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https://www.readbyqxmd.com/read/29685160/advances-in-cd30-and-pd-1-targeted-therapies-for-classical-hodgkin-lymphoma
#1
REVIEW
Yucai Wang, Grzegorz S Nowakowski, Michael L Wang, Stephen M Ansell
CD30 and programmed cell death protein 1 (PD-1) are two ideal therapeutic targets in classical Hodgkin lymphoma (cHL). The CD30 antibody-drug conjugate (ADC) brentuximab vedotin and the PD-1 antibodies nivolumab and pembrolizumab are highly efficacious in treating relapsed and/or refractory cHL. Ongoing studies are evaluating their efficacy in earlier lines of therapy and have demonstrated encouraging results. These agents are expected to further change the landscape of cHL management. Increased cure rates and reduced long-term toxicity from traditional chemotherapy and radiotherapy are likely with the emergence of these novel targeted therapies...
April 23, 2018: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/29680236/chimeric-small-antibody-fragments-as-strategy-to-deliver-therapeutic-payloads
#2
Sandra Aguiar, Joana Dias, Ana M Manuel, Roberto Russo, Pedro M P Gois, Frederico A da Silva, Joao Goncalves
Antibody-drug conjugates (ADCs) represent an innovative class of biopharmaceuticals, which aim at achieving a site-specific delivery of cytotoxic agents to the target cell. The use of ADCs represents a promising strategy to overcome the disadvantages of conventional pharmacotherapy of cancer or neurological diseases, based on cytotoxic or immunomodulatory agents. ADCs consist of monoclonal antibodies attached to biologically active drugs by means of cleavable chemical linkers. Advances in technologies for the coupling of antibodies to cytotoxic drugs promise to deliver greater control of drug pharmacokinetic properties and to significantly improve pharmacodelivery applications, minimizing exposure of healthy tissue...
2018: Advances in Protein Chemistry and Structural Biology
https://www.readbyqxmd.com/read/29614535/-hodgkin-lymphoma-update-2018
#3
Michael Fuchs
Hodgkin Lymphoma is one of the best curable tumor in adults. PET adapted therapy with BEACOPPescalated is standard for 1st line treatment of advanced stage disease and the majority of patient can be sufficiently treated with 4 cycles of BEACOPPescalated only. Maintenance therapy after autologous stem cell transplantation with Brentuximab Vedotin was recently introduced. PD-1 inhibitors such as Nivolumab and Pembrolizumab were approved for the treatment of relapsed Hodgkin Lymphoma after Brentuximab Vedotin...
April 2018: Deutsche Medizinische Wochenschrift
https://www.readbyqxmd.com/read/29611187/tandem-haematopoietic-stem-cell-transplantation-for-high-risk-relapsed-refractory-hodgkin-lymphoma-a-lysa-study
#4
Benedicte Deau, Sandy Amorim, Aurore Perrot, Philippe Quittet, Jerome Cornillon, Driss Chaoui, Jean P Marolleau, Lucie Oberic, Katell Le Du, Luc-Matthieu Fornecker, Olivier Tournilhac, Anne S Veillard, Isabelle Chaillol, Marie Robin, Jérôme Tamburini, Pauline Brice
Tandem stem cell transplantation (SCT) is an option for high-risk relapsed/refractory Hodgkin Lymphoma (HL) patients. We evaluated the tolerance/efficacy of double autologous or autologous SCT (ASCT) followed by allogenic SCT (alloSCT) in 120 HL patients prospectively registered on a French nationwide database. Median age was 26 (14-56) years. Complete remission rate was 60%, including 33% after a single line, and another 27% after two or more salvage regimens. Partial response rate was 32%, and 8% suffered treatment failure...
April 2, 2018: British Journal of Haematology
https://www.readbyqxmd.com/read/29584546/nivolumab-for-relapsed-refractory-classic-hodgkin-lymphoma-after-failure-of-autologous-hematopoietic-cell-transplantation-extended-follow-up-of-the-multicohort-single-arm-phase-ii-checkmate-205-trial
#5
Philippe Armand, Andreas Engert, Anas Younes, Michelle Fanale, Armando Santoro, Pier Luigi Zinzani, John M Timmerman, Graham P Collins, Radhakrishnan Ramchandren, Jonathon B Cohen, Jan Paul De Boer, John Kuruvilla, Kerry J Savage, Marek Trneny, Margaret A Shipp, Kazunobu Kato, Anne Sumbul, Benedetto Farsaci, Stephen M Ansell
Purpose Genetic alterations causing overexpression of programmed death-1 ligands are near universal in classic Hodgkin lymphoma (cHL). Nivolumab, a programmed death-1 checkpoint inhibitor, demonstrated efficacy in relapsed/refractory cHL after autologous hematopoietic cell transplantation (auto-HCT) in initial analyses of one of three cohorts from the CheckMate 205 study of nivolumab for cHL. Here, we assess safety and efficacy after extended follow-up of all three cohorts. Methods This multicenter, single-arm, phase II study enrolled patients with relapsed/refractory cHL after auto-HCT treatment failure into cohorts by treatment history: brentuximab vedotin (BV)-naïve (cohort A), BV received after auto-HCT (cohort B), and BV received before and/or after auto-HCT (cohort C)...
