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Journal for Immunotherapy of Cancer

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https://www.readbyqxmd.com/read/29463302/the-impact-of-pd-l1-on-survival-and-value-of-the-immune-check-point-inhibitors-in-non-small-cell-lung-cancer-proposal-policies-and-perspective
#1
Helmy M Guirgis
BACKGROUND: The impact of programmed death receptor-ligand1 (PD-L1) on costs and value of the immune check point inhibitors (ICPI) has received minimal attention. OBJECTIVES: 1- Design a sliding scale to grade survival in 2nd-line non-small-cell lung cancer (NSCLC). 2- Compare costs and value of Nivolumab (Nivo), Atezolizumab (Atezo) and Pembrolizumab (Pembro) vs. Docetaxel (Doc). METHODS: Previously reported median overall survival (OS) and prices posted by parent company were utilized...
February 20, 2018: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/29433584/ipilimumab-induced-digital-vasculitis
#2
Amrita Padda, Elena Schiopu, Justin Sovich, Vincent Ma, Ajjai Alva, Leslie Fecher
BACKGROUND: Immune check point inhibitors (ICIs) have emerged as a new therapeutic paradigm for a variety of malignancies including metastatic melanoma. As the use of ICIs expand, immune-mediated adverse events are becoming a common occurrence. CASE PRESENTATION: We describe the first reported patient with small vessel vasculitis, manifested by digital ischemia, following treatment with high dose Ipilimumab for resected stage IIIB/C melanoma. This patient received high dose steroids, five-day intravenous (IV) Epoprostenol protocol, botulinum toxin injections, and Rituximab 375 mg/m2 weekly for four cycles...
February 12, 2018: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/29433571/granulomatous-sarcoid-like-lesions-associated-with-checkpoint-inhibitors-a-marker-of-therapy-response-in-a-subset-of-melanoma-patients
#3
Michael T Tetzlaff, Kelly C Nelson, Adi Diab, Gregg A Staerkel, Priyadharsini Nagarajan, Carlos A Torres-Cabala, Beth A Chasen, Jennifer A Wargo, Victor G Prieto, Rodabe N Amaria, Jonathan L Curry
BACKGROUND: Immune checkpoint therapy has dramatically changed the landscape of cancer therapy, providing an efficacious and durable therapeutic option for patients with advanced-stage disease. However, dermatologic toxicities are a well-recognized side effect in patients receiving this therapy. A spectrum of immune related adverse events (irAEs) involving the skin can occur and include immunobullous disorders, lichenoid dermatitis, and vitiligo. Granulomatous/sarcoid-like lesions are now being recognized with the current class of checkpoint inhibitors (CPIs) that involve the dermis, the subcutaneous tissue (panniculitis), and lymph nodes...
February 12, 2018: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/29433557/metastatic-uveal-melanoma-showing-durable-response-to-anti-ctla-4-and-anti-pd-1-combination-therapy-after-experiencing-progression-on-anti-pd-1-therapy-alone
#4
Muhammad Zubair Afzal, Rodwell Mabaera, Keisuke Shirai
BACKGROUND: Uveal melanoma accounts for 85% of the ocular melanomas and has an increased risk of hematogenous spread, most commonly to the liver. After curative intent therapy like surgery and radiation, fifty percent of patients present with distant metastasis. Metastatic uveal melanoma (MUM) does not harbor typically targetable mutations, e.g., BRAF as in cutaneous melanoma. As a result, there is no proven therapy for MUM. Various chemotherapy and immunotherapy regimens have been tried and only partial response (PR) is the best that has been achieved in most of the cases...
February 12, 2018: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/29382395/mathematical-modeling-of-tumor-associated-macrophage-interactions-with-the-cancer-microenvironment
#5
Grace Mahlbacher, Louis T Curtis, John Lowengrub, Hermann B Frieboes
BACKGROUND: Immuno-oncotherapy has emerged as a promising means to target cancer. In particular, therapeutic manipulation of tumor-associated macrophages holds promise due to their various and sometimes opposing roles in tumor progression. It is established that M1-type macrophages suppress tumor progression while M2-types support it. Recently, Tie2-expressing macrophages (TEM) have been identified as a distinct sub-population influencing tumor angiogenesis and vascular remodeling as well as monocyte differentiation...
January 30, 2018: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/29382383/inflammatory-demyelinating-polyneuropathy-versus-leptomeningeal-disease-following-ipilimumab
#6
Lorraine Cafuir, David Lawson, Nilesh Desai, Vita Kesner, Alfredo Voloschin
BACKGROUND: Ipilimumab is an FDA-approved anti-CTLA-4 monoclonal antibody used in treatment of metastatic melanoma. We present an unusual neurological complication of Ipilimumab therapy and the diagnostic dilemma it caused. CASE PRESENTATION: A 42 year old male with Stage IV metastatic melanoma developed lower extremity weakness and sensory neuropathy following three doses of Ipilimumab. MRI of the lumbar spine was initially interpreted as diffuse leptomeningeal disease, and patient began Dexamethasone and radiation with improvement in symptoms...
