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https://www.readbyqxmd.com/read/28646408/a-mechanism-based-pk-pd-model-for-hematological-toxicities-induced-by-antibody-drug-conjugates
#1
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
#2
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
#3
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
#4
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
#5
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...
June 19, 2017: Clinical Nuclear Medicine
https://www.readbyqxmd.com/read/28631737/haematological-cancer-brentuximab-vedotin-a-new-standard-for-cutaneous-t-cell-lymphoma
#6
David Killock
No abstract text is available yet for this article.
June 20, 2017: Nature Reviews. Clinical Oncology
https://www.readbyqxmd.com/read/28622960/treatment-of-peripheral-t-cell-lymphoma-in-community-settings
#7
Tatyana Feldman, Charles M Farber, Kelly Choi, Claudio Faria, Andre Goy, Jacqueline Connors, Dhakshila Paramanathan, Sukhi Kaur, Eric Schultz, Michael McGuire, Stuart L Goldberg
BACKGROUND: Peripheral T-cell lymphomas (PTCLs) represent a rare and heterogeneous group of malignancies that do not have consensus treatment recommendations. Strategies extrapolated from B-cell lymphoma have met with limited efficacy, although T-cell-specific salvage therapies have been recently developed. METHODS: To determine treatment patterns and associated outcomes in PTCL not otherwise specified (PTCL-NOS), anaplastic large T-cell lymphoma (ALCL), and angioimmunoblastic T-cell lymphoma (AITL), a retrospective analysis was undertaken at a large US community oncology network among patients treated between January 2010 and April 2015...
June 2017: Clinical Lymphoma, Myeloma & Leukemia
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
#8
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...
June 6, 2017: Lancet
https://www.readbyqxmd.com/read/28596034/breast-implant-associated-anaplastic-large-cell-lymphoma-the-uk-experience-recommendations-on-its-management-and-implications-for-informed-consent
#9
L Johnson, J M O'Donoghue, N McLean, P Turton, A A Khan, S D Turner, A Lennard, N Collis, M Butterworth, G Gui, J Bristol, J Hurren, S Smith, K Grover, G Spyrou, K Krupa, I A Azmy, I E Young, J J Staiano, H Khalil, F A MacNeill
BACKGROUND: Breast implant-associated anaplastic large-cell lymphoma (BIA-ALCL) is a rare, Non-Hodgkin lymphoma arising in the capsule of breast implants. BIA-ALCL presents as a recurrent effusion and/or mass. Tumours exhibit CD30 expression and are negative for Anaplastic Lymphoma Kinase (ALK). We report the multi-disciplinary management of the UK series and how the stage of disease may be used to stratify treatment. METHODS: Between 2012 and 2016, 23 cases of BIA-ALCL were diagnosed in 15 regional centres throughout the UK...
May 18, 2017: European Journal of Surgical Oncology
https://www.readbyqxmd.com/read/28592744/treatment-advances-and-prognosis-for-patients-with-adult-t-cell-leukemia-lymphoma
#10
Hiroo Katsuya, Kenji Ishitsuka
A classification for adult T-cell leukemia-lymphoma (ATL) based on clinical features was proposed in 1991: acute, lymphoma, chronic, and smoldering types, and their median survival times (MSTs) were reported to be 6.2, 10.2, 24.3 months, and not reached, respectively. Several new therapies for ATL have since been developed, i.e. dose-intensity multi-agent chemotherapies, allogeneic hematopoietic stem cell transplantation (allo-HSCT), monoclonal antibodies, and anti-viral therapy. The monoclonal antibody to CCR4, mogamulizumab, clearly improved response rates in patients with treatment-naïve and relapsed aggressive ATL, and has the potential to provide a survival advantage...
