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brentuximab vedotin

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https://www.readbyqxmd.com/read/28885612/understanding-cd30-biology-and-therapeutic-targeting-a-historical-perspective-providing-insight-into-future-directions
#1
REVIEW
C A van der Weyden, S A Pileri, A L Feldman, J Whisstock, H M Prince
CD30 is a member of the tumor necrosis factor receptor superfamily. It is characteristically expressed in certain hematopoietic malignancies, including anaplastic large cell lymphoma and Hodgkin lymphoma, among others. The variable expression of CD30 on both normal and malignant lymphoid cells has focused research efforts on understanding the pathogenesis of CD30 upregulation, its contribution to lymphomagenesis through anti-apoptotic mechanisms, and its effect on cell survival. Given the restriction of CD30 to certain tumor types, the logical extension of this has been to attempt to exploit it as a therapeutic target...
September 8, 2017: Blood Cancer Journal
https://www.readbyqxmd.com/read/28874350/prognostic-significance-of-baseline-metabolic-tumor-volume-in-relapsed-and-refractory-hodgkin-lymphoma
#2
Alison J Moskowitz, Heiko Schöder, Somali Gavane, Katie L Thoren, Martin Fleisher, Joachim Yahalom, Susan J McCall, Briana R Cadzin, Stephanie Y Fox, John Gerecitano, Ravinder Grewal, Paul A Hamlin, Steven M Horwitz, Anita Kumar, Matthew Matasar, Andy Ni, Ariela Noy, M Lia Palomba, Miguel-Angel Perales, Carol S Portlock, Craig Sauter, David Straus, Anas Younes, Andrew D Zelenetz, Craig H Moskowitz
Identification of prognostic factors for patients with relapsed or refractory (rel/ref) Hodgkin lymphoma (HL) is essential for optimizing therapy with risk-adapted approaches. In our phase II study of PET-adapted salvage therapy with brentuximab vedotin (BV) and augmented ifosfamide, carboplatin, etoposide (augICE) we assessed clinical factors, quantitative PET assessments, and cytokines/chemokine values. Transplant-eligible patients with rel/ref HL received 2 (cohort 1) or 3 (cohort 2) cycles of weekly BV; PET-negative (Deauville ≤ 2) patients proceeded to autologous stem cell transplant (ASCT) while PET-positive patients received augICE before ASCT...
September 5, 2017: Blood
https://www.readbyqxmd.com/read/28857136/results-of-a-multicentre-uk-wide-retrospective-study-evaluating-the-efficacy-of-brentuximab-vedotin-in-relapsed-refractory-classical-hodgkin-lymphoma-in-the-transplant-naive-setting
#3
Toby A Eyre, Elizabeth H Phillips, Kim M Linton, Shireen Kassam, Adam Gibb, Suzanne Allibone, John Radford, Karl Peggs, Cathy Burton, Gillian Stewart, Rifca LeDieu, Catherine Booth, Wendy L Osborne, Fiona Miall, David W Eyre, Kirit M Ardeshna, Graham P Collins
Relapsed or refractory classical Hodgkin lymphoma (cHL) is associated with a poor outcome when standard chemotherapy fails. Brentuximab vedotin (BV) is an anti-CD30 monoclonal antibody-drug conjugate licensed for use at relapse after autologous stem cell transplant (ASCT) or following two prior therapies in those unsuitable for ASCT. There are limited data assessing the ability of BV to enable curative SCT. We performed a UK-wide retrospective study of 99 SCT-naïve relapsed/refractory cHL. All had received 2 prior lines and were deemed fit for transplant but had an insufficient remission to proceed...
August 31, 2017: British Journal of Haematology
https://www.readbyqxmd.com/read/28805086/brentuximab-vedotin-therapy-for-cd30-positive-cutaneous-t-cell-lymphoma-a-targeted-approach-to-management
#4
Julia J Scarisbrick
CD30-positive primary cutaneous T-cell lymphoma (CTCL) includes mycosis fungoides, anaplastic large-cell lymphoma and lymphomatoid papulosis type A. Brentuximab vedotin (BV) consists of an antibody targeting CD30 with a protease-cleavable linker to vedotin. CD30 binding allows internalization of BV inducing cell-cycle arrest and apoptosis. Response rates >75% with manageable adverse effects in refractory Hodgkin lymphoma and systemic anaplastic large-cell lymphoma led to accelerated approval for both. Phase II studies in CD30-expressing CTCL followed and showed similar efficacy, which was ratified in a Phase III trial of BV versus physician's choice (methotrexate or bexarotene) showing significant improved responses without increase in severe adverse effects although peripheral neuropathy is frequent...
