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https://www.readbyqxmd.com/read/28088309/-new-therapy-outlooks-in-hodgkin-lymphoma
#1
REVIEW
Cédric Rossi, René-Olivier Casasnovas
Classical Hodgkin lymphoma (HL) is a curable disease in 80% of advanced and 90% of localized stages. An improvement of the HL curability is still possible with the emergence of first-line therapy with a better balance between efficacy and toxicity and early identification patients with high risk of failure requiring specific treatment. 18FDG PET-CT gained a major role in the baseline staging and response assessment to HL treatment. The prognostic value of early PET-CT allowed to develop PET-CT guided therapies able to optimize the balance between efficacy and toxicity including the modulation of the chemotherapy intensity or the omission of radiotherapy for some localized diseases...
January 11, 2017: Bulletin du Cancer
https://www.readbyqxmd.com/read/28073132/hypothyroidism-in-cancer-patients-on-immune-checkpoint-inhibitors-with-anti-pd1-agents-insights-on-underlying-mechanisms
#2
M Alhusseini, J Samantray
Background: Immune therapy using monoclonal antibodies against cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) and programmed cell death 1 receptor (PD-1) for various cancers have been reported to cause thyroid dysfunction. Little is known, however, about the underlying pathogenic mechanisms and the course of hypothyroidism that subsequently develops. In this report, we use the change in thyroglobulin and thyroid antibody levels in patients on immune therapy who develop hypothyroidism to better understand its pathogenesis as well as examine the status of hypothyroidism in the long term...
January 10, 2017: Experimental and Clinical Endocrinology & Diabetes
https://www.readbyqxmd.com/read/28064139/neurological-adverse-events-associated-with-immune-checkpoint-inhibitors-review-of-the-literature
#3
REVIEW
S Cuzzubbo, F Javeri, M Tissier, A Roumi, C Barlog, J Doridam, C Lebbe, C Belin, R Ursu, A F Carpentier
Immune checkpoint inhibitors (ICIs) targeting CTLA4 and PD1 constitute a promising class of cancer treatment but are associated with several immune-related disorders. We here review the literature reporting neurological adverse events (nAEs) associated with ICIs. A systematic search of literature, up to February 2016, mentioning nAEs in patients treated with ICIs was conducted. Eligible studies included case reports and prospective trials. One case seen in our ward was also added. Within the 59 clinical trials (totalling 9208 patients) analysed, the overall incidence of nAEs was 3...
January 5, 2017: European Journal of Cancer
https://www.readbyqxmd.com/read/28055269/targeting-pd-1-pathway-a-new-hope-for-gastrointestinal-cancers
#4
Burak Bilgin, Mehmet An Sendur, Muhammed Bülent Akıncı, Didem Şener Dede, Bülent Yalçın
BACKGROUND: VEGF, HER2 and EGFR targeted agents are currently used in gastric, esophageal and colorectal cancers. However, treatment outcomes are still poor in most of the Gastrointestinal (GI) cancers. Immune checkpoints are one of the most promising immunotherapy approaches. In this review article, we aimed to discuss the efficacy and safety of anti-PD-1/PD-L1 therapies in GI cancers, including gastric, esophageal and colorectal cancer in the era of published or reported recent studies...
January 5, 2017: Current Medical Research and Opinion
https://www.readbyqxmd.com/read/28031159/evolution-of-neoantigen-landscape-during-immune-checkpoint-blockade-in-non-small-cell-lung-cancer
#5
Valsamo Anagnostou, Kellie N Smith, Patrick M Forde, Noushin Niknafs, Rohit Bhattacharya, James White, Theresa Zhang, Vilmos Adleff, Jillian Phallen, Neha Wali, Carolyn Hruban, Violeta B Guthrie, Kristen Rodgers, Jarushka Naidoo, Hyunseok Kang, William H Sharfman, Christos Georgiades, Franco Verde, Peter Illei, Qing Kay Li, Edward Gabrielson, Malcolm V Brock, Cynthia A Zahnow, Stephen B Baylin, Robert Scharpf, Julie R Brahmer, Rachel Karchin, Drew M Pardoll, Victor E Velculescu
Immune checkpoint inhibitors have shown significant therapeutic responses against tumors containing increased mutation-associated neoantigen load. We have examined the evolving landscape of tumor neoantigens during the emergence of acquired resistance in non-small cell lung cancer patients after initial response to immune checkpoint blockade with anti-PD1 or anti-PD-1/anti-CTLA4 antibodies. Analyses of matched pretreatment and resistant tumors identified genomic changes resulting in loss of 7 to 18 putative mutation-associated neoantigens in resistant clones...
