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https://www.readbyqxmd.com/read/28522460/soluble-pd-l1-as-a-biomarker-in-malignant-melanoma-and-checkpoint-blockade
#1
Jun Zhou, Kathleen M Mahoney, Anita Giobbie-Hurder, Fengmin Zhao, Sandra Lee, Xiaoyun Liao, Scott Rodig, Jingjing Li, Xinqi Wu, Lisa H Butterfield, Matthias Piesche, Michael P Manos, Lauren M Eastman, Glenn Dranoff, Gordon J Freeman, F Stephen Hodi
Blockade of the pathway including Programmed death-ligand 1 (PD-L1) and its receptor Programmed cell death protein 1 (PD-1) has produced clinical benefits in patients with a variety of cancers.  Elevated levels of soluble PD-L1 (sPD-L1) have been associated with worse prognosis in renal cell carcinoma and multiple myeloma.  However, the regulatory roles and function of sPD-L1 particularly in connection with immune checkpoint blockade treatment are not fully understood.  We identified four splice variants of PD-L1 in melanoma cells, and all of them are secreted...
May 18, 2017: Cancer Immunology Research
https://www.readbyqxmd.com/read/28512666/diagnostic-efficacy-of-digital-dermoscopy-and-clinical-findings-in-thin-melanoma-of-the-lower-limbs
#2
Emi Dika, Marco Adriano Chessa, Simone Ribero, Pier A Fanti, Carlotta Gurioli, Martina Lambertini, Carlotta Baraldi, Annalisa Patrizi
The introduction of dermoscopy has improved the accuracy of diagnosis of melanoma. However, early stage melanoma can be difficult to diagnose. Eighty-nine cases of thin melanoma with a Breslow thickness ≤1 mm located on the lower limb and diagnosed between 2008 and 2016 were assessed using 4 dermoscopic algorithms: (i) modified pattern analysis; (ii) ABCD rule of dermoscopy; (iii) 7-point checklist; and (iv) Menzies' method. Two groups of early stage melanomas of the legs were identified: "difficult to diagnose melanomas" (DDM) and "non-difficult to diagnose melanomas" (NDDM)...
May 17, 2017: Acta Dermato-venereologica
https://www.readbyqxmd.com/read/28512174/dynamic-changes-in-pd-l1-expression-and-immune-infiltrates-early-during-treatment-predict-response-to-pd-1-blockade-in-melanoma
#3
Ricardo E Vilain, Alexander M Menzies, James S Wilmott, Hojabr Kakavand, Jason Madore, Alexander Guminski, Elizabeth Liniker, Ben Kong, Adam Cooper, Julie R Howle, Robyn P M Saw, Valerie Jakrot, Serigne Lo, John F Thompson, Matteo S Carlino, Richard F Kefford, Georgina V Long, Richard A Scolyer
Disruption of PD-L1/cytotoxic T-cell PD-1 signalling by immune-checkpoint inhibitors improves survival in cancer patients. This study sought to identify changes in tumoral PD-L1 expression and tumor-associated immune cell flux with anti-PD1 therapies in melanoma patients, particularly early during treatment, and correlate them with treatment response<br /><br />Experimental Design: Forty-six tumor biopsies from 23 unresectable AJCC Stage III/IV melanoma patients receiving pembrolizumab/nivolumab were analyzed...
May 16, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28509765/multicenter-real-life-experience-with-checkpoint-inhibitors-and-targeted-therapy-agents-in-advanced-melanoma-patients-in-switzerland
#4
Joanna Mangana, Phil F Cheng, Corina Kaufmann, Valerie C Amann, Anna L Frauchiger, Viola Stögner, Ulrike Held, Roger von Moos, Olivier Michielin, Ralph P Braun, Mitchell P Levesque, Simone M Goldinger, Reinhard Dummer
Metastatic melanoma is a highly aggressive disease. Recent progress in immunotherapy (IT) and targeted therapy (TT) has led to significant improvements in response and survival rates in metastatic melanoma patients. The current project aims to determine the benefit of the introduction of these new therapies in advanced melanoma across several regions of Switzerland. This is a retrospective multicenter analysis of 395 advanced melanoma patients treated with standard chemotherapy, checkpoint inhibitors, and kinase inhibitors from January 2008 until December 2014...