August 14, 2017: Future Oncology
https://www.readbyqxmd.com/read/28775121/italian-real-life-experience-with-brentuximab-vedotin-results-of-a-large-observational-study-on-40-relapsed-refractory-systemic-anaplastic-large-cell-lymphoma
#5
Alessandro Broccoli, Cinzia Pellegrini, Alice Di Rocco, Benedetta Puccini, Caterina Patti, Guido Gini, Donato Mannina, Monica Tani, Chiara Rusconi, Alessandra Romano, Anna Vanazzi, Barbara Botto, Carmelo Carlo-Stella, Stefan Hohaus, Pellegrino Musto, Patrizio Mazza, Stefano Molica, Paolo Corradini, Angelo Fama, Francesco Gaudio, Michele Merli, Angela Gravetti, Giuseppe Gritti, Annalisa Arcari, Patrizia Tosi, Anna Marina Liberati, Antonello Pinto, Vincenzo Pavone, Filippo Gherlinzoni, Virginia Naso, Stefano Volpetti, Livio Trentin, Maria Cecilia Goldaniga, Maurizio Bonfichi, Amalia De Renzo, Corrado Schiavotto, Michele Spina, Sergio Storti, Angelo Michele Carella, Vittorio Stefoni, Lisa Argnani, Pier Luigi Zinzani
From November 2012 to July 2014, brentuximab vedotin was available in Italy for patients with relapsed systemic anaplastic large cell lymphoma outside a clinical trial context according to the national law 648/96. A large Italian observational retrospective study was conducted on the use of brentuximab vedotin in the everyday clinical practice to check if clinical trial results are confirmed even in a real life context. Primary endpoint was the best response; secondary endpoints were the overall response rate at the end of the treatment, duration of response, survival and the safety profile...
August 3, 2017: Haematologica
https://www.readbyqxmd.com/read/28770285/-treatment-of-mycosis-fungoides-and-s%C3%A3-zary-syndrome
#6
REVIEW
J P Nicolay, C Assaf
Adequate therapeutic management of cutaneous T-cell lymphoma (CTCL) requires the identification of the exact CTCL stage and entity within the current WHO classification. There is no curative therapy for CTCL yet, so that treatment currently aims at improving symptoms and quality of life as well as reducing relapse rates. The treatment has to be stage-adapted. Therapeutic options comprise skin-directed as well as systemic treatment. In early stages, phototherapy and local steroids are the first-line therapeutic options...
August 2, 2017: Der Hautarzt; Zeitschrift Für Dermatologie, Venerologie, und Verwandte Gebiete
https://www.readbyqxmd.com/read/28762479/brentuximab-vedotin-in-cd30-primary-cutaneous-t-cell-lymphomas-a-review-and-analysis-of-existing-data
#7
Tyler H Enos, Lawrence S Feigenbaum, Heather W Wickless
BACKGROUND: The utility of brentuximab vedotin (BV) in CD30(+) systemic lymphomas is established, however evidence for treating primary cutaneous lymphoma remains limited. This study aimed to evaluate BV in treating CD30(+) transformed mycosis fungoides (MF) and primary cutaneous anaplastic large cell lymphoma (PC-ALCL). METHODS: A literature review was conducted, and we analyzed data from published trials and case reports obtained via search of Ovid-MEDLINE(®) and PubMed databases...
August 1, 2017: International Journal of Dermatology
https://www.readbyqxmd.com/read/28757155/antibody-drug-conjugates-for-treatment-of-breast-cancer-novel-targets-and-diverse-approaches-in-adc-design
#8
REVIEW
Pamela A Trail, Gene M Dubowchik, Timothy B Lowinger
Breast cancer is a heterogeneous group of malignancies with a spectrum of molecular subtypes, pathologies and outcomes that together comprise the most common non-cutaneous cancer in women. Currently, over 80% of breast cancer patients are diagnosed at relatively early stages of disease where there are encouraging data on outcomes and long term survival. However, there is currently no curative option for those patients with metastatic disease and there is a substantial medical need to identify effective and safe treatment options for these patients...
July 27, 2017: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28741467/status-quo-in-antibody-drug-conjugates-can-glyco-enzymes-solve-the-current-challenges
#9
Florentina Kubizek, Britta Eggenreich, Oliver Spadiut
Over the last years, a novel class of anti-cancer drugs named antibody-drug conjugates (ADCs) has been developed. Due to their limited off-target toxicity but highly potent cytotoxicity at tumor sites, ADCs have proven to be a good alternative to ordinary cancer treatment, such as chemotherapy or combination therapy. Numerous enhancements in antibody-drug engineering led to highly potent tumor targeting drugs with a wide therapeutic window. Two ADCs (Brentuximab vedotin and Trastuzumab emtansine) are already on the market and many others in clinical trials...
