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https://www.readbyqxmd.com/read/29768064/a-look-at-treatment-strategies-for-relapsed-multiple-myeloma
#1
Giusy Cetani, Mario Boccadoro, Stefania Oliva
Multiple myeloma treatment considerably improved during the past decade, thanks to novel effective drugs, a better understanding of myeloma biology and clonal heterogeneity, and an improved management of toxicities. The choice of regimen at relapse is usually based on prior response, toxicities, age and comorbidities of relapsed patients. Areas covered: A review was performed of the most recent and effective therapeutic strategies for the relapsed myeloma setting, by documenting the latest clinical evidence from phase II and III clinical trials...
May 16, 2018: Expert Review of Anticancer Therapy
https://www.readbyqxmd.com/read/29761078/novel-immunotherapy-options-for-extranodal-nk-t-cell-lymphoma
#2
REVIEW
Boyu Hu, Yasuhiro Oki
Extranodal NK/T-cell lymphoma (ENKTCL) is a highly aggressive mature NK/T-cell neoplasm marked by NK-cell phenotypic expression of CD3ε and CD56. While the disease is reported worldwide, there is a significant geographic variation with its highest incidence in East Asian countries possibly related to the frequent early childhood exposure of Epstein-Barr virus (EBV) and specific ethnic-genetical background, which contributes to the tumorigenesis. Historically, anthracycline-based chemotherapy such as CHOP (cyclophosphamide, adriamycin, vincristine, and prednisone) was used, but resulted in poor outcomes...
2018: Frontiers in Oncology
https://www.readbyqxmd.com/read/29756564/clinical-and-pharmacologic-features-of-monoclonal-antibodies-and-checkpoint-blockade-therapy-in-multiple-myeloma
#3
Mattia D'Agostino, Giulia Gazzera, Giusy Cetani, Sara Bringhen, Mario Boccadoro, Francesca Gay
BACKGROUND: Survival of multiple myeloma patients has considerably improved in the last decades thanks to the introduction of many new drugs, including immunomodulatory agents, proteasome inhibitors and, more recently, monoclonal antibodies. METHODS: We analyzed the most recent literature focusing on the clinical and pharmacologic aspects of monoclonal antibody-based therapies in multiple myeloma, including monoclonal antibodies directed against plasma cell antigens, as well as checkpoint blockade therapy directed against immune inhibitory molecules, used as single agents or in combination therapy...
May 13, 2018: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/29748955/investigational-agents-in-immunotherapy-a-new-horizon-for-the-treatment-of-multiple-myeloma
#4
REVIEW
Cindy Varga, Jacob P Laubach, Kenneth C Anderson, Paul G Richardson
The treatment of multiple myeloma (MM) has gone through several major advances over the last 5 years with the introduction of next generation proteasome inhibitors (PI; carfilzomib, ixazomib) and immunomodulatory derivatives (IMiD; pomalidomide), with these new agents having a substantial impact on patient outcome. However, despite these advances, MM remains a highly resistant disease given its propensity for clonal heterogeneity and its complex interaction with the surrounding bone marrow microenvironment...
May 10, 2018: British Journal of Haematology
https://www.readbyqxmd.com/read/29742565/current-challenges-and-opportunities-in-the-management-of-antibody-mediated-rejection-in-lung-transplantation
#5
Amanda L Hulbert, Elizabeth N Pavlisko, Scott M Palmer
PURPOSE OF REVIEW: There is increasing recognition of the importance of antibody-mediated rejection (AMR) after lung transplantation. The development of donor-specific antibodies, a key feature of AMR, occurs in approximately 30% of lung transplant recipients and is associated with poor posttransplant outcomes. This review highlights recently developed AMR diagnostic criteria in lung transplantation, potential mechanisms that mediate the development of AMR, and discusses current and emerging treatment strategies for this significant, graft-limiting complication...
