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brentuximab vedotin

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https://www.readbyqxmd.com/read/28441111/phase-ii-study-of-the-efficacy-and-safety-of-pembrolizumab-for-relapsed-refractory-classic-hodgkin-lymphoma
#1
Robert Chen, Pier Luigi Zinzani, Michelle A Fanale, Philippe Armand, Nathalie A Johnson, Pauline Brice, John Radford, Vincent Ribrag, Daniel Molin, Theodoros P Vassilakopoulos, Akihiro Tomita, Bastian von Tresckow, Margaret A Shipp, Yinghua Zhang, Alejandro D Ricart, Arun Balakumaran, Craig H Moskowitz
Purpose Hodgkin Reed-Sternberg cells harbor alterations in chromosome 9p24.1, leading to overexpression of programmed death-ligand 1 (PD-L1) and PD-L2. Pembrolizumab, a programmed death 1-blocking antibody, demonstrated a high overall response rate (ORR) in patients with relapsed or refractory classic Hodgkin lymphoma (rrHL) in phase I testing. Methods KEYNOTE-087 ( ClinicalTrials.gov identifier, NCT02453594) was a single-arm phase II study of pembrolizumab in three cohorts of patients with rrHL, defined on the basis of lymphoma progression after (1) autologous stem cell transplantation (ASCT) and subsequent brentuximab vedotin (BV); (2) salvage chemotherapy and BV, and thus, ineligible for ASCT because of chemoresistant disease; and (3) ASCT, but without BV after transplantation...
April 25, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28438889/fda-approval-summary-nivolumab-for-the-treatment-of-relapsed-or-progressive-classical-hodgkin-lymphoma
#2
Yvette L Kasamon, R Angelo de Claro, Yaping Wang, Yuan Li Shen, Ann T Farrell, Richard Pazdur
On May 17, 2016, after an expedited priority review, the U.S. Food and Drug Administration granted accelerated approval to nivolumab for the treatment of patients with classical Hodgkin lymphoma (cHL) that has relapsed or progressed after autologous hematopoietic stem cell transplantation (HSCT) and post-transplantation brentuximab vedotin (BV). Nivolumab in cHL had been granted breakthrough therapy designation. Accelerated approval was based on two single-arm, multicenter trials in adults with cHL. In 95 patients with relapsed or progressive cHL after autologous HSCT and post-transplantation BV, nivolumab, dosed at 3 mg/kg intravenously every 2 weeks, produced a 65% (95% confidence interval: 55%-75%) objective response rate (58% partial remission, 7% complete remission)...
April 24, 2017: Oncologist
https://www.readbyqxmd.com/read/28427526/potential-application-and-prevalence-of-the-cd30-ki-1-antigen-among-solid-tumors-a-focus-review-of-the-literature
#3
REVIEW
Garrett K Berger, Kevin Gee, Cassandra Votruba, Ali McBride, Faiz Anwer
BACKGROUND: CD30 (Ki-1) is a cell membrane protein derived from the tumor necrosis factor (TNF) receptor family. The CD30 antigen has been associated primarily with Hodgkin lymphoma (HL) and systemic anaplastic large cell lymphoma (sALCL). Brentuximab vedotin (BV) is an antibody-drug conjugate targeting the CD30 antigen. FDA approval for BV includes relapsed and refractory HL and sALCL. The CD30 antigen also has been identified in many solid tumors, predominantly of germ cell origins and early clinical data is promising...
May 2017: Critical Reviews in Oncology/hematology
https://www.readbyqxmd.com/read/28413663/breast-implant-associated-anaplastic-large-cell-lymphoma-and-the-role-of-brentuximab-vedotin-sgn-35-therapy-a-case-report-and-review-of-the-literature
#4
Kristin Richardson, Taha Alrifai, Kelly Grant-Szymanski, George J Kouris, Parameswaran Venugopal, Brett Mahon, Reem Karmali
Breast implant-associated (BIA) anaplastic large-cell lymphoma (ALCL) is a rare disease, comprising a small percentage of all non-Hodgkin lymphomas (NHLs), reportedly 2-3%. There is currently no established standard approach to the treatment of BIA ALCL. The first case on the development of ALCL in the presence of a breast implant was reported in 1997 and the association was first identified by the Food and Drug Administration in 2011. We herein describe a case of BIA ALCL in a patient with a previous history of breast cancer and breast reconstruction who presented with hardening of her breast implant...
