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anti pd 1 melanoma

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https://www.readbyqxmd.com/read/28324889/evaluation-of-clinicopathological-factors-in-pd-1-response-derivation-and-validation-of-a-prediction-scale-for-response-to-pd-1-monotherapy
#1
Adi Nosrati, Katy K Tsai, Simone M Goldinger, Paul Tumeh, Barbara Grimes, Kimberly Loo, Alain P Algazi, Thi Dan Linh Nguyen-Kim, Mitchell Levesque, Reinhard Dummer, Omid Hamid, Adil Daud
BACKGROUND: Anti-PD-1 therapy has shown significant clinical activity in advanced melanoma. We developed and validated a clinical prediction scale for response to anti- PD-1 monotherapy. METHODS: A total of 315 patients with advanced melanoma treated with pembrolizumab (2 or 10 mg kg(-1) Q2W or Q3W) or nivolumab (3 mg kg(-1) Q2W) at four cancer centres between 2011 to 2013 served as the setting for the present cohort study. Variables with significant association to response on a univariate analysis were entered into a forward stepwise logistic regression model and were given a score based on ORs to calculate a clinical prediction scale...
March 21, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/28324885/reply-to-comment-on-efficacy-and-toxicity-of-treatment-with-the-anti-ctla-4-antibody-ipilimumab-in-patients-with-metastatic-melanoma-after-prior-anti-pd-1-therapy
#2
Samantha Bowyer, Prashanth Prithviraj, Paul Lorigan, James Larkin, Grant McArthur, Victoria Atkinson, Michael Millward, Muoi Khou, Stefan Diem, Sangeetha Ramanujam, Ben Kong, Elizabeth Liniker, Alexander Guminski, Phillip Parente, Miles C Andrews, Sagun Parakh, Jonathan Cebon, Georgina V Long, Matteo S Carlino, Oliver Klein
No abstract text is available yet for this article.
March 21, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/28324884/comment-on-efficacy-and-toxicity-of-treatment-with-the-anti-ctla-4-antibody-ipilimumab-in-patients-with-metastatic-melanoma-after-prior-anti-pd-1-therapy
#3
Keisuke Imafuku, Koji Yoshino, Kei Yamaguchi, Satoshi Tsuboi, Kuniaki Ohara, Hiroo Hata
No abstract text is available yet for this article.
March 21, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/28323504/pembrolizumab-use-for-the-treatment-of-advanced-melanoma
#4
Pol Specenier
Until recently, overall long term survival in patients with stage IV melanoma was lower than 10 %. However, the treatment of melanoma has evolved rapidly over the last few years, with the advent of inhibitors of BRAF and MEK and of immunotherapeutic agents including ipilimumab, nivolumab, and pembrolizumab. Areas covered: This is a comprehensive review of the literature on the role of pembrolizumab in melanoma. Pembrolizumab is a Programmed Death Receptor 1 (PD-1) directed monoclonal antibody which is approved by FDA and EMA for the treatment of patients with metastatic melanoma...
March 21, 2017: Expert Opinion on Biological Therapy
https://www.readbyqxmd.com/read/28314298/multi-omics-profiling-of-patients-with-melanoma-treated-with-nivolumab-in-project-hope
#5
Shusuke Yoshikawa, Yoshio Kiyohara, Masaki Otsuka, Ryota Kondou, Chizu Nonomura, Haruo Miyata, Akira Iizuka, Keiichi Ohshima, Kenichi Urakami, Takeshi Nagashima, Masatoshi Kusuhara, Takashi Sugino, Tohru Mochizuki, Ken Yamaguchi, Yasuto Akiyama
BACKGROUND: Project HOPE (High-tech Omics-based Patient Evaluation) has been in progress since 2014 and uses whole-exome sequencing (WES) and gene expression profiling (GEP). Among a total of 1,685 patients with cancer, 13 with melanoma were registered and characterized using multi-omics analyses to investigate specific biomarkers in responders to programmed cell death-1 (PD-1) blockade. MATERIALS AND METHODS: The patients with melanoma comprised of six males and seven females, and their mean age was 68 years...
