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https://www.readbyqxmd.com/read/27913499/novel-agents-and-strategies-in-transplant-eligible-patients-with-relapsed-and-refractory-hodgkin-lymphoma
#1
Craig Moskowitz
The majority of patients with Hodgkin lymphoma are cured with frontline therapy; however, 10% to 15% with early-stage disease and 20% to 30% with advanced stage require second-line therapy that includes a potentially curative transplant, of which an additional 50% to 55% are cured. Those with multiply relapsed disease traditionally would receive novel agents on a clinical trial or combination chemotherapy as a potential bridge to an allogeneic stem cell transplant. This treatment paradigm has changed with the availability of brentuximab vedotin, an antibody drug conjugate used pre- and post-ASCT, as well as for palliation...
December 2, 2016: Hematology—the Education Program of the American Society of Hematology
https://www.readbyqxmd.com/read/27881581/nivolumab-in-the-treatment-of-hodgkin-lymphoma
#2
Stephen M Ansell
Despite an extensive immune infiltrate that is recruited to the tumor by malignant Reed Sternberg cells in Hodgkin lymphoma, the antitumor immune response is ineffective and unable to eradicate the malignant cells. The ineffective immune response is in part due to PD-1 signaling that renders intratumoral immune cells anergic. Reed Sternberg cells have been shown to upregulate expression of the PD-1 ligands, PD-L1 and PD-L2, due to either genetic alterations at chromosome 9p24.1 or Epstein Barr virus infection, and these ligands suppress the function of PD-1+ intratumoral T-cells...
November 23, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/27868471/brentuximab-vedotin-activity-in-diffuse-large-b-cell-lymphoma-with-cd30-undetectable-by-visual-assessment-of-conventional-immunohistochemistry
#3
Nancy L Bartlett, Mitchell R Smith, Tanya Siddiqi, Ranjana H Advani, Owen A O'Connor, Jeff P Sharman, Tatyana Feldman, Kerry J Savage, Andrei R Shustov, Catherine S Diefenbach, Yasuhiro Oki, Maria Corinna Palanca-Wessels, Mayur Uttarwar, Martha Li, Jing Yang, Eric D Jacobsen
This phase 2 study evaluated brentuximab vedotin monotherapy in CD30-expressing DLBCL; after several patients with little to no CD30 achieved a complete remission (CR), the study evaluated treatment of DLBCL with undetectable CD30 (CD30u) by local visual immunohistochemistry (vIHC). Sixteen of 52 CD30u DLBCL patients (31%) had an objective response (6 CRs [12%]). Median progression-free survival (PFS) was 1.4 months (range, 0.4-15.6) and median overall survival (OS) was 7.5 months (range, 0.7-18.6+). Subsequent CD30 expression quantitated by computer-assisted digital image analysis (cIHC) showed that 11 of 16 CD30u DLBCL responders had ≥1% CD30...
November 20, 2016: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/27837256/pharmacokinetics-immunogenicity-and-safety-of-weekly-dosing-of-brentuximab-vedotin-in-pediatric-patients-with-hodgkin-lymphoma
#4
Jamie E Flerlage, Monika L Metzger, Jianrong Wu, John C Panetta
PURPOSE: Because of the observed success of phase I/II trials, the novel anti-CD30 agent brentuximab vedotin is now being evaluated as a frontline agent in the high-risk pediatric Hodgkin lymphoma trial HLHR13. The objectives of this study were to evaluate the pharmacokinetic variability during weekly dosing of 1.2 mg/kg of brentuximab vedotin, determine factors that may explain this variability, compare our drug exposure with published data, and evaluate toxicity of brentuximab vedotin in the pediatric population...
November 11, 2016: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/27824517/a-rare-case-of-orbital-hodgkin-lymphoma-demonstrating-therapeutic-response-to-a-novel-systemic-medication
#5
Brynn N Wajda, Michael P Rabinowitz
Orbital Hodgkin lymphoma is infrequent, representing less than 1% of adult orbital malignancies. It is typically seen in the setting of terminally advanced systemic disease. This case highlights orbital, head, and neck disease in a systemically stable individual treated with the novel anti-CD30 monoclonal antibody brentuximab vedotin.