May 15, 2017: Melanoma Research
https://www.readbyqxmd.com/read/28506536/checkpoint-inhibition-and-melanoma-considerations-in-treating-the-older-adult
#5
REVIEW
Claire F Friedman, Jedd D Wolchok
The incidence of melanoma and associated mortality rate from advanced disease in older adults is increasing over time. Checkpoint inhibitors have demonstrated a survival benefit for the treatment of stage IV or unresectable stage III disease and have become one of the standards of care. Data suggests that adults aged 65 and older benefit from treatment with checkpoint inhibitors without an increased incidence in adverse events. However, clinicians should be aware of the potential side effects of this class of medications and how to manage them in older adults...
May 11, 2017: Journal of Geriatric Oncology
https://www.readbyqxmd.com/read/28499411/paraneoplastic-acral-vascular-syndrome-in-a-patient-with-metastatic-melanoma-under-immune-checkpoint-blockade
#6
Thilo Gambichler, Stefanie Strutzmann, Andrea Tannapfel, Laura Susok
BACKGROUND: Paraneoplastic acral vascular syndrome (PAVS) is a rare phenomenon which is observed in patients with adenocarcinomas and other malignancies. Various potential pathogenic mechanisms such as tumour invasion of sympathetic nerves, hyperviscosity, hypercoagulability, vasoactive tumour-secreted substances, and immunological mechanisms have been suggested. CASE PRESENTATION: We report a 60-year-old Caucasian male attended our hospital with a bulky lymph node mass in the right axilla...
May 12, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28475671/dabrafenib-plus-trametinib-versus-dabrafenib-monotherapy-in-patients-with-metastatic-braf-v600e-k-mutant-melanoma-long-term-survival-and-safety-analysis-of-a-phase-3-study
#7
G V Long, K T Flaherty, D Stroyakovskiy, H Gogas, E Levchenko, F de Braud, J Larkin, C Garbe, T Jouary, A Hauschild, V Chiarion-Sileni, C Lebbe, M Mandalà, M Millward, A Arance, I Bondarenko, J B A G Haanen, J Hansson, J Utikal, V Ferraresi, P Mohr, V Probachai, D Schadendorf, P Nathan, C Robert, A Ribas, M A Davies, S R Lane, J J Legos, B Mookerjee, J-J Grob
Background: Previous analysis of COMBI-d (NCT01584648) demonstrated improved progression-free survival (PFS) and overall survival (OS) with combination dabrafenib and trametinib versus dabrafenib monotherapy in BRAF V600E/K-mutant metastatic melanoma. This study was continued to assess 3-year landmark efficacy and safety after ≥36-month follow-up for all living patients. Patients and methods: This double-blind, phase 3 study enrolled previously untreated patients with BRAF V600E/K-mutant unresectable stage IIIC or stage IV melanoma...
May 5, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/28469417/plasma-microrna-levels-following-resection-of-metastatic-melanoma
#8
Nicholas Latchana, Zachary B Abrams, J Harrison Howard, Kelly Regan, Naduparambil Jacob, Paolo Fadda, Alicia Terando, Joseph Markowitz, Doreen Agnese, Philip Payne, William E Carson
Melanoma remains the leading cause of skin cancer-related deaths. Surgical resection and adjuvant therapies can result in disease-free intervals for stage III and stage IV disease; however, recurrence is common. Understanding microRNA (miR) dynamics following surgical resection of melanomas is critical to accurately interpret miR changes suggestive of melanoma recurrence. Plasma of 6 patients with stage III (n = 2) and stage IV (n = 4) melanoma was evaluated using the NanoString platform to determine pre- and postsurgical miR expression profiles, enabling analysis of more than 800 miRs simultaneously in 12 samples...
2017: Bioinformatics and Biology Insights
https://www.readbyqxmd.com/read/28457692/is-pregnancy-associated-melanoma-associated-with-adverse-outcomes
#9
Maris S Jones, Jihey Lee, Stacey L Stern, Mark B Faries
BACKGROUND: Melanoma is the most common malignancy encountered during pregnancy. Conflicting data have led to ongoing confusion regarding pregnancy-associated melanoma (PAM) in the media and among the public. The objective of this study was to better characterize both the clinical presentation of PAM and its prognostic implications. STUDY DESIGN: Female patients of reproductive age, with stage 0 to IV cutaneous melanoma, were identified from our prospectively maintained database...
