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Daratumumab myeloma

Jane Cho, Nicole Siegel, Manju L Subramanian, Howard Ying, Steven Ness
PURPOSE: To describe a case of neovascular glaucoma from cytomegalovirus (CMV) retinitis in a human immunodeficiency virus-negative patient with immunosuppression after stem-cell transplant for multiple myeloma. METHODS: Retrospective case report. RESULTS: A 71-year-old man on monthly infusion of daratumumab for multiple myeloma after stem-cell transplant presenting with a 2-week history of floaters, photophobia, and blurry vision was found to have polymerase chain reaction-confirmed CMV retinitis associated with diffuse occlusive vasculitis...
March 12, 2018: Retinal Cases & Brief Reports
Carolina Bonet Bub, Isabel Nagle Dos Reis, Maria Giselda Aravechia, Leandro Dinalli Santos, Eduardo Peres Bastos, José Mauro Kutner, Lilian Castilho
INTRODUCTION: Pre-transfusion tests, essential for the release of blood components, may be affected by drugs. Monoclonal antibodies represent a class of medications increasingly used in the clinical practice, with anti-CD38 monoclonal antibodies (daratumumab) being a promising resource in the treatment of refractory myeloma. This monoclonal antibody recognizes CD38 in myeloma cells and interferes with pre-transfusion tests by causing panreactivity in indirect antiglobulin tests thereby clinically masking alloantibodies...
January 2018: Revista Brasileira de Hematologia e Hemoterapia
Niken M Mahaweni, Gerard M J Bos, Constantine S Mitsiades, Marcel G J Tilanus, Lotte Wieten
Natural killer (NK) cell-based immunotherapy is a promising novel approach to treat cancer. However, NK cell function has been shown to be potentially diminished by factors common in the tumor microenvironment (TME). In this study, we assessed the synergistic potential of antibody-dependent cell-mediated cytotoxicity (ADCC) and killer immunoglobin-like receptor (KIR)-ligand mismatched NK cells to potentiate NK cell antitumor reactivity in multiple myeloma (MM). Hypoxia, lactate, prostaglandin E2 (PGE2) or combinations were selected to mimic the TME...
March 2, 2018: Cancer Immunology, Immunotherapy: CII
Eric M Maiese, Claire Ainsworth, Jean-Gabriel Le Moine, Outi Ahdesmäki, Judith Bell, Emma Hawe
PURPOSE: New therapies, including daratumumab plus lenalidomide plus dexamethasone (DRd) and daratumumab plus bortezomib plus dexamethasone (DVd), have recently been approved in the United States for patients with multiple myeloma (MM) who have received at least 1 prior line of therapy. However, few treatments have been compared in head-to-head clinical trials to determine the most efficacious therapy. In an update of the POLLUX (Phase 3 Study Comparing DRd Versus Rd in Subjects with Relapsed or Refractory Multiple Myeloma [RRMM]) trial, median progression-free survival (PFS) for DRd was not reached; the hazard ratio compared with Rd was 0...
February 27, 2018: Clinical Therapeutics
Marina Bolzoni, Denise Toscani, Paola Storti, Valentina Marchica, Federica Costa, Nicola Giuliani
Bone destruction is the hallmark of multiple myeloma (MM). About 80% of MM patients at diagnosis presents myeloma bone disease (MBD) leading to bone pain and pathological fractures, significantly affecting patients' quality of life. Bisphosphonates are the treatment of choice for MBD, but osteolytic lesions remain a critical issue in the current management of MM patients. Several studies clarified the mechanisms involved in MM-induced osteoclast formation and activation, leading to the identification of new possible targets and the development of better bone-directed therapies, that are discussed in this review...
March 2, 2018: Expert Review of Hematology
Francisca Guijarro, María Rozman, Estella Matutes
No abstract text is available yet for this article.