March 2017: Anticancer Research
https://www.readbyqxmd.com/read/28301259/novel-treatment-of-melanoma-combined-parasite-derived-peptide-gk-1-and-anti-programmed-death-ligand-1-therapy
#6
Jesus Vera-Aguilera, Armando Perez-Torres, Diego Beltran, Cynthia Villanueva-Ramos, Mitchell Wachtel, Eduardo Moreno-Aguilera, Carlos Vera-Aguilera, Gary Ventolini, Raul Martínez-Zaguilán, Souad R Sennoune
Recent successes in the development of new therapies for metastatic melanoma, such as mitogen-activated protein kinase pathway inhibitors, anticytotoxic T lymphocyte-associated antigen-4, and programmed cell death protein 1/programmed cell death ligand 1 (PD-L1) pathway-blocking antibodies, as well as combination strategies, all yielded promising results, changing the continually evolving landscape of therapeutic options for patients with melanoma. One promising new treatment modality is based on the use of immunomodulatory monoclonal antibodies that enhance the function of components of the antitumor immune response such as T cells or block immunologic checkpoints that restrain effective antitumor immunity...
March 2017: Cancer Biotherapy & Radiopharmaceuticals
https://www.readbyqxmd.com/read/28295707/anti-pd-1-pd-l1-induced-psoriasis-from-an-oncological-perspective
#7
Juan Ruiz-Bañobre, Jorge García-González
We read with interest the letter to the editor by Bonigen et al(1) regarding the development of psoriasis during anti-programed cell death protein 1 (PD-1) therapy. The authors describe a series of 17 patients diagnosed with melanoma or lung cancer treated with anti-PD-1 drugs in first line or later. In the final analysis, they also include 4 patients previously described in the literature. This article is protected by copyright. All rights reserved.
March 10, 2017: Journal of the European Academy of Dermatology and Venereology: JEADV
https://www.readbyqxmd.com/read/28286532/efficacy-of-juzentaihoto-for-tumor-immunotherapy-in-b16-melanoma-metastasis-model
#8
Shintaro Ishikawa, Takako Ishikawa, Chiaki Tezuka, Kazuhito Asano, Masataka Sunagawa, Tadashi Hisamitsu
Introduction. Medical care for Japanese cancer patients includes Western and Kampo medicines, and treatments with juzentaihoto (JTT) reportedly prevent cancer metastasis and recurrence. In this study, we examined the effects of JTT on natural killer (NK) cell activity and metastasis in combined treatments with anti-PD-1 antibody in a mouse model of melanoma metastasis. Methods. C57BL/6 male mice were intravenously injected with B16 melanoma cells (B16 cell) and were given chow containing 3% JTT. In subsequent in vivo experiments, we assessed serum cytokine levels and tumor colony formation in the lungs...
2017: Evidence-based Complementary and Alternative Medicine: ECAM
https://www.readbyqxmd.com/read/28283736/phase-1b-study-of-pembrolizumab-mk-3475-anti-pd-1-monoclonal-antibody-in-japanese-patients-with-advanced-melanoma-keynote-041
#9
Naoya Yamazaki, Tatsuya Takenouchi, Manabu Fujimoto, Hironobu Ihn, Hiroshi Uchi, Takashi Inozume, Yoshio Kiyohara, Hisashi Uhara, Kazuhiko Nakagawa, Hiroshi Furukawa, Hidefumi Wada, Kazuo Noguchi, Takashi Shimamoto, Kenji Yokota
PURPOSE: This phase I b study evaluated the safety and anti-tumor activity of pembrolizumab in Japanese patients with advanced melanoma. METHODS: Pembrolizumab (2 mg/kg) was given every 3 weeks (Q3W) for up to 2 years or until confirmed progression or unacceptable toxicity. The tumor response was assessed as per the Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) by both investigator review and central review. RESULTS: Forty-two patients with advanced melanoma received pembrolizumab...
March 11, 2017: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/28275910/mechanisms-of-drug-resistance-in-melanoma
#10
Matthew Winder, Amaya Virós
Metastatic melanoma is associated with poor outcome and is largely refractory to the historic standard of care. In recent years, the development of targeted small-molecule inhibitors and immunotherapy has revolutionised the care and improved the overall survival of these patients. Therapies targeting BRAF and MEK to block the mitogen-activated protein kinase (MAPK) pathway were the first to show unprecedented clinical responses. Following these encouraging results, antibodies targeting immune checkpoint inhibition molecules cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4), programmed cell death (PD)-1, and PD-ligand1(PD-L1) demonstrated sustained tumour regression in a significant subset of patients by enabling an anti-tumour immunologic response...
