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https://www.readbyqxmd.com/read/28327905/phase-ii-study-of-idelalisib-a-selective-inhibitor-of-pi3k%C3%AE-for-relapsed-refractory-classical-hodgkin-lymphoma
#1
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
#2
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
#3
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
#4
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...
March 17, 2017: Nature Reviews. Drug Discovery
https://www.readbyqxmd.com/read/28278730/is-cd30-a-predictive-biomarker-for-brentuximab-vedotin
#5
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
#6
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
#7
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
#8
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
#9
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
https://www.readbyqxmd.com/read/28264798/brentuximab-vedotin-in-relapsed-primary-mediastinal-large-b-cell-lymphoma-results-from-a-phase-2-clinical-trial
#10
Pier Luigi Zinzani, Cinzia Pellegrini, Annalisa Chiappella, Alice Di Rocco, Flavia Salvi, Maria Giuseppina Cabras, Lisa Argnani, Vittorio Stefoni
No abstract text is available yet for this article.
March 6, 2017: Blood
https://www.readbyqxmd.com/read/28247950/use-of-brentuximab-vedotin-as-salvage-therapy-pre-allogeneic-stem-cell-transplantation-in-relapsed-refractory-cd30-positive-lympho-proliferative-disorders-a-single-centre-experience
#11
Heshani Mediwake, Kirk Morris, Cameron Curley, Jason Butler, Glen Kennedy
AIM: To assess the outcome of use of brentuximab as a bridge to allogeneic stem cell transplant (SCT) in patient with relapsed / refractory CD30+ classic Hodgkin Lymphoma c(HL) and Anaplastic Large Cell Lymphoma (ALCL). METHODS: Outcomes of consecutive patients with relapsed / refractory cHL / ALCL treated with brentuximab as a bridge to SCT were determined by retrospective review of individual medical records. Survival analysis was measured from start of brentuximab treatment...
March 1, 2017: Internal Medicine Journal
https://www.readbyqxmd.com/read/28219112/brentuximab-vedotin-in-relapsed-refractory-hodgkin-lymphoma-the-hellenic-experience
#12
Maria K Angelopoulou, Theodoros P Vassilakopoulos, Ioannis Batsis, Ioanna Sakellari, Konstantinos Gkirkas, Vasiliki Pappa, Panagiota Giannoulia, Ioannis Apostolidis, Christos Apostolopoulos, Paraskevi Roussou, Panayiotis Panayiotidis, Maria Dimou, Marie-Christine Kyrtsonis, Maria Palassopoulou, Georgios Vassilopoulos, Maria Moschogiannis, Christina Kalpadakis, Dimitrios Margaritis, Alexander Spyridonidis, Eurydiki Michalis, Konstantinos Anargyrou, Panagiotis Repousis, Eleutheria Hatzimichael, Zoi Bousiou, Elias Poulakidas, Dimitrios Grentzelias, Nikolaos Harhalakis, Gerassimos A Pangalis, Achilles Anagnostopoulos, Panagiotis Tsirigotis
This retrospective study aimed to describe the Hellenic experience on the use of brentuximab vedotin (BV) in relapsed/refractory (R/R) Hodgkin lymphoma (HL) given within its indication. From June 2011 to April 2015, ninety-five patients with R/R HL, who received BV in 20 centers from Greece, were analyzed. Their median age was 33 years, and 62% were males. Sixty-seven patients received BV after autologous stem cell transplantation failure, whereas 28 patients were treated with BV without a prior autologous stem cell transplantation, due to advanced age/comorbidities or chemorefractory disease...
February 20, 2017: Hematological Oncology
https://www.readbyqxmd.com/read/28183681/relapse-of-hodgkin-lymphoma-after-autologous-transplantation-time-to-rethink-treatment
#13
REVIEW
Yogesh Jethava, Guru Subramanian Guru Murthy, Mehdi Hamadani
Relapse of Hodgkin lymphoma after autologous hematopoietic cell transplantation (autologous HCT) is a major therapeutic challenge. Its management, at least in younger patients, traditionally involves salvage chemotherapy aiming to achieve disease remission followed by consolidation with allogeneic hematopoietic cell transplantation (allogeneic HCT) in eligible patients. The efficacy of salvage therapy is variable and newer combination chemotherapy regimens have improved the outcomes. Factors such as shorter time to relapse after autologous HCT and poor performance status have been identified as predictors of poor outcome...
February 1, 2017: Hematology/oncology and Stem Cell Therapy
https://www.readbyqxmd.com/read/28152953/cost-effectiveness-of-brentuximab-vedotin-in-relapsed-or-refractory-systemic-anaplastic-large-cell-lymphoma
#14
Denise Zou, Esprit Ma, Peter Sajosi, Andreas Engstrom, Ross Selby, Eugene Benson, Jeremy Teasell, Akshara Richhariya, Andrew Briggs, Vijayveer Bonthapally
18 Background: Systemic anaplastic large cell lymphoma (sALCL) is a rare T-cell lymphoma. For patients who fail front-line therapy, outcomes are poor and there is no current defined standard of care. Brentuximab vedotin has demonstrated high objective response rates and is approved for patients with relapsed or refractory (R/R) sALCL. However, the cost-effectiveness of brentuximab vedotin compared with conventional chemotherapy has not been explored. METHODS: A lifetime Excel-based partitioned survival model was used to compare survival outcomes from the pivotal phase-2 single-arm brentuximab vedotin trial of 58 R/R sALCL patients with good Eastern Corporative Oncology Group (ECOG) performance status after one or more prior therapies (SG035-0004); with 40 sALCL patients from a Canadian cancer registry receiving first-line conventional salvage chemotherapy (65% with ECOG 0 or 1) between 1980 and 2012 and followed for up to 20 years...