June 8, 2017: Journal of Clinical and Experimental Hematopathology: JCEH
https://www.readbyqxmd.com/read/28586309/italian-real-life-experience-with-brentuximab-vedotin-results-of-a-large-observational-study-on-234-relapsed-refractory-hodgkin-s-lymphoma
#11
Cinzia Pellegrini, Alessandro Broccoli, Alessandro Pulsoni, Luigi Rigacci, Caterina Patti, Guido Gini, Donato Mannina, Monica Tani, Chiara Rusconi, Alessandra Romano, Anna Vanazzi, Barbara Botto, Armando Santoro, Stefan Hoaus, Gian Matteo Rigolin, Pellegrino Musto, Patrizio Mazza, Stefano Molica, Paolo Corradini, Angelo Fama, Francesco Gaudio, Michele Merli, Fioravante Ronconi, Giuseppe Gritti, Daniele Vallisa, Patrizia Tosi, Anna Marina Liberati, Antonello Pinto, Vincenzo Pavone, Filippo Gherlinzoni, Maria Paola Bianchi, Stefano Volpetti, Livio Trentin, Maria Cecilia Goldaniga, Maurizio Bonfichi, Amalia De Renzo, Corrado Schiavotto, Michele Spina, Angelo Michele Carella, Vittorio Stefoni, Lisa Argnani, Pier Luigi Zinzani
A large Italian multicenter observational retrospective study was conducted on the use of brentuximab vedotin (BV) for patients with relapsed Hodgkin's lymphoma (HL) to check if clinical trial results are confirmed even in a real life context. 234 CD30+ HL patients were enrolled. Best response was observed after a median of 4 cycles in 140 patients (59.8%): 74 (31.6%) patients obtained a complete response (CR) and 66 (28.2%) achieved a partial response (PR); overall response rate at the end of the treatment was 48...
May 23, 2017: Oncotarget
https://www.readbyqxmd.com/read/28583265/use-of-the-basophil-activation-test-in-monitoring-clinical-tolerance-after-desensitization-to-brentuximab-vedotin
#12
Raquel de la Varga Martínez, Diego Gutiérrez Fernández, Gustavo A Áñez, Antonio Foncubierta Fernández, José A Andrés García, Fermín Medina Varo
No abstract text is available yet for this article.
June 2017: Annals of Allergy, Asthma & Immunology
https://www.readbyqxmd.com/read/28583027/brentuximab-vedotin-consolidation-post-autologous-stem-cell-transplant-in-hodgkin-lymphoma-patients-at-risk-of-residual-disease-number-needed-to-treat
#13
Ashish Gautam, Yanyan Zhu, Esprit Ma, Shih-Yuan Lee, Erin Zagadailov, Jeremy Teasell, Akshara Richhariya, Vijayveer Bonthapally, Dirk Huebner
The number needed to treat (NNT) with brentuximab vedotin consolidation therapy post-autologous stem cell transplant (ASCT) versus placebo in the phase 3 AETHERA trial to avoid one additional event of disease progression/death was evaluated. AETHERA included 329 Hodgkin lymphoma patients at increased risk of progression post-ASCT who received brentuximab vedotin 1.8 mg/kg (n = 165) or placebo (n = 164) on day 1 of each 21-d cycle (up to 16 cycles). Over 60 months, the NNT with brentuximab vedotin ranged from 4...
June 5, 2017: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/28540671/multidisciplinary-management-of-mycosis-fungoides-s%C3%A3-zary-syndrome
#14
REVIEW
Sara Berg, Jennifer Villasenor-Park, Paul Haun, Ellen J Kim
PURPOSE OF REVIEW: Diagnosis and management of mycosis fungoides and Sézary syndrome (MF/SS) require accurate clinicopathological correlation and a multidisciplinary approach. We reviewed major advances in the field regarding diagnostic and prognostic tools as well as skin-directed therapies (SDTs) and systemic agents for MF/SS published in the past 2 years. RECENT FINDINGS: Improved technology (T-cell receptor high-throughput sequencing) and increased multicenter collaboration (Cutaneous Lymphoma International Consortium) have led to diagnostic/prognostic advances...
June 2017: Current Hematologic Malignancy Reports
https://www.readbyqxmd.com/read/28515253/strategies-for-management-of-relapsed-or-refractory-hodgkin-lymphoma
#15
Leo I Gordon
The advent of effective therapies has improved outcomes for those with newly diagnosed Hodgkin lymphoma (HL), with a resulting cure rate of at least 80%. However, with limited data on therapeutic options in the setting of advanced disease, individualized treatment is recommended, and potential long-term effects of therapy remain a key consideration. At the NCCN 22nd Annual Conference, Dr. Leo I. Gordon explored strategies for systemic therapy in the relapsed or refractory setting, focusing primarily on the standard of high-dose therapy/autologous stem cell rescue, the CD30-targeted antibody drug conjugate brentuximab vedotin, and checkpoint inhibition...