November 8, 2016: Orbit
https://www.readbyqxmd.com/read/27807492/novel-brentuximab-vedotin-combination-therapies-show-promising-activity-in-highly-refractory-cd30-non-hodgkin-lymphoma-a-case-series-and-review-of-the-literature
#6
Wilfred Delacruz, Robert Setlik, Arash Hassantoufighi, Shyam Daya, Susannah Cooper, Dale Selby, Alexander Brown
Non-Hodgkin lymphomas (NHLs) are a heterogeneous group of hematologic malignancies which typically respond to standard first-line chemoimmunotherapy regimens. Unfortunately, patients with refractory NHL face a poor prognosis and represent an unmet need for improved therapeutics. We present two cases of refractory CD30+ NHL who responded to novel brentuximab vedotin- (BV-) based regimens. The first is a patient with stage IV anaplastic large cell lymphoma (ALCL) with cranial nerve involvement who failed front-line treatment with cyclophosphamide, doxorubicin, vincristine, etoposide, and prednisone (CHOEP) and second line cyclophosphamide, vincristine, doxorubicin, dexamethasone alternating with high-dose methotrexate (MTX), and cytarabine (hyperCVAD) with intrathecal- (IT-) MTX and IT-cytarabine, but responded when BV was substituted for vincristine (hyperCBAD)...
2016: Case Reports in Oncological Medicine
https://www.readbyqxmd.com/read/27757215/brentuximab-vedotin-therapy-for-cutaneous-lesions-in-t-prolymphocytic-leukemia-a-case-report
#7
Jordan Senchak, Peter Pickens
We present an 88-year-old male with simultaneous T-cell prolymphocytic leukemia and stable smoldering myeloma with excellent initial response to three months of alemtuzumab. The patient relapsed at twelve months with severe cutaneous disease. Biopsy of a representative plaque demonstrated CD30 positivity in rare malignant lymphocytes. The patient demonstrated no response to reintroduction with a full course of alemtuzumab. He was therefore treated with brentuximab vedotin, resulting in partial remission of skin involvement that persisted for three months...
September 28, 2016: Hematology Reports
https://www.readbyqxmd.com/read/27753058/checkpoint-inhibition-in-hodgkin-lymphoma-saving-the-best-for-last
#8
Richard J Lin, Catherine S Diefenbach
Hodgkin lymphoma is a unique disease entity characterized by a low number of neoplastic tumor cells surrounded by an inflammatory microenvironment composed of dysfunctional immune cells. Recent molecular and genetic studies have revealed that upregulation of the immune checkpoint pathway programmed death 1/programmed death ligand 1 is a key oncogenic driver of Hodgkin lymphoma. Corroborating these mechanistic studies, early-phase clinical trials using the checkpoint inhibitors nivolumab and pembrolizumab in treatment regimens for relapsed and/or refractory Hodgkin lymphoma have demonstrated impressive response rates, a promising durability of response, and a favorable side-effect profile...
October 15, 2016: Oncology (Williston Park, NY)
https://www.readbyqxmd.com/read/27739312/-treatment-of-relapsed-and-refractory-hodgkin-lymphoma-recommendations-of-the-czech-hodgkin-lymphoma-study-group
#9
H Móciková, J Marková, Ľ Gahérová, Z Král, A Sýkorová, D Belada, V Procházka, L Martinková, T Papajík, T Kozák
High-dose chemotherapy with autologous stem cell transplantation remains the current standard of treatment for young patients with Hodgkin lymphoma in first relapse or in those who are refractory to first-line treatment. The most important prognostic factors in relapses are clinical stage IV, poor performance status, bulky mass, and less than partial remission after salvage chemotherapy. Standard salvage chemotherapy in relapse before autologous transplantation has not been defined; however, DHAP and ICE are most frequently used in this setting...
2016: Klinická Onkologie: Casopis Ceské a Slovenské Onkologické Spolecnosti
https://www.readbyqxmd.com/read/27715057/structure-determinants-of-lagunamide-a-for-anticancer-activity-and-its-molecular-mechanism-of-mitochondrial-apoptosis
#10
Xiaoxing Huang, Wei Huang, Li Li, Xihuan Sun, Siyang Song, Qingyan Xu, Lianru Zhang, Bang-Guo Wei, Xianming Deng
Marine natural products are served as attractive source of anticancer therapeutics, with the great success of "first-in-class" drugs, such as Yondelis, Halaven, and Brentuximab vendotin. Lagunamides A-C from marine cyanobacterium, Lyngbya majuscula, exhibit exquisite growth inhibitory activities against cancer cells. In this study, we have systematically investigated the structure-activity relationships (SAR) of a concise collection of lagunamide A and its analogs constructed by total chemical synthesis against a broad panel of cancer cells derived from various tissues or organs, including A549, HeLa, U2OS, HepG2, BEL-7404, BGC-823, HCT116, MCR-7, HL-60, and A375...