July 24, 2017: Protein and Peptide Letters
https://www.readbyqxmd.com/read/28735072/long-term-outcomes-of-adults-with-first-relapsed-refractory-systemic-anaplastic-large-cell-lymphoma-in-the%C3%A2-pre-brentuximab-vedotin-era-a-lysa-sfgm-tc-study
#10
Alexandre Morel, Josette Brière, Laurence Lamant, Michaël Loschi, Corinne Haioun, Richard Delarue, Olivier Tournilhac, Emmanuel Bachy, Anne Sonet, Sandy Amorim, Camille Laurent, Philippe Gaulard, Hervé Tilly, David Sibon
BACKGROUND: Long-term outcomes of adults with first-relapsed/refractory (R/R) systemic anaplastic large-cell lymphoma (ALCL) are not definitively established and should be evaluated. PATIENTS AND METHODS: We previously published the long-term outcomes of adults with ALCL initially treated with polychemotherapy in LYmphoma Study Association (LYSA) prospective clinical trials conducted during the pre-brentuximab vedotin era. Herein, we report the long-term outcomes of those patients after the first-relapsed/refractory (R/R) events...
September 2017: European Journal of Cancer
https://www.readbyqxmd.com/read/28733323/five-year-follow-up-of-brentuximab-vedotin-combined-with-abvd-or-avd-for-advanced-stage-classical-hodgkin-lymphoma
#11
LETTER
Joseph M Connors, Stephen M Ansell, Michelle Fanale, Steven I Park, Anas Younes
No abstract text is available yet for this article.
September 14, 2017: Blood
https://www.readbyqxmd.com/read/28703284/brentuximab-vedotin-in-cd30-cutaneous-lymphoma-how-do-we-treat-how-shall-we-treat-a-review-of-the-literature
#12
REVIEW
R Stranzenbach, E Dippel, M Schlaak, R Stadler
Brentuximab vedotin is an antibody-drug conjugate that brings the antimicrotubule agent monomethyl auristatin E into CD30-expressing cells. Some prior studies could demonstrate good efficacy in cutaneous lymphomas. The standard therapeutic scheme is 1.8mg/kg every 3 weeks. Background of this work is the fact that cutaneous lymphoma has a different pathophysiology, and a dynamic other than systemic lymphoma. The objectives of this review were to get an overview of the currently used therapeutic regimen, and to check whether dose reduction or modified time intervals could benefit in a similar activity with less toxicity...
July 13, 2017: British Journal of Dermatology
https://www.readbyqxmd.com/read/28701859/advances-in-the-pathophysiology-and-treatment-of-relapsed-refractory-hodgkin-s-lymphoma-with-an-emphasis-on-targeted-therapies-and-transplantation-strategies
#13
Theodoros Karantanos, Ioannis Politikos, Vassiliki A Boussiotis
Hodgkin's lymphoma (HL) is highly curable with first-line therapy. However, a minority of patients present with refractory disease or experience relapse after completion of frontline treatment. These patients are treated with salvage chemotherapy followed by autologous stem cell transplantation (ASCT), which remains the standard of care with curative potential for refractory or relapsed HL. Nevertheless, a significant percentage of such patients will progress after ASCT, and allogeneic hematopoietic stem cell transplantation remains the only curative approach in that setting...
2017: Blood and Lymphatic Cancer: Targets and Therapy
https://www.readbyqxmd.com/read/28665214/the-evolving-role-of-targeted-drugs-in-the-treatment-of-hodgkin-lymphoma
#14
Dennis A Eichenauer, Andreas Engert
Hodgkin lymphoma (HL) is a B-cell-derived malignancy mostly affecting young adults. More than 80% of patients are cured after stage-adapted first-line treatment with chemotherapy and/or radiotherapy. About 50% of patients with disease recurrence achieve long-term remission with second-line treatment consisting of high-dose chemotherapy and autologous stem cell transplantation. However, HL treatment is often associated with acute toxicity and in part life-threatening late effects. Implementing targeted drugs may reduce toxicity and potentially further optimize efficacy...
September 2017: Expert Review of Hematology
https://www.readbyqxmd.com/read/28649848/mogamulizumab-for-the-treatment-of-t-cell-lymphoma
#15
Shinichi Makita, Kensei Tobinai
T-cell lymphoma is a relatively rare hematologic malignancy that accounts for 10-20% of non-Hodgkin lymphomas. Treatment strategies for T-cell lymphomas are different from that for B-cell lymphomas and have poor prognoses. Among various subtypes of T-cell lymphomas, adult T-cell leukemia-lymphoma (ATL) has the worst prognosis. To achieve further improvement in the treatment outcome of T-cell lymphomas, several novel agents such as brentuximab vedotin, lenalidomide, romidepsin, and pralatrexate are actively being studied...