April 2017: Molecular and Clinical Oncology
https://www.readbyqxmd.com/read/28400633/new-targeted-treatments-for-cutaneous-t-cell-lymphomas
#5
Martine Bagot
Cutaneous T-cell lymphomas (CTCLs) represent a group of rare and heterogeneous diseases that are very difficult to treat at advanced stages. The development of monoclonal antibodies is a new hope for the treatment of these diseases. Alemtuzumab (Campath) is a humanized IgG1 kappa monoclonal antibody specific for CD52, an antigen expressed by most T and B lymphocytes. Alemtuzumab may frequently induce long-term remissions in patients with Sezary syndrome but high-dose treatments lead to severe cytopenia, immune depletion, and opportunistic infections...
March 2017: Indian Journal of Dermatology
https://www.readbyqxmd.com/read/28388844/effects-of-drug-antibody-ratio-dar-on-pharmacokinetics-biodistribution-efficacy-and-tolerability-of-antibody-maytansinoid-conjugates
#6
Xiuxia Sun, Jose F Ponte, Nicholas Yoder, Rassol Laleau, Jennifer Coccia, Leanne Lanieri, Qifeng Qiu, Rui Wu, Erica Hong, Megan Bogalhas, Lintao Wang, Ling Dong, Yulius Setiady, Erin Maloney, Olga Ab, Xiaoyan Zhang, Jan Pinkas, Thomas Keating, Ravi V J Chari, Hans Erickson, John M Lambert
Antibody-drug conjugates (ADCs) are being actively pursued as a treatment option for cancer following the regulatory approval of brentuximab vedotin (Adcetris®) and ado-trastuzumab emtansine (Kadcyla®). ADCs consist of a cytotoxic agent conjugated to a targeting antibody through a linker. The two approved ADCs (and most ADCs now in the clinic that use a microtubule disrupting agent as the payload) are heterogeneous conjugates with an average drug to antibody ratio (DAR) of 3-4 (potentially ranging from 0-8 for individual species)...
April 7, 2017: Bioconjugate Chemistry
https://www.readbyqxmd.com/read/28361465/antibody-drug-conjugates-adcs-for-personalized-treatment-of-solid-tumors-a-review
#7
REVIEW
John M Lambert, Charles Q Morris
Attaching a cytotoxic "payload" to an antibody to form an antibody-drug conjugate (ADC) provides a mechanism for selective delivery of the cytotoxic agent to cancer cells via the specific binding of the antibody to cancer-selective cell surface molecules. The first ADC to receive marketing authorization was gemtuzumab ozogamicin, which comprises an anti-CD33 antibody conjugated to a highly potent DNA-targeting antibiotic, calicheamicin, approved in 2000 for treating acute myeloid leukemia. It was withdrawn from the US market in 2010 following an unsuccessful confirmatory trial...
March 30, 2017: Advances in Therapy
https://www.readbyqxmd.com/read/28359170/immunotherapy-for-the-treatment-of-hodgkin-lymphoma
#8
Eva M Donato, Miguel Fernández-Zarzoso, Javier De La Rubia
Most patients with Hodgkin lymphoma (HL) enjoy durable remissions following front-line treatment but 30% of patients are refractory or relapse after first line therapy. Salvage chemotherapy followed by autologous stem cell transplantation (ASCT) can cure an additional 50-55% of relapsing patients but new treatments are needed for patients with HL who are refractory or relapse after ASCT. Immunotherapy has emerged as a promising treatment for the management of these patients. The availability of the anti-CD30 antibody brentuximab vedotin and new targeted drugs such as immune checkpoint inhibitors, show promising clinical activity in patients with HL and are important milestones for the management of patients with HL particularly for those who have progressed after standard initial therapy and ASCT...
April 12, 2017: Expert Review of Hematology
https://www.readbyqxmd.com/read/28351183/bendamustine-as-a-bridge-to-allogeneic-transplant-in-relapsed-refractory-hodgkin-lymphoma-patients-who-failed-salvage-brentuximab-vedotin-postautologous-peripheral-blood-stem-cell-transplantation
#9
Jean El Cheikh, Radwan Massoud, Basel Haffar, Elie Fares, Rami Mahfouz, Tamima Jisr, Mohamed A Kharfan-Dabaja, Anas Mougharbel, Ali Youssef, Ali Bazarbachi, Ahmad Ibrahim
No abstract text is available yet for this article.