October 7, 2016: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/27711130/highly-diverse-efficacy-of-salvage-treatment-regimens-for-relapsed-or-refractory-peripheral-t-cell-lymphoma-a-systematic-review
#11
Ya-Ting Yang, Cheng-Jeng Tai, Chiehfeng Chen, Hong-Cheng Wu, Natalia Mikhaylichenko, Hsien-Tsai Chiu, Yun-Yi Chen, Yi-Hsin Elsa Hsu
BACKGROUND: The goal of this study was to perform a systematic review to examine the efficacy and safety of various salvage therapy regimens on patients with relapsed/refractory PTCL. METHOD: The electronic searches were performed using PubMed, Cochrane Library, EMBASE, and Web of Science from inception through June 2015, with search terms related to relapsed/refractory PTCL, salvage chemotherapy regimens, and clinical trials. An eligible study met the following inclusion criteria: (1) Patients had refractory or relapsed PTCL; (2) drug regimens were used for salvage therapy; (3) the study was a clinical trial; (4) the study reported on a series of at least 10 patients of PTCL...
2016: PloS One
https://www.readbyqxmd.com/read/27703376/a-case-report-and-literature-review-of-primary-resistant-hodgkin-lymphoma-a-response-to-anti-pd-1-after-failure-of-autologous-stem-cell-transplantation-and-brentuximab-vedotin
#12
Peipei Xu, Fan Wang, Chaoyang Guan, Jian Ouyang, Xiaoyan Shao, Bing Chen
Hodgkin lymphoma (HL) is a highly curable hematologic malignancy, and ~70% of cases can be cured with combination chemotherapy with or without radiation. However, patients with primary resistant disease have a cure rate of <30%. For such patients, high-dose chemotherapy followed by autologous stem cell transplantation (ASCT) is considered to be the standard treatment. If patients fail to respond to ASCT or relapse soon thereafter, they usually receive another ASCT, allogeneic stem cell transplantation or treatment with novel agents...
2016: OncoTargets and Therapy
https://www.readbyqxmd.com/read/27675802/brentuximab-vedotin-and-avd-chemotherapy-followed-by-isrt-a-safe-primary-treatment-regimen-for-early-stage-unfavorable-hodgkin-lymphoma
#13
J C Yang, A Kumar, K L Chapman, L S Constine, C H Moskowitz, J Yahalom
No abstract text is available yet for this article.
October 1, 2016: International Journal of Radiation Oncology, Biology, Physics
https://www.readbyqxmd.com/read/27649689/quality-of-life-results-from-a-phase-3-study-of-brentuximab-vedotin-consolidation-following-autologous-haematopoietic-stem-cell-transplant-for-persons-with-hodgkin-lymphoma
#14
Scott D Ramsey, Auayporn Nademanee, Tamas Masszi, Jerzy Holowiecki, Muneer Abidi, Andy Chen, Patrick Stiff, Simonetta Viviani, John W Sweetenham, John Radford, Yanyan Zhu, Vijayveer Bonthapally, Elizabeth Thomas, Akshara Richhariya, Naomi N Hunder, Jan Walewski, Craig H Moskowitz
Brentuximab vedotin (BV) significantly improved progression-free survival in a phase 3 study in patients with relapsed or refractory Hodgkin lymphoma (RR-HL) post-autologous-haematopoietic stem cell transplant (auto-HSCT); we report the impact of BV on quality of life (QOL) from this trial. The European Quality of Life five dimensions questionnaire was administered at the beginning of each cycle, end of treatment, and every 3 months during follow-up; index value scores were calculated using the time trade-off (TTO) method for UK-weighted value sets...
September 21, 2016: British Journal of Haematology
https://www.readbyqxmd.com/read/27647407/-a-case-report-of-refractory-alk-positive-anaplastic-large-cell-lymphoma-treated-with-brentuximab-vedotin
#15
Z G Cao, Z H Wang, J Z Sun, M Liu, X Y Zhou, Q M Yang
No abstract text is available yet for this article.
September 23, 2016: Zhonghua Zhong Liu za Zhi [Chinese Journal of Oncology]
https://www.readbyqxmd.com/read/27613003/cd30-and-cd30-targeted-therapies-in-hodgkin-lymphoma-and-other-b-cell-lymphomas
#16
Geetika Bhatt, Kami Maddocks, Beth Christian
Evolution of cancer therapeutics has resulted in the development of agents with varying mechanisms of selective target inhibition. One such therapeutic approach is utilizing antibody-drug conjugates (ADCs), the combination of a cytotoxic agent linked with a monoclonal antibody, to achieve localization of the target and internalization of the cytotoxic agent in order to maximize efficacy with fewer toxicities. This review focuses on CD30 as a therapeutic target and the development and clinical activity of the ADC brentuximab vedotin in Hodgkin lymphoma (HL) and other B cell lymphomas...
