Immunotherapeutic strategies are emerging as novel therapeutic approaches in multiple myeloma, with several mAbs being in advanced stages of clinical development. Of these, CD38 targeting antibodies appear very promising. In trials with anti-CD38 mAb daratumumab, all patients demonstrated panreactivity in red blood cell (RBC) panel testing, complicating the selection of compatible RBCs for transfusion. This review provides an overview of the interferences and solutions to safely transfuse these patients...
November 2016: Current Opinion in Hematology
Larysa Sanchez, Yucai Wang, David S Siegel, Michael L Wang
Daratumumab is a human monoclonal antibody that targets CD38, a cell surface protein that is overexpressed on multiple myeloma (MM) cells. Preclinical studies have shown that daratumumab induces MM cell death through several mechanisms, including complement-dependent cytotoxicity (CDC), antibody-dependent cell-mediated cytotoxicity (ADCC), antibody-dependent cellular phagocytosis (ADCP), and apoptosis. Given the encouraging efficacy and acceptable safety profile of daratumumab demonstrated in clinical trials, daratumumab has emerged as a novel treatment option for myeloma and became the first monoclonal antibody approved by the FDA for the treatment of MM...
2016: Journal of Hematology & Oncology
Leonard Naymagon, Maher Abdul-Hay
Multiple myeloma (MM) is a disease that affects plasma cells and can lead to devastating clinical features such as anemia, lytic bone lesions, hypercalcemia, and renal disease. An enhanced understanding of MM disease mechanisms has led to new more targeted treatments. There is now a plethora of treatments available for MM. In this review article, our aim is to discuss many of the novel agents that are being studied or have recently been approved for the treatment of MM. These agents include the following: immunomodulators (pomalidomide), proteasome inhibitors (carfilzomib, marizomib, ixazomib, oprozomib), alkylating agents (bendamustine), AKT inhibitors (afuresertib), BTK inhibitors (ibrutinib), CDK inhibitors (dinaciclib), histone deacetylase inhibitors (panobinostat, rocilinostat, vorinostat), IL-6 inhibitors (siltuximab), kinesin spindle protein inhibitors (filanesib), monoclonal antibodies (daratumumab, elotuzumab, indatuximab, SAR650984), and phosphoinositide 3-kinase (PI3K) inhibitors...
2016: Journal of Hematology & Oncology
Marije B Overdijk, J H Marco Jansen, Maaike Nederend, Jeroen J Lammerts van Bueren, Richard W J Groen, Paul W H I Parren, Jeanette H W Leusen, Peter Boross
Emerging evidence suggests that FcγR-mediated cross-linking of tumor-bound mAbs may induce signaling in tumor cells that contributes to their therapeutic activity. In this study, we show that daratumumab (DARA), a therapeutic human CD38 mAb with a broad-spectrum killing activity, is able to induce programmed cell death (PCD) of CD38(+) multiple myeloma tumor cell lines when cross-linked in vitro by secondary Abs or via an FcγR. By comparing DARA efficacy in a syngeneic in vivo tumor model using FcRγ-chain knockout or NOTAM mice carrying a signaling-inactive FcRγ-chain, we found that the inhibitory FcγRIIb as well as activating FcγRs induce DARA cross-linking-mediated PCD...
August 1, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
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