March 27, 2018: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/29578307/rapid-and-simultaneous-quantification-of-a-mixture-of-biopharmaceuticals-by-a-liquid-chromatography-quadrupole-time-of-flight-mass-spectrometric-method-in-rat-plasma-following-cassette-dosing
#6
Min-Ho Park, Jin-Ju Byeon, Seok-Ho Shin, Nahye Kim, Yuri Park, Byeong Ill Lee, Jangmi Choi, Young G Shin
RATIONALE: Cassette dosing technique is a technique that administers various drugs to a single animal at once and quantitated simultaneously. The purpose of this study was to evaluate the feasibility of cassette dosing as a means of increasing throughput and decreasing animal usage for pharmacokinetic studies of biopharmaceuticals using LC-TOF-MS analysis. METHOD: Brentuximab, trastuzumab, cetuximab and adalimumab were used as model biopharmaceuticals. The method consisted of immunoprecipitation followed by tryptic digestion for sample preparation and LC-TOF-MS analysis of specific signature peptides in the positive ion mode using electrospray ionization...
March 26, 2018: Rapid Communications in Mass Spectrometry: RCM
https://www.readbyqxmd.com/read/29572070/escmid-study-group-for-infections-in-compromised-hosts-esgich-consensus-document-on-the-safety-of-targeted-and-biological-therapies-an-infectious-diseases-perspective-agents-targeting-lymphoid-or-myeloid-cells-surface-antigens-ii-cd22-cd30-cd33-cd38-cd40-slamf
#7
REVIEW
Lubos Drgona, Carlota Gudiol, Simone Lanini, Bernd Salzberger, Giuseppe Ippolito, Małgorzata Mikulska
BACKGROUND: The present review is part of the ESCMID Study Group for Infections in Compromised Hosts (ESGICH) Consensus Document on the safety of targeted and biological therapies. AIMS: To review, from an Infectious Diseases perspective, the safety profile of agents targeting CD22, CD30, CD33, CD38, CD40, SLAMF-7 and CCR4 and to suggest preventive recommendations. SOURCES: Computer-based MEDLINE searches with MeSH terms pertaining to each agent or therapeutic family...
March 20, 2018: Clinical Microbiology and Infection
https://www.readbyqxmd.com/read/29552279/brentuximab-vedotin-targeting-cd30-as-standard-in-ctcl
#8
EDITORIAL
H Miles Prince, Ashish Gautam, Youn H Kim
No abstract text is available yet for this article.
February 23, 2018: Oncotarget
https://www.readbyqxmd.com/read/29538040/managing-seminomatous-and-nonseminomatous-germ-cell-tumors
#9
Jad Chahoud, Miao Zhang, Amishi Shah, Sue-Hwa Lin, Louis L Pisters, Shi-Ming Tu
PURPOSE OF REVIEW: In the present review, we summarize the recent developments in the management of germ cell tumors (GCTs). RECENT FINDINGS: Treatment-related acute and late-onset toxicity remains a key challenge in the management of GCTs, with recent evidence showing that the adverse health outcomes of etoposide and cisplatin for four cycles in comparison to bleomycin, etoposide, and cisplatin for three cycles appear to be similar. Recent data showed that multidisciplinary clinic approach and management in experienced academic centers were associated with improved overall survival in GCT patients...
May 2018: Current Opinion in Oncology
https://www.readbyqxmd.com/read/29537283/noninvasive-trafficking-of-brentuximab-vedotin-and-pet-imaging-of-cd30-in-lung-cancer-murine-models
#10
Lei Kang, Dawei Jiang, Emily B Ehlerding, Todd E Barnhart, Dalong Ni, Jonathan W Engle, Rongfu Wang, Peng Huang, Xiaojie Xu, Weibo Cai
CD30 has been considered a unique diagnostic and therapeutic target for CD30-positive lymphomas and some lung diseases. Additionally, CD30 has shown high expression in clinical lung cancer samples. In this study,89 Zr-radiolabeled Brentuximab vedotin (BV) was developed for in vivo tracking of BV and imaging CD30 expression in lung cancer models via conjugation with desferrioxamine (Df). CD30 expression in three lung cancer cell lines (H460, H358, and A549) was quantified by Western blot. Flow cytometry and saturation binding assays were used to evaluate the binding capabilities of the tracer in vitro...