February 22, 2018: British Journal of Haematology
Kristine A Frerichs, Noemi Anna Nagy, Pieter L Lindenbergh, Patty Bosman, Jhon Marin Soto, Marloes Broekmans, Richard W J Groen, Maria Themeli, Louise Nieuwenhuis, Claudia Stege, Inger S Nijhof, Tuna Mutis, Sonja Zweegman, Henk M Lokhorst, Niels W C J van de Donk
Multiple myeloma (MM) is generally an incurable hematological malignancy with heterogeneous overall survival rates ranging from a few months to more than 10 years. Survival is especially poor for patients who developed disease that is refractory to immunomodulatory drugs and proteasome inhibitors. Areas covered: This review will discuss the importance of CD38-targeting antibodies for the treatment of MM patients to improve their outcome. Expert commentary: Intense immuno-oncological laboratory research has resulted in the development of functionally active monoclonal antibodies against cell surface markers present on MM cells...
March 2018: Expert Review of Clinical Immunology
Meletios Athanasios Dimopoulos, Jonathan L Kaufman, Darrell White, Gordon Cook, Maria Rizzo, Yingxin Xu, Kyle Fahrbach, Maren Gaudig, Mary Slavcev, Lindsay Dearden, Annette Lam
BACKGROUND: Previous network meta-analyses combined studies of immunomodulatory drug (IMiD)-containing and IMiD-free regimens, despite a lack of head-to-head randomized controlled trials to robustly link them. However, patients with relapsed or refractory multiple myeloma (RRMM) treated with IMiD-containing regimens differ from those treated with IMiD-free regimens, especially relating to treatment history, which is an important treatment-effect modifier requiring clinical consideration when evaluating the most appropriate subsequent treatment options...
January 5, 2018: Clinical Lymphoma, Myeloma & Leukemia
M Pick, V Vainstein, N Goldschmidt, D Lavie, D Libster, A Gural, S Grisariu, B Avni, D Ben Yehuda, M E Gatt
OBJECTIVE: Daratumumab is a promising new anti-myeloma agent. We report a single center "real world" series of multiple myeloma (MM) and amyloidosis (AL) patients treated with daratumumab. METHODS: Forty-one patients were included: 7 second line MM, 30 heavily pretreated (median number of therapies of 5) advanced MM, and 4 with AL. RESULTS: Second line patients and advanced AL showed high rate of durable overall responses. However, advanced MM patients had a dismal prognosis with an ORR of 36%, and a short median progression free and overall survival of 2...
February 17, 2018: European Journal of Haematology
Lei Kang, Dawei Jiang, Christopher G England, Todd E Barnhart, Bo Yu, Zachary T Rosenkrans, Rongfu Wang, Jonathan W Engle, Xiaojie Xu, Peng Huang, Weibo Cai
PURPOSE: CD38 is considered a potential biomarker for multiple myeloma (MM) and has shown a strong link with chronic lymphocytic leukemia due to high and uniform expression on plasma cells. In vivo evaluation of CD38 expression may provide useful information about lesion detection and prognosis of treatment in MM. In this study, immunoPET imaging with89 Zr-labeled daratumumab was used for differentiation of CD38 expression in murine lymphoma models to provide a potential non-invasive method for monitoring CD38 in the clinic...
February 15, 2018: European Journal of Nuclear Medicine and Molecular Imaging
Saad Z Usmani, Imran Khan, Christopher Chiu, David Foureau, Lawrence J Druhan, Katherine Rigby, Tineke Casneuf, A Kate Sasser
Background: Daratumumab, a human CD38 monoclonal antibody that has direct on-tumor and immunomodulatory mechanisms of action, demonstrated clinical benefit as monotherapy or in combination with established regimens in patients with multiple myeloma with one or more prior lines of therapy. Case presentation: A male patient, who was 70 years of age at the time of diagnosis of multiple myeloma in 2011, relapsed after five lines of therapy, including autologous stem cell transplantation...