March 28, 2017: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/28340883/novel-agents-in-the-treatment-of-relapsed-or-refractory-peripheral-t-cell-lymphoma
#10
REVIEW
Enrica Marchi, Alexander G Raufi, Owen A O'Connor
Peripheral T-cell lymphomas (PTCL) are a heterogeneous group of mature T-cell malignancies associated with exceptionally poor prognoses. Currently, chemotherapy remains the standard of care, but outcomes are suboptimal, with 5-year survival rates ranging from 15% to 25%. In recent years, several novel agents, including pralatrexate, romidepsin, belinostat, and brentuximab vedotin, have been approved for the treatment of relapsed/refractory PTCL. In addition, numerous other therapies with different mechanisms of action and targets are currently under investigation...
April 2017: Hematology/oncology Clinics of North America
https://www.readbyqxmd.com/read/28340874/management-of-anaplastic-large-cell-lymphoma
#11
REVIEW
Dai Chihara, Michelle A Fanale
Anaplastic large cell lymphoma (ALCL) is one of the most common peripheral T-cell lymphomas, and the incidence is higher in blacks than non-Hispanic whites. ALK-positive and ALK-negative ALCL are distinct subtypes that have different characteristics and clinical outcomes. Breast implant-associated ALCL is a rare lymphoma that has a good survival outcome, and a recent study showed that total capsulectomy is essential for treatment. Brentuximab vedotin (BV) is a standard treatment for relapsed/refractory ALCL...
April 2017: Hematology/oncology Clinics of North America
https://www.readbyqxmd.com/read/28327905/phase-ii-study-of-idelalisib-a-selective-inhibitor-of-pi3k%C3%AE-for-relapsed-refractory-classical-hodgkin-lymphoma
#12
A K Gopal, M A Fanale, C H Moskowitz, A R Shustov, S Mitra, W Ye, A Younes, A J Moskowitz
Background: The phosphatidylinositol-3-kinase delta (PI3Kδ) inhibitor idelalisib has been shown to block downstream intracellular signaling, reduce the production of prosurvival chemokines and induce apoptosis in classical Hodgkin lymphoma (HL) cell lines. It has also been shown to inhibit regulatory T cells and myeloid-derived suppressor cells in other tumor models. We hypothesized that inhibiting PI3Kδ would have both direct and indirect antitumor effects by directly targeting the malignant cells as well as modulating the inflammatory microenvironment...
January 24, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/28320689/use-of-the-total-cancer-care-system-to-enrich-screening-for-cd30-positive-solid-tumors-for-patient-enrollment-into-a-brentuximab-vedotin-clinical-trial-a-pilot-study-to-evaluate-feasibility
#13
Bin Li, Steven A Eschrich, Anders Berglund, Melissa Mitchell, David Fenstermacher, Hadi Danaee, Hongyue Dai, Daniel Sullivan, William L Trepicchio, William S Dalton
BACKGROUND: One approach to identify patients who meet specific eligibility criteria for target-based clinical trials is to use patient and tumor registries to prescreen patient populations. OBJECTIVE: Here we demonstrate that the Total Cancer Care (TCC) Protocol, an ongoing, observational study, may provide a solution for rapidly identifying patients with CD30-positive tumors eligible for CD30-targeted therapies such as brentuximab vedotin. METHODS: The TCC patient gene expression profiling database was retrospectively screened for CD30 gene expression determined using HuRSTA-2a520709 Affymetrix arrays (GPL15048)...
March 20, 2017: JMIR Research Protocols
https://www.readbyqxmd.com/read/28318345/novel-agents-in-classical-hodgkin-lymphoma
#14
Sven Borchmann, Bastian von Tresckow
Classical Hodgkin lymphoma (cHL) is the most common hematological malignancy in young adults and can be cured in most cases. However, relapsed and refractory Hodgkin lymphoma, certain patient groups, such as elderly patients, and toxicity of first-line treatment still pose significant challenges. Consequently, new treatment options are needed. Recently, many new treatment concepts have been evaluated in clinical trials. Targeted drug-antibody conjugates and immune checkpoint inhibitors have decisively changed treatment approaches...