December 28, 2016: Cancer Discovery
https://www.readbyqxmd.com/read/28007774/combined-kit-and-ctla-4-blockade-in-patients-with-refractory-gist-and-other-advanced-sarcomas-a-phase-ib-study-of-dasatinib-plus-ipilimumab
#6
Sandra P D'Angelo, Alexander N Shoushtari, Mary Louise Keohan, Mark A Dickson, Mrinal M Gounder, Ping Chi, Jennifer K Loo, Leigh Gaffney, Lee Schneider, Zarine Patel, Joseph P Erinjeri, Mark Bluth, Ana Sjoberg, Howard Streicher, Naoko Takebe, Li-Xuan Qin, Cristina R Antonescu, Ronald P DeMatteo, Richard D Carvajal, William D Tap
PURPOSE: A phase Ib study of dasatinib plus ipilimumab in GIST and other sarcomas was performed based on pre-clinical data demonstrating that combined KIT and CTLA-4 blockade is synergistic. EXPERIMENTAL DESIGN: A standard 3+3 design was used evaluate the safety, efficacy and immune correlates of treatment. Dose escalation cohorts received ipilimumab 10 or 3 mg/kg every 3 weeks followed by maintenance every 12 weeks with escalating doses of dasatinib (70mg daily, 100 mg daily or 70 mg twice daily)...
December 22, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28003307/pi3k-inhibition-reduces-mammary-tumor-growth-and-facilitates-anti-tumor-immunity-and-anti-pd1-responses
#7
Jiqing Sai, Philip Owens, Sergey V Novitiskiy, Oriana E Hawkins, Anna E Vilgelm, Jinming Yang, Tammy Sobolik-Delmaire, Nicole Lavender, Andrew C Johnson, Colt McClain, Gregory D Ayers, Mark C Kelley, Melinda Sanders, Ingrid A Mayer, Harold L Moses, Mark Boothby, Ann Richmond
PURPOSE: Metastatic breast cancers continue to elude current therapeutic strategies, including those utilizing PI3K inhibitors. Given the prominent role of PI3Kα,β in tumor growth and PI3Kγ,δ in immune cell function, we sought to determine whether PI3K inhibition altered anti-tumor immunity. EXPERIMENTAL DESIGN: The effect of PI3K inhibition on tumor growth, metastasis, and anti-tumor immune response was characterized in mouse models utilizing orthotopic implants of 4T1 or PyMT mammary tumors into syngeneic or PI3Kγ null mice, and patient-derived breast cancer xenografts in humanized mice...
December 21, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28003304/genomic-profiling-of-patient-derived-xenografts-for-lung-cancer-identifies-b2m-inactivation-impairing-immunorecognition
#8
Carolina Pereira, Pol Gimenez-Xavier, Eva Pros, Maria J Pajares, Massimo Moro, Antonio Gomez, Alejandro Navarro, Enric Condom, Sebastian Moran, Gonzalo Gómez-López, Osvaldo Graña, Miriam Rubio-Camarillo, Alex Martinez-Martí, Jun Yokota, Julian Carretero, Jose M Galbis, Ernest Nadal, David G Pisano, Gabriella Sozzi, Enriqueta Felip, Luis M Montuenga, Luca Roz, Alberto Villanueva, Montse Sanchez-Cespedes
PURPOSE: We aimed to maximize the performance of detecting genetic alterations in lung cancer (LC) using high-throughput sequencing for patient-derived xenografts (PDXs). EXPERIMENTAL DESIGN: We undertook an integrated RNA and whole-exome sequencing of 14 PDXs. We focused on the genetic and functional analysis of B2-microglobulin (B2M), a component of the HLA class-I complex. RESULTS: We identified alterations in genes involved in various functions, such as B2M involved in immunosurveillance...
December 21, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28000240/epidermal-anti-programmed-cell-death-ligand-1-expression-in-ten-associated-with-nivolumab-therapy
#9
Karina L Vivar, Maria Deschaine, Jane Messina, Jennifer M Divine, Alejandro Rabionet, Nishit Patel, Michael A Harrington, Lucia Seminario-Vidal
BACKGROUND: Nivolumab is an anti-programmed cell death receptor-1 (PD-1) antibody used in the treatment of metastatic or unresectable melanoma. Cutaneous reactions are the most common adverse events reported with these agents and are rarely severe or life-threatening. METHODS: Case report describing the clinicopathological findings of a patient with a fatal toxic epidermal necrolysis (TEN) eruption associated with use of nivolumab for treatment of metastatic melanoma...