September 2017: Expert Opinion on Biological Therapy
https://www.readbyqxmd.com/read/28646408/a-mechanism-based-pk-pd-model-for-hematological-toxicities-induced-by-antibody-drug-conjugates
#16
Sihem Ait-Oudhia, Weiyan Zhang, Donald E Mager
Antibody-drug conjugates (ADCs) are complex drug platforms composed of monoclonal antibodies (mAbs) conjugated to potent cytotoxic drugs (payloads) via chemical linkers, enabling selective payload delivery to neoplastic cells, resulting in improved efficacy and reduced toxicity. Brentuximab vedotin (Adcetris®, SGN-35) and adotrastuzumab emtansine (Kadcyla®, T-DM1) are the two FDA-approved and commercially available ADCs, and both drugs exhibit ADC-related thrombocytopenia and neutropenia. A pharmacokinetic/pharmacodynamic (PK/PD) model for ADCs was developed to identify the analyte from each ADC that is most associated with the observed hematopoietic toxicities and to determine the role of the apparent in vivo payload release rate on the severity of thrombocytopenia and neutropenia...
June 23, 2017: AAPS Journal
https://www.readbyqxmd.com/read/28640385/cost-effectiveness-analysis-of-consolidation-with-brentuximab-vedotin-for-high-risk-hodgkin-lymphoma-after-autologous-stem-cell-transplantation
#17
Lucy Hui, Gottfried von Keudell, Rong Wang, Amer M Zeidan, Steven D Gore, Xiaomei Ma, Amy J Davidoff, Scott F Huntington
BACKGROUND: In a recent randomized, placebo-controlled trial, consolidation treatment with brentuximab vedotin (BV) decreased the risk of Hodgkin lymphoma (HL) progression after autologous stem cell transplantation (ASCT). However, the impact of BV consolidation on overall survival, quality of life, and health care costs remain unclear. METHODS: A Markov decision-analytic model was constructed to measure the costs and clinical outcomes for BV consolidation therapy compared with active surveillance in a cohort of patients aged 33 years who were at risk for HL relapse after ASCT...
June 22, 2017: Cancer
https://www.readbyqxmd.com/read/28638848/cytomegalovirus-infection-with-retinitis-after-brentuximab-vedotin-treatment-for-cd30-lymphoma
#18
Jean-Jacques Tudesq, Laure Vincent, Julie Lebrun, Yosr Hicheri, Ludovic Gabellier, Timothé Busetto, Corinne Merle, Nathalie Fegueux, Patrice Ceballos, Philippe Quittet, Robert Navarro, Dominique Hillaire-Buys, Guillaume Cartron
Brentuximab vedotin is an antibody-conjugated chemotherapy targeting CD30 indicated in treatment of several lymphomas. We report the first 3 cases of cytomegalovirus severe infections with retinitis following this treatment. Evolution was favorable, but relapse occurred after treatment rechallenge. We suggest vigilance about cytomegalovirus in patients treated with brentuximab vedotin.
2017: Open Forum Infectious Diseases
https://www.readbyqxmd.com/read/28631737/haematological-cancer-brentuximab-vedotin-a-new-standard-for-cutaneous-t-cell-lymphoma
#19
David Killock
No abstract text is available yet for this article.
August 2017: Nature Reviews. Clinical Oncology
https://www.readbyqxmd.com/read/28600132/brentuximab-vedotin-or-physician-s-choice-in-cd30-positive-cutaneous-t-cell-lymphoma-alcanza-an-international-open-label-randomised-phase-3-multicentre-trial
#20
H Miles Prince, Youn H Kim, Steven M Horwitz, Reinhard Dummer, Julia Scarisbrick, Pietro Quaglino, Pier Luigi Zinzani, Pascal Wolter, Jose A Sanches, Pablo L Ortiz-Romero, Oleg E Akilov, Larisa Geskin, Judith Trotman, Kerry Taylor, Stephane Dalle, Michael Weichenthal, Jan Walewski, David Fisher, Brigitte Dréno, Rudolf Stadler, Tatyana Feldman, Timothy M Kuzel, Yinghui Wang, Maria Corinna Palanca-Wessels, Erin Zagadailov, William L Trepicchio, Wenwen Zhang, Hui-Min Lin, Yi Liu, Dirk Huebner, Meredith Little, Sean Whittaker, Madeleine Duvic
BACKGROUND: Cutaneous T-cell lymphomas are rare, generally incurable, and associated with reduced quality of life. Present systemic therapies rarely provide reliable and durable responses. We aimed to assess efficacy and safety of brentuximab vedotin versus conventional therapy for previously treated patients with CD30-positive cutaneous T-cell lymphomas. METHODS: In this international, open-label, randomised, phase 3, multicentre trial, we enrolled adult patients with CD30-positive mycosis fungoides or primary cutaneous anaplastic large-cell lymphoma who had been previously treated...
August 5, 2017: Lancet
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