March 20, 2017: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/28303026/strategies-and-challenges-for-the-next-generation-of-antibody-drug-conjugates
#15
REVIEW
Alain Beck, Liliane Goetsch, Charles Dumontet, Nathalie Corvaïa
Antibody-drug conjugates (ADCs) are one of the fastest growing classes of oncology therapeutics. After half a century of research, the approvals of brentuximab vedotin (in 2011) and trastuzumab emtansine (in 2013) have paved the way for ongoing clinical trials that are evaluating more than 60 further ADC candidates. The limited success of first-generation ADCs (developed in the early 2000s) informed strategies to bring second-generation ADCs to the market, which have higher levels of cytotoxic drug conjugation, lower levels of naked antibodies and more-stable linkers between the drug and the antibody...
May 2017: Nature Reviews. Drug Discovery
https://www.readbyqxmd.com/read/28278730/is-cd30-a-predictive-biomarker-for-brentuximab-vedotin
#16
Robert Chen
No abstract text is available yet for this article.
February 6, 2017: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/28273193/-drug-therapy-of-lymphomas
#17
Lajos Gergely
The therapy of lymphomas has undergone a major expansion during the last decade. Novel therapeutic targets have appeared beyond classical chemotherapeutic combinations. These novel drugs have very pronounced action across lymphoma types, and their toxicity profile is usually better tolerable compared to standard chemotherapies. These new therapies are enabling us to offer treatment to those patients who have refractory disease, and we had no option to treat them before these drugs. The author describes several new therapeutic options...
March 8, 2017: Magyar Onkologia
https://www.readbyqxmd.com/read/28271282/characterization-of-the-peripheral-neuropathy-associated-with-brentuximab-vedotin-treatment-of-mycosis-fungoides-and-s%C3%A3-zary-syndrome
#18
Zachary A Corbin, Annie Nguyen-Lin, Shufeng Li, Ziba Rahbar, Mahkam Tavallaee, Hannes Vogel, Katrin A Salva, Gary S Wood, Youn H Kim, Seema Nagpal
Chemotherapy-induced peripheral neuropathy (CIPN) is common, frequently limits chemotherapy dosing, and negatively impacts quality of life. The National Cancer Institute Common Toxicity Criteria for Adverse Events (CTCAE), version 4.0, and the Total Neuropathy Score clinical version (TNSc) are both validated scores to quantify peripheral neuropathy (PN), with the TNSc being more sensitive to clinical changes. Mycosis fungoides and Sézary syndrome (MF/SS) are characterized by a chronic course, where current therapies are generally non-curative and treatment toxicities have the potential for significant lasting effects...
March 7, 2017: Journal of Neuro-oncology
https://www.readbyqxmd.com/read/28270727/economic-evaluation-of-brentuximab-vedotin-for-persistent-hodgkin-lymphoma
#19
V Babashov, M A Begen, J Mangel, G S Zaric
BACKGROUND: We conducted a cost-effectiveness analysis of brentuximab vedotin for the treatment of relapsed and refractory Hodgkin lymphoma (hl) in the post-autologous stem-cell transplantation (asct) failure period, from the perspective of the Canadian health care payer. METHODS: We developed a decision-analytic model to simulate lifetime costs and benefits of brentuximab vedotin compared with best supportive care for the treatment of patients with hl after failure of asct...
February 2017: Current Oncology
https://www.readbyqxmd.com/read/28267244/a-multicenter-phase-ii-study-of-nivolumab-in-japanese-patients-with-relapsed-or-refractory-classical-hodgkin-lymphoma
#20
Dai Maruyama, Kiyohiko Hatake, Tomohiro Kinoshita, Noriko Fukuhara, Ilseung Choi, Masafumi Taniwaki, Kiyoshi Ando, Yasuhito Terui, Yusuke Higuchi, Yasushi Onishi, Yasunobu Abe, Tsutomu Kobayashi, Yukari Shirasugi, Kensei Tobinai
Overexpression of programmed death-1 (PD-1) ligands contributes to an immunosuppressive microenvironment. Nivolumab is a PD-1-blocking antibody that inhibits the PD-1 pathway and showed good efficacy in several types of malignancy. This phase II study examined the efficacy and safety of nivolumab in 17 Japanese patients with refractory/relapsed classical Hodgkin lymphoma previously treated with brentuximab vedotin. Sixteen patients were included in efficacy analyses and 17 in safety analyses. The primary endpoint was the centrally assessed objective response rate (ORR)...
March 7, 2017: Cancer Science
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