December 21, 2016: Journal of Cutaneous Pathology
https://www.readbyqxmd.com/read/27997006/-nivolumab-in-second-line-treatment-of-squamous-non-small-cell-lung-cancer
#10
Filippo De Marinis, Antonio Passaro
The treatment of non-small cell lung cancer (NSCLC) is changing dramatically in the last period, considering both non-squamous and squamous disease. In the last five years, the identification of different molecular predictive biomarker (e.g., EGFR, ALK e ROS1) and the utilize of new chemotherapy agents associated or not with antiangiogenics agents (e.g., bevacizumab and nintedanib), allowed the improvement of survival and related responses to these treatments. However, these advances, did not allow an improvement of the same endpoints in the management of NSCLC with squamous cell histology (SCC), where until very recently, docetaxel in monotherapy remained as a corner stone treatment for the second line, although associated with an unfavorable toxicity profile...
December 2016: Recenti Progressi in Medicina
https://www.readbyqxmd.com/read/27969531/ps01-64-effect-of-anti-pd1-therapy-on-the-incidence-of-thromboembolic-events-in%C3%A2-lung-cancer-topic-medical-oncology
#11
Aparna Hegde, Cindy Cherry, Geoff Stroud, Sulochana Cherukuri, Paul R Walker
No abstract text is available yet for this article.
November 2016: Journal of Thoracic Oncology
https://www.readbyqxmd.com/read/27969473/ps01-05-early-and-persistent-oligoclonal-t-cell-expansion-correlates-with-durable-response-to-anti-pd1-therapy-in-nsclc-topic-medical-oncology
#12
Sope Olugbile, Kazuma Kiyotani, Jae-Hyun Park, Philip Hoffman, Livia Szeto, Jyoti Patel, Everett Vokes, Yusuke Nakamura
No abstract text is available yet for this article.
November 2016: Journal of Thoracic Oncology
https://www.readbyqxmd.com/read/27951441/resistance-to-pd1-pdl1-checkpoint-inhibition
#13
REVIEW
Jake S O'Donnell, Georgina V Long, Richard A Scolyer, Michele W L Teng, Mark J Smyth
For the first time in decades, patients with difficult-to-treat cancers such as advanced stage metastatic melanoma are being offered a glimpse of hope in the form of immunotherapies. By targeting factors that foster the development and maintenance of an immunosuppressive microenvironment within tumors, these therapies release the brakes on the host's own immune system; allowing cure of disease. Indeed, phase III clinical trials have revealed that therapies such as ipilimumab and pembrolizumab which target the CTLA4 and PD-1 immune checkpoints, respectively, have raised the three-year survival of patients with melanoma to ∼70%, and overall survival (>5years) to ∼30%...
January 2017: Cancer Treatment Reviews
https://www.readbyqxmd.com/read/27942391/metastatic-basal-cell-carcinoma-with-amplification-of-pd-l1-exceptional-response-to-anti-pd1-therapy
#14
Sadakatsu Ikeda, Aaron M Goodman, Philip R Cohen, Taylor J Jensen, Christopher K Ellison, Garrett Frampton, Vincent Miller, Sandip P Patel, Razelle Kurzrock
Metastatic basal cell carcinomas are rare malignancies harbouring Hedgehog pathway alterations targetable by SMO antagonists (vismodegib/sonidegib). We describe, for the first time, the molecular genetics and response of a patient with Hedgehog inhibitor-resistant metastatic basal cell carcinoma who achieved rapid tumour regression (ongoing near complete remission at 4 months) with nivolumab (anti-PD1 antibody). He had multiple hallmarks of anti-PD1 responsiveness including high mutational burden (> 50 mutations per megabase; 19 functional alterations in tissue next-generation sequencing (NGS; 315 genes)) as well as PDL1/PDL2/JAK2 amplification (as determined by both tissue NGS and by analysis of plasma-derived cell-free DNA)...
2016: NPJ Genomic Medicine
https://www.readbyqxmd.com/read/27940380/biomimetic-biodegradable-artificial-antigen-presenting-cells-synergize-with-pd-1-blockade-to-treat-melanoma
#15
A K Kosmides, R A Meyer, J W Hickey, K Aje, K N Cheung, J J Green, J P Schneck
Biomimetic materials that target the immune system and generate an anti-tumor responses hold promise in augmenting cancer immunotherapy. These synthetic materials can be engineered and optimized for their biodegradability, physical parameters such as shape and size, and controlled release of immune-modulators. As these new platforms enter the playing field, it is imperative to understand their interaction with existing immunotherapies since single-targeted approaches have limited efficacy. Here, we investigate the synergy between a PLGA-based artificial antigen presenting cell (aAPC) and a checkpoint blockade molecule, anti-PD1 monoclonal antibody (mAb)...