January 30, 2018: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/29378660/clinical-activity-of-nivolumab-in-patients-with-non-clear-cell-renal-cell-carcinoma
#7
Vadim S Koshkin, Pedro C Barata, Tian Zhang, Daniel J George, Michael B Atkins, William J Kelly, Nicholas J Vogelzang, Sumanta K Pal, JoAnn Hsu, Leonard J Appleman, Moshe C Ornstein, Timothy Gilligan, Petros Grivas, Jorge A Garcia, Brian I Rini
BACKGROUND: Nivolumab is approved for patients with metastatic renal cell carcinoma (mRCC) refractory to prior antiangiogenic therapy. The clinical activity of nivolumab in patients with non-clear cell RCC subtypes remains unknown as these patients were excluded from the original nivolumab trials. METHODS: Patients from 6 centers in the United States who received at least one dose of nivolumab for non-clear cell mRCC between 12/2015 and 06/2017 were identified. A retrospective analysis including patient characteristics, objective response rate according to RECIST v1...
January 29, 2018: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/29375032/incorporating-radiation-oncology-into-immunotherapy-proceedings-from-the-astro-sitc-nci-immunotherapy-workshop
#8
Ariel E Marciscano, Joshua M Walker, Heather M McGee, Michelle M Kim, Charles A Kunos, Arta M Monjazeb, Stephen L Shiao, Phuoc T Tran, Mansoor M Ahmed
Radiotherapy (RT) has been a fundamental component of the anti-cancer armamentarium for over a century. Approximately half of all cancer patients are treated with radiotherapy during their disease course. Over the two past decades, there has been a growing body of preclinical evidence supporting the immunomodulatory effects of radiotherapy, particularly when combined with immunotherapy, but only anecdotal clinical examples existed until recently. The renaissance of immunotherapy and the recent U.S. Food and Drug Administration (FDA) approval of several immune checkpoint inhibitors (ICIs) and other immuno-oncology (IO) agents in multiple cancers provides the opportunity to investigate how localized radiotherapy can induce systemic immune responses...
January 29, 2018: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/29368638/biomarkers-of-immunotherapy-in-urothelial-and-renal-cell-carcinoma-pd-l1-tumor-mutational-burden-and-beyond
#9
REVIEW
Jason Zhu, Andrew J Armstrong, Terence W Friedlander, Won Kim, Sumanta K Pal, Daniel J George, Tian Zhang
Immune checkpoint inhibitors targeting the PD-1 pathway have greatly changed clinical management of metastatic urothelial carcinoma and metastatic renal cell carcinoma. However, response rates are low, and biomarkers are needed to predict for treatment response. Immunohistochemical quantification of PD-L1 was developed as a promising biomarker in early clinical trials, but many shortcomings of the four different assays (different antibodies, disparate cellular populations, and different thresholds of positivity) have limited its clinical utility...
January 25, 2018: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/29357948/development-of-pd-1-and-pd-l1-inhibitors-as-a-form-of-cancer-immunotherapy-a-comprehensive-review-of-registration-trials-and-future-considerations
#10
REVIEW
Jun Gong, Alexander Chehrazi-Raffle, Srikanth Reddi, Ravi Salgia
Early preclinical evidence provided the rationale for programmed cell death 1 (PD-1) and programmed death ligand 1 (PD-L1) blockade as a potential form of cancer immunotherapy given that activation of the PD-1/PD-L1 axis putatively served as a mechanism for tumor evasion of host tumor antigen-specific T-cell immunity. Early-phase studies investigating several humanized monoclonal IgG4 antibodies targeting PD-1 and PD-L1 in advanced solid tumors paved way for the development of the first PD-1 inhibitors, nivolumab and pembrolizumab, approved by the Food and Drug Administration (FDA) in 2014...
January 23, 2018: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/29353553/change-in-neutrophil-to-lymphocyte-ratio-nlr-in-response-to-immune-checkpoint-blockade-for-metastatic-renal-cell-carcinoma
#11
Aly-Khan A Lalani, Wanling Xie, Dylan J Martini, John A Steinharter, Craig K Norton, Katherine M Krajewski, Audrey Duquette, Dominick Bossé, Joaquim Bellmunt, Eliezer M Van Allen, Bradley A McGregor, Chad J Creighton, Lauren C Harshman, Toni K Choueiri
BACKGROUND: An elevated Neutrophil-to-lymphocyte ratio (NLR) is associated with worse outcomes in several malignancies. However, its role with contemporary immune checkpoint blockade (ICB) is unknown. We investigated the utility of NLR in metastatic renal cell carcinoma (mRCC) patients treated with PD-1/PD-L1 ICB. METHODS: We examined NLR at baseline and 6 (±2) weeks later in 142 patients treated between 2009 and 2017 at Dana-Farber Cancer Institute (Boston, USA)...