March 9, 2017: Handbook of Experimental Pharmacology
https://www.readbyqxmd.com/read/28272463/pd-1-inhibitors-increase-the-incidence-and-risk-of-pneumonitis-in-cancer-patients-in-a-dose-independent-manner-a-meta-analysis
#11
Jiaying Wu, Dongsheng Hong, Xiangnan Zhang, Xiaoyang Lu, Jing Miao
Therapies that targeted PD-1 have shown remarkable rates of durable clinical responses in patients with various tumor types. However, the extent and knowledge of pulmonary toxicities associated with PD-1 blockade, mainly manifested as pneumonitis, remains obscure. In this study, a total of 6360 subjects from 16 phase II/III clinical trials were pooled for meta-analysis to evaluate the overall incidence and risk of PD-1 inhibitors-related pneumonitis in cancer patients. The incidence of pneumonitis during anti-PD-1 immunotherapy was 2...
March 8, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28258697/tim-3-and-its-role-in-regulating-anti-tumor-immunity
#12
REVIEW
Madhumita Das, Chen Zhu, Vijay K Kuchroo
Immunotherapy is being increasingly recognized as a key therapeutic modality to treat cancer and represents one of the most exciting treatments for the disease. Fighting cancer with immunotherapy has revolutionized treatment for some patients and therapies targeting the immune checkpoint molecules such as CTLA-4 and PD-1 have achieved durable responses in melanoma, renal cancer, Hodgkin's diseases and lung cancer. However, the success rate of these treatments has been low and a large number of cancers, including colorectal cancer remain largely refractory to CTLA-4 and PD-1 blockade...
March 2017: Immunological Reviews
https://www.readbyqxmd.com/read/28256716/assessing-microenvironment-immunogenicity-using-tumor-specimen-exomes-co-detection-of-tcr-%C3%AE-%C3%AE-v-d-j-recombinations-correlates-with-pd-1-expression
#13
Yaping N Tu, Wei Lue Tong, Mohammad D Samy, John M Yavorski, Minjung Kim, George Blanck
T-cell receptor (TcR) recombinations can be recovered from tumor specimen, whole exome (WXS) files. However, it is not yet clear how these recombinations represent lymphocytes or an anti-tumor immune response. Here we report the identification of productive TcR-β recombinations in WXS files representing primary and metastatic melanoma. The recombinations are identifiable in about 20% of the cancer genome atlas melanoma samples. This frequency of detection is lower than the frequency of TcR-α VJ recombinations, consistent with the occurrence of biallelic TcR-α recombinations and possibly consistent with fact that only one junctional recombination is required for TcR-α whereas two recombinations are required to form a TcR-β gene...
March 3, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/28252315/checkpoint-blockade-in-lung-cancer-and-mesothelioma
#14
Lysanne A Lievense, Daniel H Sterman, Robin Cornelissen, Joachim G Aerts
In the past decade, immunotherapy has emerged as a new treatment modality in cancer. The most success has been achieved with the class of checkpoint inhibitors; antibodies which unleash the anti-tumor immune response. Following the success in melanoma, numerous clinical trials are being conducted investigating checkpoint inhibitors in lung cancer and mesothelioma. The programmed death protein 1-protein death ligand 1/2 (PD-1 - PD-L1/2) pathway and cytotoxic T-lymphocyte associated protein 4 (CTLA4) are currently the most studied immunotherapeutic targets in these malignancies...
March 2, 2017: American Journal of Respiratory and Critical Care Medicine
https://www.readbyqxmd.com/read/28247187/development-of-novel-immunopet-tracers-to-image-human-pd-1-checkpoint-expression-on-tumor-infiltrating-lymphocytes-in-a-humanized-mouse-model
#15
Arutselvan Natarajan, Aaron T Mayer, Robert E Reeves, Claude M Nagamine, Sanjiv Sam Gambhir
PURPOSE: It is well known that cancers exploit immune checkpoints (programmed death 1 receptor (PD-1) and its ligand (PD-L1)) to evade anti-tumor immune responses. Although immune checkpoint (IC) blockade is a promising approach, not all patients respond. Hence, imaging of tumor-infiltrating lymphocytes (TILs) is of high specific interest, as they are known to express PD-1 during activation and subsequent exhaustion in the tumor microenvironment and are thought to be potentially predictive of therapeutic responses to IC blockade...
February 28, 2017: Molecular Imaging and Biology: MIB: the Official Publication of the Academy of Molecular Imaging
https://www.readbyqxmd.com/read/28239466/nivolumab-induced-myxedema-crisis
#16
Uqba Khan, Humaira Rizvi, Dahlia Sano, Jane Chiu, Tarik Hadid
BACKGROUND: Nivolumab is an anti-programmed cell death (anti-PD-1) monoclonal antibody that is approved by Food and Drug Administration for treatment of metastatic non-small cell lung cancer, metastatic melanoma, relapsed Hodgkin lymphoma and advanced renal cell cancer. We report a rare case of myxedema crisis induced by nivolumab in a patient with metastatic squamous cell carcinoma of lung. CASE PRESENTATION: Fifty three-year old woman with metastatic squamous cell carcinoma currently on treatment with nivolumab presented with diffuse facial and tongue swelling, slurred speech, depressed mentation, fatigue and weakness...