September 9, 2016: Current Hematologic Malignancy Reports
https://www.readbyqxmd.com/read/27592544/therapeutic-use-of-brentuximab-vedotin-in-cd30-hematologic-malignancies
#17
Alberto Fabbri, Emanuele Cencini, Alessandro Gozzetti, Luana Schiattone, Monica Bocchia
The CD30 antigen is strongly expressed on neoplastic cells in classical Hodgkin lymphoma (HL), anaplastic large cell lymphoma (ALCL) and other hematologic malignancies (such as DLBCL and cutaneous TCL), while is almost undetectable on healthy tissues, representing an ideal immunotherapeutic target. Since unconjugated anti-CD30 antibody (SGN-30) demonstrated limited clinical activity, researchers' effort aimed to create an antibody-drug conjugate (ADC), leading to discovery of SGN-35 (brentuximab vedotin), in which an anti-CD30 antibody is linked to the antimitotic agent monomethyl auristatin E (MMAE)...
September 2, 2016: Anti-cancer Agents in Medicinal Chemistry
https://www.readbyqxmd.com/read/27589029/impact-of-organic-modifier-and-temperature-on-protein-denaturation-in-hydrophobic-interaction-chromatography
#18
Balázs Bobaly, Alain Beck, Jean-Luc Veuthey, Davy Guillarme, Szabolcs Fekete
The goal of this study was to better understand the chromatographic conditions in which monoclonal antibodies (mAbs) of broad hydrophobicity scale and a cysteine conjugated antibody-drug conjugate (ADCs), namely brentuximab-vedotin, could denaturate. For this purpose, some experiments were carried out in HIC conditions using various organic modifier in natures and proportions, different mobile phase temperatures and also different pHs. Indeed, improper analytical conditions in hydrophobic interaction chromatography (HIC) may create reversed-phase (RP) like harsh conditions and therefore protein denaturation...
November 30, 2016: Journal of Pharmaceutical and Biomedical Analysis
https://www.readbyqxmd.com/read/27563824/pediatric-hodgkin-lymphoma-biomarkers-drugs-and-clinical-trials-for-translational-science-and-medicine
#19
Poonam Nagpal, Mohamed R Akl, Nehad M Ayoub, Tatsunari Tomiyama, Tasheka Cousins, Betty Tai, Nicole Carroll, Themba Nyrenda, Pritish Bhattacharyya, Michael B Harris, Andre Goy, Andrew Pecora, K Stephen Suh
Hodgkin lymphoma (HL) is a lymphoid malignancy that is typically derived from germinal-center B cells. EBV infection, mutations in NF-κB pathway genes, and genetic susceptibility are known risk factors for developing HL. CD30 and NF-κB have been identified as potential biomarkers in pediatric HL patients, and these molecules may represent therapeutic targets. Although current risk adapted and response based treatment approaches yield overall survival rates of >95%, treatment of relapse or refractory patients remains challenging...
August 22, 2016: Oncotarget
https://www.readbyqxmd.com/read/27535974/adct-301-a-pyrrolobenzodiazepine-pbd-dimer-containing-antibody-drug-conjugate-adc-targeting-cd25-expressing-hematological-malignancies
#20
Michael Flynn, Francesca Zammarchi, Peter C Tyrer, Ayse U Akarca, Narinder Janghra, Charles E Britten, Carin Eg Havenith, Jean-Noel Levy, Arnaud Tiberghien, Luke A Masterson, Conor Barry, Francois d'Hooge, Teresa Marafioti, Paul Whi Parren, David G Williams, Philip W Howard, Patrick H van Berkel, John A Hartley
Despite the many advances in the treatment of hematological malignancies over the past decade, outcomes in refractory lymphomas remain poor. One potential strategy in this patient population is the specific targeting of IL-2R-α (CD25), which is over-expressed on many lymphoma and leukemic cells, using antibody drug conjugates (ADCs). ADCT-301 is an ADC composed of human IgG1 HuMax®-TAC against CD25, stochastically conjugated through a dipeptide cleavable linker to a pyrrolobenzodiazepine (PBD) dimer warhead with a drug-antibody ratio (DAR) of 2...
August 17, 2016: Molecular Cancer Therapeutics
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