June 2018: Current Opinion in Organ Transplantation
https://www.readbyqxmd.com/read/29741423/propensity-score-matching-analysis-to-evaluate-the-comparative-effectiveness-of-daratumumab-versus-real-world-standard-of-care-therapies-for-patients-with-heavily-pretreated-and-refractory-multiple-myeloma
#6
Shaji Kumar, Brian Durie, Hareth Nahi, Ravi Vij, Meletios A Dimopoulos, Efstathios Kastritis, Evangelos Terpos, Xavier Leleu, Meral Beksac, Hartmut Goldschmidt, Jens Hillengass, Zhuo Su, Brian Hutton, Chris Cameron, Imran Khan, Annette Lam
Daratumumab is a CD38-directed monoclonal antibody approved for treating multiple myeloma (MM). Propensity score matching (PSM) based on individual patient data (IPD) was conducted to compare overall survival (OS) and progression-free survival (PFS) for daratumumab versus real-world standard of care (SOC). IPD for patients with relapsed and refractory (RR) MM treated with daratumumab monotherapy were from the GEN501 and SIRIUS studies; IPD for patients treated with SOC were from an International Myeloma Working Group (IMWG) chart review of patients with RRMM...
May 9, 2018: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/29720240/integrative-analysis-reveals-cd38-as-a-therapeutic-target-for-plasma-cell-rich-pre-disease-and-established-rheumatoid-arthritis-and-systemic-lupus-erythematosus
#7
Suzanne Cole, Alice Walsh, Xuefeng Yin, Mihir D Wechalekar, Malcolm D Smith, Susanna M Proudman, Douglas J Veale, Ursula Fearon, Costantino Pitzalis, Frances Humby, Michele Bombardieri, Amy Axel, Homer Adams, Christopher Chiu, Michael Sharp, John Alvarez, Ian Anderson, Loui Madakamutil, Sunil Nagpal, Yanxia Guo
BACKGROUND: Plasmablasts and plasma cells play a key role in many autoimmune diseases, such as rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). This study was undertaken to evaluate the potential of targeting CD38 as a plasma cell/plasmablast depletion mechanism by daratumumab in the treatment of patients with RA and SLE. METHODS: RNA-sequencing analysis of synovial biopsies from various stages of RA disease progression, flow cytometry analysis of peripheral blood mononuclear cells (PBMC) from patients with RA or SLE and healthy donors, immunohistochemistry assessment (IHC) of synovial biopsies from patients with early RA, and ex vivo immune cell depletion assays using daratumumab (an anti-CD38 monoclonal antibody) were used to assess CD38 as a therapeutic target...
May 2, 2018: Arthritis Research & Therapy
https://www.readbyqxmd.com/read/29714573/a-pilot-experiment-in-responding-to-individual-patient-requests-for-compassionate-use-of-an-unapproved-drug-the-compassionate-use-advisory-committee-compac
#8
Arthur Caplan, Alison Bateman-House, Joanne Waldstreicher, Lisa Fedor, Ramana Sonty, Tito Roccia, Jon Ukropec, Rick Jansson
BACKGROUND: Janssen Research & Development, LLC, part of the Janssen pharmaceutical companies of Johnson & Johnson, and NYU School of Medicine partnered to establish the Compassionate Use Advisory Committee (CompAC) to evaluate the use of an independent, external, expert committee in ensuring transparent, fair, beneficent, evidence-based, and patient-focused compassionate access to investigational medicines, a public health challenge that has been an ongoing issue for over 3 decades...