2018: Experimental Hematology & Oncology
Marina Zajec, Joannes F M Jacobs, Patricia J T A Groenen, Corrie M de Kat Angelino, Christoph Stingl, Theo M Luider, Yolanda B De Rijke, Martijn M VanDuijn
M-protein diagnostics can be compromised for patients receiving therapeutic monoclonal antibodies as treatment in multiple myeloma. Conventional techniques are often not able to distinguish between M-proteins and therapeutic monoclonal antibodies administered to the patient. This may prevent correct response assessment and can lead to overtreatment. We have developed a serum-based targeted mass spectrometry assay to detect M-proteins, even in the presence of three therapeutic monoclonal antibodies (daratumumab, ipilimumab and nivolumab)...
February 9, 2018: Journal of Proteome Research
Hang Quach, Simon Benson, Helen Haysom, Anne-Marie Wilkes, Nicole Zacher, Merrole Cole-Sinclair, Henry Miles Prince, Peter Mollee, Andrew Spencer, Phoebe Joy Ho, Simon J Harrison, Cindy Lee, Bradley Augustson, James Daly
In recent years, the anti-CD38 monoclonal antibody daratumumab (Darzalex; Janssen-Cilag Pty Ltd) has been shown to be highly efficacious in relapsed and refractory multiple myeloma, with the final results of treatment in newly diagnosed patients awaited. Despite awareness of the potential interference of daratumumab in pre-transfusion immunohaematology testing during phase I and II clinical studies, there was a degree of unpreparedness in the community upon the introduction of this drug into the clinics, particularly the impact that it has on the operational processes in hospital transfusion laboratories and timely issue of red blood cells (RBCs)...
February 2018: Internal Medicine Journal
Kyriaki Tzogani, Elisabeth Penninga, Marie Louise Schougaard Christiansen, Doris Hovgaard, Sinan B Sarac, Jorge Camarero Jimenez, Isabel Garcia, Marta Lafuente, Arantxa Sancho-López, Tomas Salmonson, Christian Gisselbrecht, Francesco Pignatti
On May 20, 2016, a conditional marketing authorization valid through the European Union (EU) was issued for daratumumab as monotherapy for the treatment of adult patients with relapsed and refractory multiple myeloma, whose prior therapy included a proteasome inhibitor (PI) and an immunomodulatory drug (IMiD) and who had demonstrated disease progression on the last therapy. The review of daratumumab was conducted under the EMA's accelerated assessment program for drugs that are of major interest for public health, especially from the point of view of therapeutic innovation...
January 25, 2018: Oncologist
G Carreño-Tarragona, T Cedena, L Montejano, R Alonso, F Miras, A Valeri, A Rivero, J J Lahuerta, J Martinez-Lopez
OBJECTIVES: To report our 2 years of experience navigating the interference of anti-CD38 monoclonal antibodies (MAs) in 33 patients and describe papain-treated panels as a complementary method to dithiothreitol (DTT). BACKGROUND: Novel anti-CD38 MAs are now approved or undergoing clinical trials to evaluate their activity in patients with multiple myeloma. A concern with the use of these drugs is that they interfere with blood bank tests in a group of patients who often require blood transfusions...
January 25, 2018: Transfusion Medicine
Hannah A Blair
The author has alerted us to the following error in Sect., and the following correction should be noted.
January 24, 2018: Drugs
V Deneys, C Thiry, A Frelik, C Debry, B Martin, C Doyen
OBJECTIVES: Recently, daratumumab has been included in the therapeutic strategies for myeloma patients. This molecule is an antibody directed against CD38, strongly expressed on plasma cells. Nevertheless, as CD38 is also present on erythrocyte membrane, daratumumab interferes with immunohaematological tests, complicating the selection of compatible blood. METHODS: A total of 14 patients treated by daratumumab have been followed in our transfusion laboratory. Among them, 11 have been transfused...
January 11, 2018: Transfusion Clinique et Biologique: Journal de la Société Française de Transfusion Sanguine
Peter Sidaway
No abstract text is available yet for this article.
March 2018: Nature Reviews. Clinical Oncology
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
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
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