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https://www.readbyqxmd.com/read/28805662/clinical-and-immunological-responses-after-cd30-specific-chimeric-antigen-receptor-redirected-lymphocytes
#1
Carlos A Ramos, Brandon Ballard, Huimin Zhang, Olga Dakhova, Adrian P Gee, Zhuyong Mei, Mrinalini Bilgi, Meng-Fen Wu, Hao Liu, Bambi Grilley, Catherine M Bollard, Bill H Chang, Cliona M Rooney, Malcolm K Brenner, Helen E Heslop, Gianpietro Dotti, Barbara Savoldo
BACKGROUND: Targeting CD30 with monoclonal antibodies in Hodgkin lymphoma (HL) and anaplastic large cell lymphoma (ALCL) has had profound clinical success. However, adverse events, mainly mediated by the toxin component of the conjugated antibodies, cause treatment discontinuation in many patients. Targeting CD30 with T cells expressing a CD30-specific chimeric antigen receptor (CAR) may reduce the side effects and augment antitumor activity. METHODS: We conducted a phase I dose escalation study in which 9 patients with relapsed/refractory HL or ALCL were infused with autologous T cells that were gene-modified with a retroviral vector to express the CD30-specific CAR (CD30...
August 14, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28805086/brentuximab-vedotin-therapy-for-cd30-positive-cutaneous-t-cell-lymphoma-a-targeted-approach-to-management
#2
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
#3
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
#4
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
#5
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
#6
REVIEW
Pamela A Trail, Gene M Dubowchik, Timothy 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
#7
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
#8
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...
July 20, 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
#9
Joseph M Connors, Stephen M Ansell, Michelle Fanale, Steven I Park, Anas Younes
No abstract text is available yet for this article.
July 21, 2017: Blood
https://www.readbyqxmd.com/read/28708333/conversion-from-calcineurin-inhibitors-to-mtor-inhibitors-as-primary-immunosuppressive-drugs-in-pediatric-heart-transplantation
#10
Alfred Asante-Korang, Jennifer Carapellucci, Diane Krasnopero, Abigail Doyle, Brian Brown, Ernest Amankwah
There are only a few reports of successful use of mammalian target of rapamycin (mTORI) as primary immunosuppression in pediatric heart transplantation. Compared to calcineurin inhibitors, mTORI have less side effects, especially nephrotoxicity, infections, and malignancies. A retrospective study was conducted at our institution of all 170 heart transplants from 1995 to 2015. Nineteen patients were switched from tacrolimus (n=15) or cyclosporin (n=4) to everolimus (n=4) or sirolimus (n=15) due to nephrotoxicity (n=5), malignancy (n=8), EBV viremia/reactive plasmacytic changes (n=5), and immune hemolytic anemia (n=1)...
July 14, 2017: Clinical Transplantation
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
#11
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
#12
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
#13
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...
July 10, 2017: Expert Review of Hematology
https://www.readbyqxmd.com/read/28649848/mogamulizumab-for-the-treatment-of-t-cell-lymphoma
#14
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
#15
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
#16
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
#17
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/28634100/anaphylactic-shock-due-to-brentuximab-vendotin-confirmed-by-skin-test-and-in%C3%A2-vitro-tests
#18
Blanca Noguerado-Mellado, Patricia Rojas-Pérez-Ezquerra, Mercedes Sáenz de Santa María García, Gabriela Rodriguez-Macías, Pilar Tornero, Borja Bartolomé
No abstract text is available yet for this article.
June 17, 2017: Journal of Allergy and Clinical Immunology in Practice
https://www.readbyqxmd.com/read/28632694/multiorgan-involvement-of-chemotherapy-induced-sarcoidosis-mimicking-progression-of-lymphoma-on-fdg-pet-ct
#19
Prateek Sanan, Yang Lu
A 35-year-old woman with biopsy-proven recurrent Hodgkin lymphoma in the neck lymph nodes received salvage chemotherapy of brentuximab/insulin growth factor-methotrexate. Although the patient continued doing well clinically with no constitutional symptoms or significant laboratory abnormalities following the second recurrence, subsequent FDG PET CT examinations over the next 2 years revealed multiple new FDG-avid foci including lymph nodes above/below the diaphragm, liver, spleen, lungs, and bone. An alternate diagnosis of chemotherapy-induced sarcoidosis was suggested and confirmed on both bone marrow and right inguinal node biopsy...
September 2017: Clinical Nuclear Medicine
https://www.readbyqxmd.com/read/28631737/haematological-cancer-brentuximab-vedotin-a-new-standard-for-cutaneous-t-cell-lymphoma
#20
David Killock
No abstract text is available yet for this article.
August 2017: Nature Reviews. Clinical Oncology
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