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https://www.readbyqxmd.com/read/29415977/composite-lymphoma-as-co-occurrence-of-advanced-chronic-lymphocytic-leukemia-small-lymphocytic-lymphoma-carrying-trisomy-12-and-t-14-18-and-peripheral-t-cell-lymphoma
#1
Yumi Aoyama, Taiichi Kodaka, Yuriko Zushi, Yuta Goto, Hiroko Tsunemine, Tomoo Itoh, Takayuki Takahashi
Composite lymphoma is defined as the co-occurrence of two types of lymphoma, comprising 1-4% of lymphomas, and the association of B-cell-type chronic lymphocytic leukemia (B-CLL)/small lymphocytic lymphoma and peripheral T-cell lymphoma (PTCL) is rare. Here, we report a case (77-year-old woman) of advanced B-CLL complicated by newly appearing PTCL. Two years after the onset of B-CLL, CLL cells acquired CD38 antigen expression and the disease entity became CLL/prolymphocytic leukemia. Trisomy 12 and t(14;18) karyotypes were observed...
February 8, 2018: Journal of Clinical and Experimental Hematopathology: JCEH
https://www.readbyqxmd.com/read/29414262/antibody-drug-conjugates-for-cancer-treatment
#2
John M Lambert, Anna Berkenblit
The concept of exploiting the specific binding properties of monoclonal antibodies as a mechanism for selective delivery of cytotoxic agents to tumor cells is an attractive solution to the challenge of increasing the therapeutic index of cell-killing agents for treating cancer. All three parts of an antibody-drug conjugate (ADC)-the antibody, the cytotoxic payload, and the linker chemistry that joins them together-as well as the biologic properties of the cell-surface target antigen are important in designing an effective anticancer agent...
January 29, 2018: Annual Review of Medicine
https://www.readbyqxmd.com/read/29409861/mathematical-modeling-of-antibody-drug-conjugates-with-the-target-and-tubulin-dynamics-to-predict-auc
#3
Jong Hyuk Byun, Il Hyo Jung
Antibody drug conjugates (ADCs)are one of the most recently developed chemotherapeutics to treat some types of tumor cells. They consist of monoclonal antibodies (mAbs), linkers, and potent cytotoxic drugs. Unlike common chemotherapies, ADCs combine selectively with a target at the surface of the tumor cell, and a potent cytotoxic drug (payload) effectively prevents microtubule polymerization. In this work, we construct an ADC model that considers both the target of antibodies and the receptor (tubulin) of the cytotoxic payloads...
January 31, 2018: Journal of Theoretical Biology
https://www.readbyqxmd.com/read/29397528/the-future-of-combination-therapies-for-peripheral-t-cell-lymphoma-ptcl
#4
REVIEW
Helen Ma, Ardy Davarifar, Jennifer E Amengual
PURPOSE OF REVIEW: Peripheral T cell lymphoma is a rare heterogeneous group of diseases which are characterized by poor outcomes to treatment and short overall survival. In the past decade, several new therapies targeting T cell biology have been approved in the relapsed setting. These new therapies, such as pralatrexate, romidepsin, belinostat, and brentuximab vedotin, have begun to make their way into practice. Despite these advances, outcomes have not changed dramatically. In recent years, efforts have been made to incorporate these new therapies into combination strategies to treat this challenging disease entity...
February 3, 2018: Current Hematologic Malignancy Reports
https://www.readbyqxmd.com/read/29391331/improvement-of-cutaneous-anaplastic-large-cell-lymphoma-by-brentuximab-vedotin-monotherapy
#5
Takashi Onaka, Tomoya Kitagawa, Chika Kawakami, Akihito Yonezawa
No abstract text is available yet for this article.