January 1, 2018: Therapeutic Innovation & Regulatory Science
https://www.readbyqxmd.com/read/29712896/daratumumab-lenalidomide-and-dexamethasone-in-east-asian-patients-with-relapsed-or-refractory-multiple-myeloma-subgroup-analyses-of-the-phase-3-pollux-study
#9
Kenshi Suzuki, Meletios A Dimopoulos, Naoki Takezako, Shinichiro Okamoto, Atsushi Shinagawa, Morio Matsumoto, Hiroshi Kosugi, Sung-Soo Yoon, Shang-Yi Huang, Xiang Qin, Ming Qi, Shinsuke Iida
In the phase 3 POLLUX study, daratumumab plus lenalidomide and dexamethasone (DRd) significantly reduced the risk of progression/death and induced deeper responses vs. lenalidomide and dexamethasone alone (Rd) in patients with relapsed/refractory multiple myeloma (RRMM). We report a subgroup analysis of East Asian (Japanese, Korean, and Taiwanese) patients from POLLUX based on a longer follow-up of 24.7 months. Median progression-free survival was not reached (NR) for DRd vs. 13.8 months for Rd (hazard ratio [HR], 0...
May 1, 2018: Blood Cancer Journal
https://www.readbyqxmd.com/read/29702148/immunomodulatory-effects-of-cd38-targeting-antibodies
#10
REVIEW
Niels W C J van de Donk
The fist in class CD38-targeting antibody, daratumumab, is currently approved as single agent and in combination with standards of care for the treatment of relapsed and refractory multiple myeloma. Based on the high activity and favorable toxicity profile of daratumumab, other CD38 antibodies, such as isatuximab, MOR202, and TAK-079, are being evaluated in MM and other malignancies. The CD38-targeting antibodies have classic Fc-dependent immune effector mechanisms, including antibody-dependent cellular cytotoxicity (ADCC), antibody-dependent cellular phagocytosis (ADCP), and complement-dependent cytotoxicity (CDC)...
April 24, 2018: Immunology Letters
https://www.readbyqxmd.com/read/29696629/current-use-of-monoclonal-antibodies-in-the-treatment-of-multiple-myeloma
#11
REVIEW
Cindy Varga, Michelle Maglio, Irene M Ghobrial, Paul G Richardson
Multiple myeloma (MM) is the second most common haematological malignancy after non-Hodgkin lymphoma. Despite the improvement in outcomes over the last decade with the introduction of novel therapies, such as immunomodulatory agents (IMiDs) and proteasome inhibitors (PIs), MM remains an incurable disease. Patients who are both refractory to IMiDs and PIs carry a particularly dismal prognosis. The development of targeted therapy in the form of monoclonal antibodies has shifted the treatment paradigm of this disease, resulting in unprecedented response rates, even among the highest-risk patients...
April 25, 2018: British Journal of Haematology
https://www.readbyqxmd.com/read/29679038/ninety-minute-daratumumab-infusion-is-safe-in-multiple-myeloma
#12
Hallie Barr, Jessica Dempsey, Allyson Waller, Ying Huang, Nita Williams, Nidhi Sharma, Don M Benson, Ashley E Rosko, Yvonne A Efebera, Craig C Hofmeister
No abstract text is available yet for this article.
March 31, 2018: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/29666301/fratricide-of-nk-cells-in-daratumumab-therapy-for-multiple-myeloma-overcome-by-ex-vivo-expanded-autologous-nk-cells
#13
Yufeng Wang, Yibo Zhang, Tiffany Hughes, Jianying Zhang, Michael A Caligiuri, Don M Benson, Jianhua Yu
PURPOSE: Daratumumab and its use in combination with other agents is becoming a new standard of care for treatment of multiple myeloma (MM). We mechanistically studied how daratumumab acts on NK cells. EXPERIMENTAL DESIGN: Quantities of NK cells in peripheral blood (PB) and/or bone marrow (BM) of MM patients or healthy donors were examined by flow cytometry. NK cell apoptosis and the associated mechanism were assessed by flow cytometry and immunoblotting. Patients' NK cells were expanded in vitro using feeder cells...
April 17, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29622654/safety-and-efficacy-of-daratumumab-in-dialysis-dependent-renal-failure-secondary-to-multiple-myeloma
#14
Serena Rocchi, Paola Tacchetti, Lucia Pantani, Katia Mancuso, Beatrice Zannetti, Michele Cavo, Elena Zamagni
No abstract text is available yet for this article.