March 23, 2017: Journal of the American College of Surgeons
https://www.readbyqxmd.com/read/28454272/dinitrophenyl-hapten-with-laser-immunotherapy-for-advanced-malignant-melanoma-a-clinical-study
#10
Dian-Jun Chen, Xiao-Song Li, Hui Zhao, Yan Fu, Huan-Rong Kang, Fang-Fang Yao, Jia Hu, Nan Qi, Huan-Huan Zhang, Nan Du, Wei-R Chen
The present study aimed to evaluate the efficacy and safety of in situ immunotherapy with dinitrophenyl (DNP) hapten in combination with laser therapy for patients with malignant melanoma (MM). Between February 2008 and March 2012, 72 patients with stage III or IV MM were enrolled. Patients received in situ DNP alone (n=32) or in combination with laser therapy (n=32), and each group received dacarbazine chemotherapy. The levels of peripheral cluster of differentiation (CD)4(+)CD25(+) regulatory T cells (Tregs), interleukin (IL)-10 and tumor growth factor (TGF)-β were detected by ELISA...
March 2017: Oncology Letters
https://www.readbyqxmd.com/read/28445515/correlation-of-histopathologic-characteristics-to-protein-expression-and-function-in-malignant-melanoma
#11
Charlotte Welinder, Krzysztof Pawłowski, A Marcell Szasz, Maria Yakovleva, Yutaka Sugihara, Johan Malm, Göran Jönsson, Christian Ingvar, Lotta Lundgren, Bo Baldetorp, Håkan Olsson, Melinda Rezeli, Thomas Laurell, Elisabet Wieslander, György Marko-Varga
BACKGROUND: Metastatic melanoma is still one of the most prevalent skin cancers, which upon progression has neither a prognostic marker nor a specific and lasting treatment. Proteomic analysis is a versatile approach with high throughput data and results that can be used for characterizing tissue samples. However, such analysis is hampered by the complexity of the disease, heterogeneity of patients, tumors, and samples themselves. With the long term aim of quest for better diagnostics biomarkers, as well as predictive and prognostic markers, we focused on relating high resolution proteomics data to careful histopathological evaluation of the tumor samples and patient survival information...
2017: PloS One
https://www.readbyqxmd.com/read/28438383/remitting-seronegative-symmetrical-synovitis-with-pitting-edema-rs3pe-syndrome-induced-by-nivolumab
#12
Marie-Léa Gauci, Barouyr Baroudjian, Pauline Laly, Isabelle Madelaine, Laetitia Da Meda, Laetitia Vercellino, Martine Bagot, Frédéric Lioté, Cécile Pages, Céleste Lebbé
INTRODUCTION: A new articular syndrome described as immunrelated side effect of immunotherapy: PD-1 inhibitors have revolutionized the treatment of advanced melanoma but are responsible for immune-related toxicity. We report a case of remitting seronegative symetrical synovitis with pitting edema (RS3PE) syndrome induced by nivolumab. CASE REPORT: A 80 year-old man with stage IV BRAF-wild type and NRAS exon 2-mutated melanoma was treated first line by nivolumab 3mg/kg every 2 weeks...
March 8, 2017: Seminars in Arthritis and Rheumatism
https://www.readbyqxmd.com/read/28423700/hla-class-i-loss-in-metachronous-metastases-prevents-continuous-t-cell-recognition-of-mutated-neoantigens-in-a-human-melanoma-model
#13
Barbara Schrörs, Silke Lübcke, Volker Lennerz, Martina Fatho, Anne Bicker, Catherine Wölfel, Patrick Derigs, Thomas Hankeln, Dirk Schadendorf, Annette Paschen, Thomas Wölfel
T lymphocytes against tumor-specific mutated neoantigens can induce tumor regression. Also, the size of the immunogenic cancer mutanome is supposed to correlate with the clinical efficacy of checkpoint inhibition. Herein, we studied the susceptibility of tumor cell lines from lymph node metastases occurring in a melanoma patient over several years towards blood-derived, neoantigen-specific CD8+ T cells. In contrast to a cell line established during early stage III disease, all cell lines generated at later time points from stage IV metastases exhibited partial or complete loss of HLA class I expression...