February 2, 2018: Turkish Journal of Haematology: Official Journal of Turkish Society of Haematology
https://www.readbyqxmd.com/read/29390984/phase-i-clinical-study-of-brentuximab-vedotin-sgn-35-involving-children-with-recurrent-or-refractory-cd30-positive-hodgkin-s-lymphoma-or-systemic-anaplastic-large-cell-lymphoma-rationale-design-and-methods-of-bv-hlalcl-study-study-protocol
#6
Masahiro Sekimizu, Akihiro Iguchi, Tetsuya Mori, Yuhki Koga, Akiko Kada, Akiko M Saito, Keizo Horibe
BACKGROUND: Hodgkin's lymphoma (HL) and anaplastic large-cell lymphoma (ALCL) are the two most common tumors expressing CD30. Internationally, a clinical study that is being conducted involving adults with recurrent or refractory HL or ALCL suggests efficacy of brentuximab vedotin (SGN-35). Pediatric patients should be given medicines that have been appropriately evaluated for their use. In the past, however, new approved drugs have been used for pediatric patients without the confirmation of safety and efficacy in pediatric patients...
February 1, 2018: BMC Cancer
https://www.readbyqxmd.com/read/29381234/balancing-early-access-with-uncertainties-in-evidence-for-drugs-authorized-by-prospective-case-series-systematic-review-of-reimbursement-decisions
#7
Susanna M Wallerstedt, Martin Henriksson
AIMS: To review clinical and cost-effectiveness evidence underlying reimbursement decisions relating to drugs whose authorization mainly is based on evidence from prospective case series. METHODS: A systematic review of all new drugs evaluated in 2011-2016 within a health care profession-driven resource prioritization process, with a market approval based on prospective case series, and a reimbursement decision by the Swedish Dental and Pharmaceutical Benefits Board (TLV)...
January 30, 2018: British Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/29377077/population-pk-and-exposure-response-relationships-for-the-antibody-drug-conjugate-brentuximab-vedotin-in-ctcl-patients-in-the-phase-iii-alcanza-study
#8
A Suri, D R Mould, Y Liu, G Jang, K Venkatakrishnan
The antibody-drug conjugate (ADC) brentuximab vedotin consists of the CD30-directed antibody attached to the microtubule-disrupting agent monomethyl auristatin E (MMAE). In pharmacokinetic models, including data from six studies (380 patients with classical Hodgkin, systemic anaplastic large cell, and cutaneous T-cell [CTCL] lymphomas), lower clearance of ADC and modestly higher ADC exposure in CTCL patients did not translate into higher MMAE exposure. In CTCL patients from the phase III ALCANZA study (n = 66), improved progression-free survival with brentuximab vedotin vs...
January 29, 2018: Clinical Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/29369629/immolation-of-p-aminobenzyl-ether-linker-and-payload-potency-and-stability-determine-the-cell-killing-activity-of-antibody-drug-conjugates-with-phenol-containing-payloads
#9
Donglu Zhang, Hoa Le, Josefa Dela Cruz-Chuh, Sudheer Bobba, Jun Guo, Leanna Staben, Chenghong Zhang, Yong Ma, Katherine Ruth Kozak, Gail D Lewis-Phillips, Breanna Vollmar, Jack Sadowsky, Richard Vandlen, Binqing Wei, Dian Su, Peter Wei-Jen Fan, Peter S Dragovich, Cyrus Khojasteh, Cornelis E C A Hop, Thomas H Pillow
The valine-citrulline (Val-Cit) dipeptide and p-aminobenzyl (PAB) spacer have been commonly used as a cleavable self-immolating linker in ADC design including in the clinically approved ADC, brentuximab vedotin (Adcetris®). When the same linker was used to connect to the phenol of the cyclopropabenzindolone (CBI) (P1), the resulting ADC1 showed loss of potency in CD22 target-expressing cancer cell lines (e.g. BJAB, WSU-DLCL2). In comparison, the conjugate (ADC2) of a cyclopropapyrroloindolone (CPI) (P2) was potent despite the two corresponding free drugs having similar picomolar cell killing activity...