April 5, 2018: Haematologica
https://www.readbyqxmd.com/read/29582696/anti-cd38-and-anti-slamf7-the-future-of-myeloma-immunotherapy
#15
Elena Zamagni, Paola Tacchetti, Lucia Pantani, Michele Cavo
the high expression of a number of surface antigens on malignant plasma cells, the bone marrow micro-environment and immune effector T cells, makes these appealing targets for immune therapy with monoclonal antibodies (mAbs). Areas covered: Two mAbs, anti-CD38 daratumumab (Dara) and anti-SLAMF7 elotuzumab (Elo), have achieved recent regulatory approval for relapsed or refractory MM (RRMM) and are currently being explored as possible treatment options in novel combinations and different settings. This review discusses the current landscape and possible development of anti-CD38 and anti-SLAMF7 mAbs...
May 2018: Expert Review of Hematology
https://www.readbyqxmd.com/read/29572070/escmid-study-group-for-infections-in-compromised-hosts-esgich-consensus-document-on-the-safety-of-targeted-and-biological-therapies-an-infectious-diseases-perspective-agents-targeting-lymphoid-or-myeloid-cells-surface-antigens-ii-cd22-cd30-cd33-cd38-cd40-slamf
#16
REVIEW
Lubos Drgona, Carlota Gudiol, Simone Lanini, Bernd Salzberger, Giuseppe Ippolito, Małgorzata Mikulska
BACKGROUND: The present review is part of the ESCMID Study Group for Infections in Compromised Hosts (ESGICH) Consensus Document on the safety of targeted and biological therapies. AIMS: To review, from an Infectious Diseases perspective, the safety profile of agents targeting CD22, CD30, CD33, CD38, CD40, SLAMF-7 and CCR4 and to suggest preventive recommendations. SOURCES: Computer-based MEDLINE searches with MeSH terms pertaining to each agent or therapeutic family...
March 20, 2018: Clinical Microbiology and Infection
https://www.readbyqxmd.com/read/29533389/rapidly-progressive-neovascular-glaucoma-from-cytomegalovirus-retinitis-in-a-non-human-immunodeficiency-virus-patient
#17
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
https://www.readbyqxmd.com/read/29519368/transfusion-management-for-patients-taking-an-anti-cd38-monoclonal-antibody
#18
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
https://www.readbyqxmd.com/read/29512161/extending-shelf-life-of-dithiothreitol-treated-panel-rbcs-to-28-days
#19
J-P Sigle, B Mihm, R Suna, M Bargetzi
BACKGROUND: Daratumumab (DARA) causes non-specific results in indirect agglutination testing (IAT). Dithiothreitol (DTT) treatment of panel red blood cells (RBCs) abolishes DARA interference. The objective of our study was to extend stability of DTT-treated panel RBCs to 28 days through application of a commercially available panel RBC stabilizer. MATERIALS AND METHODS: Serological antigen typing and IAT using DARA sera and DARA plasma spiked with weakly reacting alloantibodies was performed up to 28 days after DTT treatment and stabilization...
March 7, 2018: Vox Sanguinis
https://www.readbyqxmd.com/read/29508033/development-of-an-analytical-method-to-assess-the-occupational-health-risk-of-therapeutic-monoclonal-antibodies-using-lc-hrms
#20
Lars M H Reinders, Martin D Klassen, Martin Jaeger, Thorsten Teutenberg, Jochen Tuerk
Monoclonal antibodies are a group of commonly used therapeutics, whose occupational health risk is still discussed controversially. The long-term low-dose exposure side effects are insufficiently evaluated; hence, discussions are often based on a theoretical level or extrapolating side effects from therapeutic dosages. While some research groups recommend applying the precautionary principle for monoclonal antibodies, others consider the exposure risk too low for measures taken towards occupational health and safety...
April 2018: Analytical and Bioanalytical Chemistry
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