March 2016: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28152950/brentuximab-vedotin-in-relapsed-refractory-hodgkin-lymphoma-following-autologous-stem-cell-transplant-a-cost-effectiveness-analysis-updated-with-5-year-follow-up-data-from-the-pivotal-trial
#15
Gemma Kay, Esprit Ma, Beth Woods, James Eaton, Peter Sajosi, Andreas Engstrom, Ross Selby, Eugene Benson, Jeremy Teasell, Akshara Richhariya, Andrew Briggs, Vijayveer Bonthapally
19 Background: In 2015, the Scottish Medicines Consortium (SMC) made a positive recommandation for brentuximab vedotin (BV) in patients with relapsed or refractory (R/R) Hodgkin lymphoma (HL) who have received autologous stem cell transplantation (ASCT) based on 3-year follow-up data from the pivotal phase 2 single-arm trial (SG035-0003; NCT00848926). At 3-years, the incremental cost-effectiveness ratio (ICER) for brentuximab vedotin compared with chemotherapy +/- radiotherapy (C/R) was £43,731 per quality-adjusted life year (QALY)...
March 2016: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28152678/brentuximab-vedotin-bv-consolidation-post-autologous-stem-cell-transplant-asct-in-patients-pts-with-hodgkin-lymphoma-hl-at-risk-of-residual-disease-number-needed-to-treat-nnt-analysis
#16
Dirk Huebner, Yanyan Zhu, Esprit Ma, Shih-Yuan Lee, Erin Zagadailov, Jeremy Teasell, Akshara Richhariya, Vijayveer Bonthapally
20 Background: AETHERA (NCT01100502) is a randomized Phase 3 study of BV and best supportive care (BSC) vs placebo (PBO) and BSC in the treatment of pts at risk of residual HL post-ASCT. BV consolidation therapy post-ASCT significantly improved progression-free survival (PFS) by independent review vs PBO (HR = 0.57, P = 0.001) and was FDA approved. Most common grade ≥ 3 adverse events were neutropenia (29% BV vs 10% PBO) and peripheral sensory neuropathy (10% vs 1%). The aim of this study was to determine the NNT with BV to avoid 1 additional event, disease progression/death...
March 2016: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28138786/low-dose-pembrolizumab-for-relapsed-refractory-hodgkin-lymphoma-high-efficacy-with-minimal-toxicity
#17
MULTICENTER STUDY
Thomas S Y Chan, Tsan-Hei Luk, June S M Lau, Pek-Lan Khong, Yok-Lam Kwong
Five patients with refractory/relapsed classical Hodgkin lymphoma (cHL), four having failed multiple lines of chemotherapy and brentuximab vedotin, were treated with low-dose pembrolizumab (median dose 100 mg, range: 100-200 mg, every 3 weeks). Complete response (CR) was achieved in four patients (80%), after a median cumulative dose of merely 495 (300-800) milligrams. Three CR patients have continued to receive pembrolizumab for a median of 16 (14-25) cycles, remaining in CR for a median of 18 (9-18) months...
April 2017: Annals of Hematology
https://www.readbyqxmd.com/read/28134921/improving-outcomes-after-allogeneic-hematopoietic-cell-transplantation-for-hodgkin-lymphoma-in-the-brentuximab-vedotin-era
#18
L Hegerova, Q Cao, A Lazaryan, B L McClune, D J Weisdorf, C G Brunstein, V Bachanova
Allogeneic hematopoietic cell transplantation (alloHCT) remains a valuable treatment alternative for relapsed/refractory (R/R) Hodgkin lymphoma (HL). Data on alloHCT outcomes in the era of new HL therapies are needed. We evaluated 72R/R HL patients who received reduced intensity conditioning alloHCT and compared the time periods 2009-2013 (n=20) with 2000-2008 (n=52). Grafts included HLA-matched sibling (35%), unrelated donor (8%) and umbilical cord blood (56%). In the recent period, patients more often received brentuximab vedotin (BV, 60% vs 2%), had fewer comorbidities (Sorror index 0: 60% vs 12%) and were in complete remission (50% vs 23%)...
January 30, 2017: Bone Marrow Transplantation
https://www.readbyqxmd.com/read/28119332/brentuximab-beats-standard-therapies-for-ctcl
#19
(no author information available yet)
Compared with a physician's choice of either methotrexate or bexarotene, the CD30-directed antibody-drug conjugate brentuximab vedotin led to significantly superior clinical responses in patients with cutaneous T-cell lymphomas, according to the results of the international phase III ALCANZA trial.
January 24, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28115372/peripheral-t-cell-lymphoma-not-otherwise-specified
#20
REVIEW
Alessandro Broccoli, Pier Luigi Zinzani
Peripheral T-cell lymphoma, not otherwise specified, is a broad category of biologically and clinically heterogeneous diseases that cannot be further classified into any other of the existing entities defined by the World Health Organization classification. Anthracycline-containing regimens, namely cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP), nowadays represent the standard first-line treatment; for patients who achieve a satisfactory response, a consolidation by means of autologous stem cell transplantation may offer a greater chance of long-term survival...
March 2, 2017: Blood
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