February 2017: Biomaterials
https://www.readbyqxmd.com/read/27926587/anti-programmed-cell-death-protein-1-tolerance-and-efficacy-after-ipilimumab-immunotherapy-observational-study-of-39-patients
#16
Reyhan Amode, Barouyr Baroudjian, Anita Kowal, Majdi Jebali, Clara Allayous, Martine Bagot, Nika Madjlessi, Jennifer Roux, Manuelle Viguier, Nicole Basset Seguin, Raphaël Porcher, Cécile Pagès, Céleste Lebbé
In patients with ipilimumab (IPI)-refractory melanoma, the anti-programmed cell death proteins 1 (PD1s) nivolumab (NIV) and pembrolizumab (PEM) are considered to be a new standard of treatment. Few data are available on anti-PD1 safety in patients who develop IPI-related severe adverse events (AEs) (grade≥3). The aim of this study was to compare the anti-PD1 safety and efficacy in patients with previous severe toxicity to IPI versus in those showing moderate and no previous IPI-related AEs. This single institution-based observational study included all patients treated with anti-PD1 (PEM or NIV) and previously treated with IPI for unresectable stage III or IV melanoma...
December 6, 2016: Melanoma Research
https://www.readbyqxmd.com/read/27912061/tumor-interferon-signaling-regulates-a-multigenic-resistance-program-to-immune-checkpoint-blockade
#17
Joseph L Benci, Bihui Xu, Yu Qiu, Tony J Wu, Hannah Dada, Christina Twyman-Saint Victor, Lisa Cucolo, David S M Lee, Kristen E Pauken, Alexander C Huang, Tara C Gangadhar, Ravi K Amaravadi, Lynn M Schuchter, Michael D Feldman, Hemant Ishwaran, Robert H Vonderheide, Amit Maity, E John Wherry, Andy J Minn
Therapeutic blocking of the PD1 pathway results in significant tumor responses, but resistance is common. We demonstrate that prolonged interferon signaling orchestrates PDL1-dependent and PDL1-independent resistance to immune checkpoint blockade (ICB) and to combinations such as radiation plus anti-CTLA4. Persistent type II interferon signaling allows tumors to acquire STAT1-related epigenomic changes and augments expression of interferon-stimulated genes and ligands for multiple T cell inhibitory receptors...
December 1, 2016: Cell
https://www.readbyqxmd.com/read/27911126/anti-pd1-treatment-in-metastatic-uveal-melanoma-in-the-netherlands
#18
M K van der Kooij, A Joosse, F M Speetjens, G A P Hospers, C Bisschop, J W B de Groot, R Koornstra, C U Blank, E Kapiteijn
No abstract text is available yet for this article.
January 2017: Acta Oncologica
https://www.readbyqxmd.com/read/27895920/pd1-pd-l1-inhibition-as-a-potential-radiosensitizer-in-head-and-neck-squamous-cell-carcinoma-a-case-report
#19
Misako Nagasaka, Mark Zaki, Harold Kim, S Naweed Raza, George Yoo, Ho-Sheng Lin, Ammar Sukari
BACKGROUND: Immunotherapy targeting the checkpoint PD1 (programmed cell death protein 1) or PDL1 (programmed death ligand 1) has led to advances in the treatment of melanoma and non-small cell lung cancer (NSCLC). The use of such therapies has also been introduced into the treatment of other malignancies, including head and neck cancer. The combined effects of checkpoint inhibitors and anti-PD1(L1) antibodies and radiation therapy have not yet been sufficiently investigated. CASE PRESENTATION: We report a case of locally relapsed non-resectable oral cavity squamous cell carcinoma, with excellent local control after pembrolizumab (MK3475) followed by radiotherapy...
2016: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/27885401/-cutaneous-side-effects-of-targeted-cancer-drugs
#20
REVIEW
J Below, B Homey, P A Gerber
In the past decades many new drugs were approved for the treatment of cancer and have been established as essential parts of various therapeutic regimens. In particular targeted therapies and immune checkpoint inhibitors that aim at specific carcinogenic signaling pathways or modulate the tumor-immune response have revolutionized cancer therapy. Despite their targeted actions, these drugs may lead to diverse adverse reactions. In particular, cutaneous toxicities represent a serious threat to patients' quality of life and may lead to dose reduction or therapy cessation...
November 24, 2016: Der Hautarzt; Zeitschrift Für Dermatologie, Venerologie, und Verwandte Gebiete
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