January 25, 2018: Bioconjugate Chemistry
https://www.readbyqxmd.com/read/29366607/soho-state-of-the-art-updates-and-next-questions-hodgkin-lymphoma
#10
REVIEW
Marcus P Watkins, Michelle A Fanale, Nancy L Bartlett
Until recently, advances in classic Hodgkin lymphoma (HL) treatment primarily consisted of minor modifications of highly effective decades-old chemotherapy and radiation approaches. In early-stage disease, excellent outcomes have been reported with fewer cycles of chemotherapy, lower doses, smaller radiation fields and in some circumstances, radiation elimination. In advanced-stage disease, maintaining the dose intensity of standard chemotherapy regimens has resulted in modest improvements in outcomes. During the past decade, the use of early interim positron emission tomography (PET) scans to escalate or de-escalate treatment has been the subject of intense investigation with the goal of maximizing efficacy and minimizing toxicity...
January 4, 2018: Clinical Lymphoma, Myeloma & Leukemia
https://www.readbyqxmd.com/read/29357803/adme-considerations-for-the-development-of-biopharmaceutical-conjugates-using-cleavable-linkers
#11
L Nathan Tumey, Sean Amgen Com Han
The recent approval of trastuzumab emtansine (Kadcyla®) and brentuximab vedotin (Adcetris®) has spurred tremendous investment in new approaches for the targeted delivery of pharmaceutical agents. Targeted delivery approaches, such as antibody drug conjugates (ADCs), typically rely on an endogenous or exogenous "trigger" that results in the release of the pharmacologically active agent at the intended site of action. Lysosomal and intracellular triggers include proteolytic cleavage, glycolytic cleavage, phosphatase cleavage, hydrolytic cleavage, and reductive cleavage...
January 18, 2018: Current Topics in Medicinal Chemistry
https://www.readbyqxmd.com/read/29343970/a-retrospective-examination-of-the-us-food-and-drug-administration-s-clinical-pharmacology-reviews-of-oncology-biologics-for-potential-use-of-therapeutic-drug-monitoring
#12
Brett Fleisher, Sihem Ait-Oudhia
Background: Biologics have gained traction for use in oncology, but have demonstrate clinical variability for efficacy and safety. Therapeutic drug monitoring (TDM) can benefit patients' outcomes from a biologic therapy when the latter has a defined therapeutic window. A clinically relevant therapeutic window may exist for biologics with established exposure-response (E-R) relationships for efficacy and/or safety and a documented maximum tolerated dose (MTD). Additionally, the inter-individual variability (IIV) on the clearance (CL) parameter could determine risks for patients falling outside the proposed therapeutic window...
2018: OncoTargets and Therapy
https://www.readbyqxmd.com/read/29334819/management-of-hodgkin-lymphoma-in-the-era-of-brentuximab-vedotin-real-world-data-from-five-european-countries
#13
Graham P Collins, Antonio Rueda, Gilles Salles, Bastian von Tresckow, Francesco Zaja
We examined real-world data on management of relapsed/refractory Hodgkin lymphoma (R/R HL) in five European countries and the consistency of these data with guideline recommendations. Retrospective clinical and epidemiologic data for 509 patients with R/R HL treated between January 2014 and March 2015 were collected at centers in France, Germany, Italy, Spain, and the United Kingdom. Mean age was 46.3 years; 73.3% were receiving second-line therapy for a first relapse during the reporting period. Most patients received ABVD as front-line chemotherapy, except in Germany where escalated BEACOPP was used more often...
January 16, 2018: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/29333400/brentuximab-vedotin-clinical-updates-and-practical-guidance
#14
REVIEW
Jun Ho Yi, Seok Jin Kim, Won Seog Kim
Brentuximab vedotin (BV), a potent antibody-drug conjugate, targets the CD30 antigen. Owing to the remarkable efficacy shown in CD30-positive lymphomas, such as Hodgkin's lymphoma and systemic anaplastic large-cell lymphoma, BV was granted accelerated approval in 2011 by the US Food and Drug Administration. Thereafter, many large-scale trials in various situations have been performed, which led to extensions of the original indication. The aim of this review was to describe the latest updates on clinical trials of BV and the in-practice guidance for the use of BV...
December 2017: Blood Research
https://www.readbyqxmd.com/read/29313932/brentuximab-vedotin-is-an-effective-therapy-for-cd30-mycosis-fungoides-and-cutaneous-anaplastic-large-cell-lymphoma-what-is-the-cost
#15
J J Scarisbrick
No abstract text is available yet for this article.