May 2017: Journal of the National Comprehensive Cancer Network: JNCCN
https://www.readbyqxmd.com/read/28513851/population-pharmacokinetics-of-brentuximab-vedotin-in-patients-with-cd30-expressing-hematologic-malignancies
#16
Hong Li, Tae H Han, Naomi N Hunder, Graham Jang, Baiteng Zhao
Brentuximab vedotin, a CD30-directed antibody-drug conjugate (ADC), is approved for treating certain patients with CD30-expressing hematologic malignancies. Its primary mechanism of action is the targeted delivery of a microtubule-disrupting agent, monomethyl auristatin E (MMAE), to CD30-expressing cells. A population pharmacokinetic (PopPK) analysis was conducted to characterize the PK of ADC and unconjugated MMAE in patients with CD30-expressing hematologic malignancies by compartmental analysis and to evaluate the effects of covariates on PK of the ADC...
May 17, 2017: Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/28512788/outcomes-of-patients-with-relapsed-refractory-hodgkin-lymphoma-progressing-after-autologous-stem-cell-transplant-in-the-current-era-of-novel-therapeutics-a-retrospective-analysis
#17
Steven M Bair, Lauren Strelec, Sarah J Nagle, Sunita D Nasta, Daniel J Landsburg, Anthony R Mato, Alison W Loren, Stephen J Schuster, Edward A Stadtmauer, Jakub Svoboda
Patients with relapsed/refractory Hodgkin lymphoma (RR-HL) who progress or relapse following autologous stem cell transplantation (ASCT) have historically had a poor prognosis. Several novel agents, particularly brentuximab vedotin, have shown efficacy in this setting. However, there remains a paucity of data characterizing outcomes outside of clinical trials and how these novel agents have impacted prognosis in general population of patients with RR-HL. Here, we conducted a retrospective analysis to evaluate outcomes in 87 patients with RR-HL with relapse post-ASCT...
May 16, 2017: American Journal of Hematology
https://www.readbyqxmd.com/read/28512672/s%C3%A3-zary-syndrome-with-nodal-cd30-positive-manifestation-treated-with-brentuximab-vedotin-and-extracorporeal-photopheresis
#18
Valeria Behle, Tanja von Braunmühl, Cyrus Sayehli, Anja Gesierich, Matthias Goebeler, Eva Geissinger, Marion Wobser
No abstract text is available yet for this article.
May 17, 2017: Acta Dermato-venereologica
https://www.readbyqxmd.com/read/28488185/where-do-the-new-drugs-fit-in-for-relapsed-refractory-hodgkin-lymphoma
#19
REVIEW
Niloufer Khan, Alison J Moskowitz
The standard approach for relapsed or refractory (rel/ref) Hodgkin lymphoma (HL) following frontline treatment failure is salvage therapy followed by consolidation with high-dose therapy and autologous stem cell transplant (HDT/ASCT). While this overall treatment paradigm has been in place for several decades, recent studies have aimed to improve the efficacy and tolerability of salvage therapies by incorporating newer drugs, such as brentuximab vedotin (BV) and checkpoint inhibitors. Following HDT/ASCT, survival is improved due to the availability of BV and the checkpoint inhibitors, nivolumab and pembrolizumab; however, for patients responding to checkpoint inhibition, the appropriate length of treatment and the role of allogeneic stem cell transplant are unclear...
May 9, 2017: Current Hematologic Malignancy Reports
https://www.readbyqxmd.com/read/28473905/targeting-the-programmed-cell-death-1-pathway-in-hodgkin-lymphoma-the-place-of-nivolumab
#20
REVIEW
Nathan D Gay, Craig Y Okada, Andy I Chen, Emma C Scott
Nivolumab is a humanized immunoglobulin gamma-4 kappa anti-programmed cell death 1 monoclonal antibody that is currently approved in the treatment of several solid tumors and recently gained accelerated approval in classical Hodgkin lymphoma (cHL) that has relapsed or progressed following autologous hematopoietic stem-cell transplantation and post-transplantation brentuximab vedotin. The purpose of this article is to review the immunophysiologic basis, clinical efficacy, and toxicity of nivolumab in the treatment of cHL...
May 2017: Therapeutic Advances in Hematology
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