April 25, 2017: Oncotarget
https://www.readbyqxmd.com/read/28401596/successful-retreatment-with-combined-braf-mek-inhibition-in-metastatic-brafv600-mutated-melanoma
#14
Valerie C Amann, Dorothée Hoffmann, Joanna Mangana, Reinhard Dummer, Simone M Goldinger
BACKGROUND: The combination treatment with BRAF- and MEK-inhibitors is amongst the current standard of care for stage IIIC/IV BRAF-mutated melanoma. However, therapeutic options are limited once patients have progressed upon both targeted and immunotherapy. OBJECTIVE: To investigate whether retreatment with BRAF- and MEK-inhibitor combination is an option for patients with metastatic BRAF-mutated melanoma upon previous progression on kinase inhibitors. METHODS: Two patients with metastatic BRAF-mutated melanoma were rechallenged with BRAF- and MEK-inhibitor combination after progression on targeted therapy and subsequent immunotherapy with anti-CTLA-4 and anti-PD-1 antibodies...
April 12, 2017: Journal of the European Academy of Dermatology and Venereology: JEADV
https://www.readbyqxmd.com/read/28397821/t-cell-invigoration-to-tumour-burden-ratio-associated-with-anti-pd-1-response
#15
Alexander C Huang, Michael A Postow, Robert J Orlowski, Rosemarie Mick, Bertram Bengsch, Sasikanth Manne, Wei Xu, Shannon Harmon, Josephine R Giles, Brandon Wenz, Matthew Adamow, Deborah Kuk, Katherine S Panageas, Cristina Carrera, Phillip Wong, Felix Quagliarello, Bradley Wubbenhorst, Kurt D'Andrea, Kristen E Pauken, Ramin S Herati, Ryan P Staupe, Jason M Schenkel, Suzanne McGettigan, Shawn Kothari, Sangeeth M George, Robert H Vonderheide, Ravi K Amaravadi, Giorgos C Karakousis, Lynn M Schuchter, Xiaowei Xu, Katherine L Nathanson, Jedd D Wolchok, Tara C Gangadhar, E John Wherry
Despite the success of monotherapies based on blockade of programmed cell death 1 (PD-1) in human melanoma, most patients do not experience durable clinical benefit. Pre-existing T-cell infiltration and/or the presence of PD-L1 in tumours may be used as indicators of clinical response; however, blood-based profiling to understand the mechanisms of PD-1 blockade has not been widely explored. Here we use immune profiling of peripheral blood from patients with stage IV melanoma before and after treatment with the PD-1-targeting antibody pembrolizumab and identify pharmacodynamic changes in circulating exhausted-phenotype CD8 T cells (Tex cells)...
May 4, 2017: Nature
https://www.readbyqxmd.com/read/28389511/epigenetic-regulation-of-kpc1-ubiquitin-ligase-effects-the-nf-%C3%AE%C2%BAb-pathway-in-melanoma
#16
Yuuki Iida, Aaron Ciechanover, Diego M Marzese, Keisuke Hata, Matias Bustos, Shigeshi Ono, Jinhua Wang, Matthew P Salomon, Kevin Tran, Stella Lam, Sandy C Hsu, Nellie Nelson, Yelena Kravtsova-Ivantsiv, Gordon B Mills, Michael A Davies, Dave Sb Hoon
PURPOSE: Abnormal activation of the NF-κB pathway induces a more aggressive phenotype of cutaneous melanoma. Understanding the mechanisms involved in melanoma NF-κB activation may identify novel targets for this pathway. KPC1, an E3 ubiquitin ligase, is a regulator of NF-κB pathway. The objective of this study was to investigate the mechanisms regulating KPC1 expression and its clinical impact in melanoma. EXPERIMENTAL DESIGN: The clinical impact of KPC1 expression and its epigenetic regulation were assessed in large cohorts of clinically well-annotated melanoma tissues (tissue micro-arrays; n=137, JWCI cohort; n=40) and The Cancer Genome Atlas database (TCGA cohort, n=370)...