December 2017: British Journal of Dermatology
https://www.readbyqxmd.com/read/29283169/haematological-cancer-brentuximab-effective-in-untreated-hodgkin-lymphoma
#16
Peter Sidaway
No abstract text is available yet for this article.
December 28, 2017: Nature Reviews. Clinical Oncology
https://www.readbyqxmd.com/read/29280762/brentuximab-vedotin-with-avd-shows-safety-in-the-absence-of-strong-cyp3a4-inhibitors-in-newly-diagnosed-hiv-associated-hodgkin-lymphoma
#17
Paul G Rubinstein, Page C Moore, Michelle A Rudek, David H Henry, Juan C Ramos, Lee Ratner, Erin Reid, Elad Sharon, Ariela Noy
OBJECTIVE: Brentuximab vedotin (BV) is an FDA approved anti-CD30 antibody drug conjugate potently active in Hodgkin lymphoma (HL). Trials of BV with doxorubicin, vinblastine, and dacarbazine (AVD-BV) excluded patients with HIV. We studied the safety of (AVD-BV) in newly diagnosed HIV-associated classical Hodgkin lymphoma (HIV-cHL). DESIGN AND METHODS: Patients diagnosed with Stage II-IV HIV-cHL received AVD-BV on days 1 and 15 every 28 days for 6 cycles. Anti-HIV medications with strong CYP3A4 inhibition were excluded...
December 26, 2017: AIDS
https://www.readbyqxmd.com/read/29279550/anaplastic-large-cell-lymphoma-pathology-genetics-and-clinical-aspects
#18
Naoko Tsuyama, Kana Sakamoto, Seiji Sakata, Akito Dobashi, Kengo Takeuchi
Anaplastic large cell lymphoma (ALCL) was first described in 1985 as a large-cell neoplasm with anaplastic morphology immunostained by the Ki-1 antibody, which recognizes CD30. In 1994, the nucleophosmin (NPM)-anaplastic lymphoma kinase (ALK) fusion receptor tyrosine kinase was identified in a subset of patients, leading to subdivision of this disease into ALK-positive and -negative ALCL in the present World Health Organization classification. Due to variations in morphology and immunophenotype, which may sometimes be atypical for lymphoma, many differential diagnoses should be considered, including solid cancers, lymphomas, and reactive processes...
2017: Journal of Clinical and Experimental Hematopathology: JCEH
https://www.readbyqxmd.com/read/29276023/salvage-regimens-for-hodgkin-s-lymphoma-in-the-brentuximab-vedotin-era
#19
Umberto Vitolo, Annalisa Chiappella
No abstract text is available yet for this article.
December 21, 2017: Lancet Oncology
https://www.readbyqxmd.com/read/29276022/brentuximab-vedotin-plus-bendamustine-in-relapsed-or-refractory-hodgkin-s-lymphoma-an-international-multicentre-single-arm-phase-1-2-trial
#20
Owen A O'Connor, Jennifer K Lue, Ahmed Sawas, Jennifer E Amengual, Changchun Deng, Matko Kalac, Lorenzo Falchi, Enrica Marchi, Ithamar Turenne, Renee Lichtenstein, Celeste Rojas, Mark Francescone, Lawrence Schwartz, Bin Cheng, Kerry J Savage, Diego Villa, Michael Crump, Anca Prica, Vishal Kukreti, Serge Cremers, Joseph M Connors, John Kurvuilla
BACKGROUND: Brentuximab vedotin is currently approved for patients with relapsed or refractory Hodgkin's lymphoma who previously received an autologous stem cell transplant or two previous multiagent chemotherapy regimens, and for patients with relapsed or refractory systemic anaplastic large-T-cell lymphoma who previously received at least one chemotherapy regimen. A high proportion of patients with CD30-expressing relapsed or refractory lymphomas have durable responses to single-agent brentuximab vedotin and show longer progression-free survival than do patients treated with chemotherapy...
December 21, 2017: Lancet Oncology
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