March 14, 2018: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/29526961/choledochoduodenal-fistula-during-chemotherapy-with-brentuximab-vedotin-for-methotrexate-associated-lymphoproliferative-disorder
#11
Yuji Eso, Norimitsu Uza, Kotaro Shirakawa, Kenji Sawada, Kentaro Katsuragi, Minoru Matsuura, Hiroshi Seno
We herein report a patient with a history of rheumatoid arthritis treated with methotrexate, which caused methotrexate-associated lymphoproliferative disorder and obstructive jaundice due to an enlarged lymph node. The obstructive jaundice was treated with endoscopic biliary stenting. A histopathological examination revealed features of Hodgkin's lymphoma, and chemotherapy with brentuximab vedotin was administered. Cholangiography and duodenoscopy after four rounds of chemotherapy revealed a choledochoduodenal fistula that developed in response to chemotherapy...
March 9, 2018: Internal Medicine
https://www.readbyqxmd.com/read/29521140/current-and-emerging-treatment-options-for-a-patient-with-a-second-relapse-of-hodgkin-s-lymphoma
#12
Avyakta Kallam, James O Armitage
Hodgkin's lymphoma (HL) is largely a curable disease with excellent prognosis. The standard of care in patients with relapsed disease has been to try salvage chemotherapy followed by an autologous stem cell transplantation (ASCT). Managing the patients who relapse after ASCT, is challenging. With the approval of targeted therapies such as PD-1 inhibitors, brentuximab vedotin, the outcomes have improved greatly. Areas covered: This review summarizes the current data available on the newer therapies as well as the present strategies used to treat patients with relapsed HL after an autologous stem cell transplantation...
March 9, 2018: Expert Review of Hematology
https://www.readbyqxmd.com/read/29516333/update-on-the-treatment-of-anaplastic-large-cell-lymphoma
#13
REVIEW
Khoan Vu, Weiyun Ai
PURPOSE OF REVIEW: Given the rarity of anaplastic large cell lymphoma (ALCL), studies evaluating new therapies have typically grouped ALCL together with other peripheral T cell lymphomas (PTCL). Thus, the treatment paradigm for ALCL largely mirrors that of PTCL in general. In this review, we discuss the current standard of care as well as emerging therapies, including antibody-based drugs, in systemic ALCL as well as primary cutaneous and breast implant-associated ALCL. RECENT FINDINGS: High CD30 expression in ALCL has allowed the use of brentuximab vedotin, an anti-CD30 antibody-drug conjugate, in both systemic and primary cutaneous ALCL...
April 2018: Current Hematologic Malignancy Reports
https://www.readbyqxmd.com/read/29515072/-long-term-administration-of-brentuximab-vedotin-in-a-patient-with-primary-cutaneous-anaplastic-large-cell-lymphoma-with-peripheral-blood-involvement-with-leukemic-change
#14
Hanae Kumekawa, Daisuke Mizuchi, Mitsuko Iiyama
We report a case of long-term administration of brentuximab vedotin (BV) for primary cutaneous anaplastic large cell lymphoma (pc-ALCL) with leukemic change. A 67-year-old man with lymphadenopathy was admitted to our hospital. Six years ago, he was diagnosed with pc-ALCL at another hospital, and complete remission was achieved with radiation therapy. We performed a biopsy of his lymph node and diagnosed the recurrence of pc-ALCL with leukemic change. Initially, CHOP and GCD regimens were ineffective; however, partial remission was achieved following BV therapy...
2018: [Rinshō Ketsueki] the Japanese Journal of Clinical Hematology
https://www.readbyqxmd.com/read/29512859/cns-progression-during-vinblastine-or-targeted-therapies-for-high-risk-relapsed-alk-positive-anaplastic-large-cell-lymphoma-a-case-series
#15
Stephanie Ruf, Holger Hebart, Lisa Lyngsie Hjalgrim, Edita Kabickova, Peter Lang, Daniel Steinbach, Georg C Schwabe, Wilhelm Woessmann
Vinblastine and targeted therapies induce remissions in patients with relapsed or progressive anaplastic lymphoma kinase (ALK)-positive anaplastic large cell lymphoma (ALCL). Central nervous system (CNS) prophylaxis often is not included during re-induction in CNS-negative relapse patients. We report on five patients with progressive or early relapsed ALK-positive ALCL who developed CNS progression during re-induction with vinblastine, crizotinib, or brentuximab vedotin given for bridging to allogeneic blood stem cell transplantation...