April 7, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28359784/ipilimumab-10-mg-kg-versus-ipilimumab-3-mg-kg-in-patients-with-unresectable-or-metastatic-melanoma-a-randomised-double-blind-multicentre-phase-3-trial
#17
Paolo A Ascierto, Michele Del Vecchio, Caroline Robert, Andrzej Mackiewicz, Vanna Chiarion-Sileni, Ana Arance, Céleste Lebbé, Lars Bastholt, Omid Hamid, Piotr Rutkowski, Catriona McNeil, Claus Garbe, Carmen Loquai, Brigitte Dreno, Luc Thomas, Jean-Jacques Grob, Gabriella Liszkay, Marta Nyakas, Ralf Gutzmer, Joanna Pikiel, Florent Grange, Christoph Hoeller, Virginia Ferraresi, Michael Smylie, Dirk Schadendorf, Laurent Mortier, Inge Marie Svane, Delphine Hennicken, Anila Qureshi, Michele Maio
BACKGROUND: A phase 2 trial suggested increased overall survival and increased incidence of treatment-related grade 3-4 adverse events with ipilimumab 10 mg/kg compared with ipilimumab 3 mg/kg in patients with advanced melanoma. We report a phase 3 trial comparing the benefit-risk profile of ipilimumab 10 mg/kg versus 3 mg/kg. METHODS: This randomised, double-blind, multicentre, phase 3 trial was done in 87 centres in 21 countries worldwide. Patients with untreated or previously treated unresectable stage III or IV melanoma, without previous treatment with BRAF inhibitors or immune checkpoint inhibitors, were randomly assigned (1:1) with an interactive voice response system by the permuted block method using block size 4 to ipilimumab 10 mg/kg or 3 mg/kg, administered by intravenous infusion for 90 min every 3 weeks for four doses...
May 2017: Lancet Oncology
https://www.readbyqxmd.com/read/28356222/neutrophil-to-lymphocyte-ratio-is-associated-with-outcome-during-ipilimumab-treatment
#18
Michael R Cassidy, Rachel E Wolchok, Junting Zheng, Katherine S Panageas, Jedd D Wolchok, Daniel Coit, Michael A Postow, Charlotte Ariyan
BACKGROUND: Ipilimumab (IPI) and BRAF inhibitors (BRAFi) improve survival in melanoma, but not all patients will benefit and toxicity can be significant. Pretreatment neutrophil to lymphocyte ratio (NLR) has been associated with outcome in IPI-treated patients, but has not been studied during treatment or in BRAFi-treated patients. METHODS: Using a prospectively maintained database, patients with unresectable stage III or IV melanoma treated with IPI or a BRAFi (vemurafenib or dabrafenib as monotherapy) from 2006 to 2011 were identified...
April 2017: EBioMedicine
https://www.readbyqxmd.com/read/28342215/efficacy-and-safety-of-nivolumab-in-japanese-patients-with-previously-untreated-advanced-melanoma-a-phase-ii-study
#19
Naoya Yamazaki, Yoshio Kiyohara, Hisashi Uhara, Jiro Uehara, Manabu Fujimoto, Tatsuya Takenouchi, Masaki Otsuka, Hiroshi Uchi, Hironobu Ihn, Hironobu Minami
Treating advanced or recurrent melanoma remains a challenge. Cancer cells can evade the immune system by blocking T-cell activation via overexpression of the inhibitory receptor programmed death 1 (PD-1) ligands. The PD-1 inhibitor nivolumab blocks the inhibitory signal in T cells, thus overcoming the immune resistance of cancer cells. Nivolumab has demonstrated promising anti-cancer activity in various cancers. We conducted a single-arm, open-label, multicenter, phase II study to investigate the efficacy and safety of nivolumab in previously untreated Japanese patients with advanced melanoma...
March 25, 2017: Cancer Science
https://www.readbyqxmd.com/read/28334439/a-phase-2-trial-of-dasatinib-in-patients-with-locally-advanced-or-stage-iv-mucosal-acral-or-vulvovaginal-melanoma-a-trial-of-the-ecog-acrin-cancer-research-group-e2607
#20
Kevin Kalinsky, Sandra Lee, Krista M Rubin, Donald P Lawrence, Anthony J Iafrarte, Darell R Borger, Kim A Margolin, Mario M Leitao, Ahmad A Tarhini, Henry B Koon, Andrew L Pecora, Anthony J Jaslowski, Gary I Cohen, Timothy M Kuzel, Christopher D Lao, John M Kirkwood
BACKGROUND: KIT-directed tyrosine kinase inhibitors such as imatinib have demonstrated benefits in KIT-mutant (KIT+) mucosal, acral, vulvovaginal, and chronically sun-damaged (CSD) melanoma. Dasatinib has superior preclinical activity in comparison with other tyrosine kinase inhibitors against cells with the most common KIT mutation, exon 11(L576P) . The ECOG-ACRIN E2607 trial assessed dasatinib in patients with these melanoma subtypes. METHODS: Patients received 70 mg of oral dasatinib twice daily...
March 23, 2017: Cancer
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