2017: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/28239462/thrombocytopenia-in-patients-with-melanoma-receiving-immune-checkpoint-inhibitor-therapy
#17
Eileen Shiuan, Kathryn E Beckermann, Alpaslan Ozgun, Ciara Kelly, Meredith McKean, Jennifer McQuade, Mary Ann Thompson, Igor Puzanov, John P Greer, Suthee Rapisuwon, Michael Postow, Michael A Davies, Zeynep Eroglu, Douglas Johnson
BACKGROUND: Immune checkpoint inhibitors, including antibodies against programmed death 1 (PD-1) and cytotoxic T-lymphocyte antigen 4 (CTLA-4), are being used with increasing frequency for the treatment of cancer. Immune-related adverse events (irAEs) including colitis, dermatitis, and pneumonitis are well described, but less frequent events are now emerging with larger numbers of patients treated. Herein we describe the incidence and spectrum of thrombocytopenia following immune checkpoint inhibitor therapy and two severe cases of idiopathic thrombocytopenic purpura (ITP)...
2017: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/28230715/a-multireferral-centre-retrospective-cohort-analysis-on-the-experience-in-treatment-of-metastatic-uveal-melanoma-and-utilization-of-sequential-liver-directed-treatment-and-immunotherapy
#18
Malinda Itchins, Paolo A Ascierto, Alexander M Menzies, Meredith Oatley, Serigne Lo, Dariush Douraghi-Zadeh, Timmothy Harrington, Richard Maher, Antonio M Grimaldi, Alexander Guminski
Metastatic uveal melanoma is a rare malignancy with a poor prognosis. To date, systemic therapy has been ineffective; however, there are few data on the benefits of anti-CTLA4 or anti-PD-1 antibodies in sequence with liver-directed therapy. A retrospective cohort analysis was carried out on 37 consecutive patients managed in a tertiary referral centre examining the safety and efficacy of treatment; patterns of care; and impact on survival. The sequential treatment with transarterial chemotherapy (TAC), systemic immunotherapy (IT) and systemic chemotherapy was reviewed...
February 22, 2017: Melanoma Research
https://www.readbyqxmd.com/read/28222231/two-cases-of-anti-programmed-cell-death-1-associated-bullous-pemphigoid-like-disease-and-eruptive-keratoacanthomas-featuring-combined-histopathology
#19
Justin P Bandino, David M Perry, Christina E Clarke, Richard M Marchell, Dirk M Elston
Programmed cell death protein 1 (PD-1) inhibitors (pembrolizumab, nivolumab) are novel immunotherapies revolutionizing the management of advanced malignancy with an improved adverse effect profile, yet the immune-related side effects are still being characterized.(1,2) We report the unique concurrence of bullous pemphigoid-like disease (BP) with keratoacanthomas and squamous cell carcinomas in two patients receiving anti-PD-1 immunotherapy for metastatic melanoma. This article is protected by copyright. All rights reserved...
February 21, 2017: Journal of the European Academy of Dermatology and Venereology: JEADV
https://www.readbyqxmd.com/read/28214657/ipilimumab-alone-or-in-combination-with-nivolumab-after-progression-on-anti-pd-1-therapy-in-advanced-melanoma
#20
Lisa Zimmer, Susmitha Apuri, Zeynep Eroglu, Lisa A Kottschade, Andrea Forschner, Ralf Gutzmer, Max Schlaak, Lucie Heinzerling, Angela M Krackhardt, Carmen Loquai, Svetomir N Markovic, Richard W Joseph, Kelly Markey, Jochen S Utikal, Carsten Weishaupt, Simone M Goldinger, Vernon K Sondak, Jonathan S Zager, Dirk Schadendorf, Nikhil I Khushalani
BACKGROUND: The anti-programmed cell death-1 (PD-1) inhibitors pembrolizumab and nivolumab alone or in combination with ipilimumab have shown improved objective response rates and progression-free survival compared to ipilimumab only in advanced melanoma patients. Anti-PD-1 therapy demonstrated nearly equal clinical efficacy in patients who had progressed after ipilimumab or were treatment-naïve. However, only limited evidence exists regarding the efficacy of ipilimumab alone or in combination with nivolumab after treatment failure to anti-PD-therapy...
February 16, 2017: European Journal of Cancer
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