March 7, 2018: Pediatric Blood & Cancer
https://www.readbyqxmd.com/read/29512830/tumor-stage-mycosis-fungoides-in-palmoplantar-localization-with-large-cell-transformation-and-partial-cd30-expression-shows-complete-response-to-brentuximab-vedotin
#16
A Khoa Pham, Joi B Carter, Nora R Ratcliffe, Alexander D Fuld, Frederick Lansigan, Nancy J Burnside, Marshall A Guill, Kathryn A Zug, Lesley A Jarvis, Robert E LeBlanc
Mycosis fungoides in palmoplantar localization (MFPP) is a rare variant of MF that is confined to the hands and feet. Patients commonly receive treatment over many years for suspected palmoplantar dermatitis before the diagnosis is made. Most MFPP patients remain at patch or plaque stage, and often respond to treatment with radiotherapy. Herein we describe a 77-year-old man who suffered 6 years of hand and foot dermatitis that failed multiple treatments, most notably TNF-α inhibitors and mycophenolate mofetil...
March 7, 2018: Journal of Cutaneous Pathology
https://www.readbyqxmd.com/read/29507077/five-year-outcomes-for-frontline-brentuximab-vedotin-with-chp-for-cd30-expressing-peripheral-t-cell-lymphomas
#17
Michelle A Fanale, Steven M Horwitz, Andres Forero-Torres, Nancy L Bartlett, Ranjana H Advani, Barbara Pro, Robert W Chen, Andrew Davies, Tim Illidge, Mayur Uttarwar, Shih-Yuan Lee, Hong Ren, Dana A Kennedy, Andrei R Shustov
This phase 1 study evaluated frontline brentuximab vedotin in combination with cyclophosphamide, doxorubicin, and prednisone (BV+CHP; 6 cycles, then up to 10 cycles of brentuximab vedotin monotherapy) in 26 patients with CD30-positive peripheral T-cell lymphoma, including 19 with systemic anaplastic large cell lymphoma. All patients (100%) achieved an objective response, with a complete remission rate of 92%, and none received a consolidative stem cell transplant. After a median observation period of 59.6 months (range, 4...
March 5, 2018: Blood
https://www.readbyqxmd.com/read/29500174/balancing-risk-and-benefit-in-early-stage-classical-hodgkin-lymphoma
#18
REVIEW
Paul J Bröckelmann, Stephanie Sasse, Andreas Engert
With defined chemotherapy and radiotherapy (RT) and risk-adapted treatment, early-stage classical Hodgkin lymphoma (HL) has become curable in a majority of patients. Hence, a major current goal is to reduce treatment-related toxicity while maintaining long-term disease control. Patients with early-stage favorable disease (ie, limited stage without risk factors [RFs]) are frequently treated with 2 cycles of doxorubicin, bleomycin, vinblastine, and dacarbazine (2×ABVD) followed by 20-Gy involved-field or involved-site RT (IF/ISRT)...
April 12, 2018: Blood
https://www.readbyqxmd.com/read/29500171/management-of-relapsed-refractory-classical-hodgkin-lymphoma-in-transplant-ineligible-patients
#19
Neha Mehta-Shah, Nancy L Bartlett
Addition of brentuximab vedotin, a CD30 targeted antibody-drug conjugate, and the PD-1 inhibitors, nivolumab and pembrolizumab, to the armamentarium for transplant-ineligible relapsed/refractory classical Hodgkin lymphoma has resulted in improved outcomes, including the potential for cure in a small minority of patients. For patients who have failed prior transplant or are unsuitable for dose-intense approaches based on age or comorbidities, an individualized approach with sequential use of single agents such as brentuximab vedotin, PD-1 inhibitors, everolimus, lenalidomide, or conventional agents such as gemcitabine or vinorelbine, may result in prolonged survivals with minimal or modest effect on quality of life...
March 2, 2018: Blood
https://www.readbyqxmd.com/read/29499935/targeted-delivery-of-auristatin-modified-toxins-to-pancreatic-cancer-using-aptamers
#20
Christina Kratschmer, Matthew Levy
Pancreatic cancer is one of the most lethal malignancies. Treatment with the first-line agent, gemcitabine, is often unsuccessful because it, like other traditional chemotherapeutic agents, is non-specific, resulting in off-target effects that necessitate administration of subcurative doses. Alternatively, monomethyl auristatin E (MMAE) and monomethyl auristatin F (MMAF) are highly toxic small molecules that require ligand-targeted delivery. MMAE has already received FDA approval as a component of an anti-CD30 antibody-drug conjugate, brentuximab vedotin...
March 2, 2018: Molecular Therapy. Nucleic Acids
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