January 22, 2018: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/29347993/updated-efficacy-of-avelumab-in-patients-with-previously-treated-metastatic-merkel-cell-carcinoma-after-%C3%A2-1-year-of-follow-up-javelin-merkel-200-a-phase-2-clinical-trial
#12
Howard L Kaufman, Jeffery S Russell, Omid Hamid, Shailender Bhatia, Patrick Terheyden, Sandra P D'Angelo, Kent C Shih, Céleste Lebbé, Michele Milella, Isaac Brownell, Karl D Lewis, Jochen H Lorch, Anja von Heydebreck, Meliessa Hennessy, Paul Nghiem
BACKGROUND: Merkel cell carcinoma (MCC) is a rare, aggressive skin cancer associated with poor survival outcomes in patients with distant metastatic disease (mMCC). In an initial analysis from JAVELIN Merkel 200, a phase 2, prospective, open-label, single-arm trial in mMCC, avelumab-a human anti-programmed death-ligand 1 (PD-L1) monoclonal antibody-showed promising efficacy and a safety profile that was generally manageable and tolerable. Here, we report the efficacy of avelumab after ≥1 year of follow-up in patients with distant mMCC that had progressed following prior chemotherapy for metastatic disease...
January 19, 2018: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/29332608/concealed-complete-response-in-melanoma-patients-under-therapy-with-immune-checkpoint-inhibitors-two-case-reports
#13
Stefan Schliep, Abbas Agaimy, Alexander Cavallaro, Franklin Kiesewetter, Gerold Schuler, Lucie Heinzerling
BACKGROUND: The assessment of tumor size by RECIST using CT scans and MRIs is considered to be standard of care for staging cancer patients. Despite radiologic evidence of widespread disease, we document for the first time that patients were completely free of viable tumor. CASE PRESENTATION: Two patients with metastatic melanoma were treated with immune checkpoint inhibitors (ipilimumab/ nivolumab) and progressive metastases were detected on CT-scans performed shortly before histologic examinations...
January 15, 2018: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/29307306/viruses-bacteria-and-parasites-oh-my-a-resurgence-of-interest-in-microbial-based-therapy-for-cancer
#14
EDITORIAL
Andrew Zloza
As infections and cancer are two of the most common maladies affecting human beings, a concerted effort is needed to better understand their potential interactions and to further explore their use in microbial-based cancer treatments. Studies focusing on the interaction between pathogens and cancer began over 4000 years ago, but therapeutic application of pathogens has often been bypassed as other cancer therapies have gained wider interest. To many, the field of microbial-based cancer treatment may feel antiquated and already sufficiently explored...
January 8, 2018: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/29298730/cytokine-release-syndrome-after-radiation-therapy-case-report-and-review-of-the-literature
#15
Christopher A Barker, Samuel K Kim, Sadna Budhu, Konstantina Matsoukas, Anthony F Daniyan, Sandra P D'Angelo
BACKGROUND: Cytokine release syndrome (CRS) has been reported after immunologic manipulations, most often through therapeutic monoclonal antibodies. To our knowledge, CRS after radiation therapy (RT) for cancer has not been reported before. The development of unusual clinical signs and symptoms after RT led us to investigate the possibility of CRS after RT and review the medical literature on this topic. CASE PRESENTATION: A 65 year-old man with untreated chronic lymphocytic leukemia and recurrent, metastatic Merkel cell carcinoma undergoing anti-programmed death 1 (PD1) immunotherapy was referred for palliative RT to sites of progressing metastases...
January 3, 2018: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/29258618/a-pilot-study-of-an-autologous-tumor-derived-autophagosome-vaccine-with-docetaxel-in-patients-with-stage-iv-non-small-cell-lung-cancer
#16
Rachel E Sanborn, Helen J Ross, Sandra Aung, Anupama Acheson, Tarsem Moudgil, Sachin Puri, Traci Hilton, Brenda Fisher, Todd Coffey, Christopher Paustian, Michael Neuberger, Edwin Walker, Hong-Ming Hu, Walter J Urba, Bernard A Fox
BACKGROUND: Tumor-derived autophagosome vaccines (DRibbles) have the potential to broaden immune response to poorly immunogenic tumors. METHODS: Autologous vaccine generated from tumor cells harvested from pleural effusions was administered to patients with advanced NSCLC with the objectives of assessing safety and immune response. Four patients were vaccinated and evaluable for immune response; each received two to four doses of vaccine. Study therapy included two cycles of docetaxel 75 mg/m2 on days 1 and 29 to treat the tumor, release hidden antigens and produce lymphopenia...
December 19, 2017: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/29254508/inhibition-of-arginase-by-cb-1158-blocks-myeloid-cell-mediated-immune-suppression-in-the-tumor-microenvironment
#17
Susanne M Steggerda, Mark K Bennett, Jason Chen, Ethan Emberley, Tony Huang, Julie R Janes, Weiqun Li, Andrew L MacKinnon, Amani Makkouk, Gisele Marguier, Peter J Murray, Silinda Neou, Alison Pan, Francesco Parlati, Mirna L M Rodriguez, Lee-Ann Van de Velde, Tracy Wang, Melissa Works, Jing Zhang, Winter Zhang, Matthew I Gross
BACKGROUND: Myeloid cells are an abundant leukocyte in many types of tumors and contribute to immune evasion. Expression of the enzyme arginase 1 (Arg1) is a defining feature of immunosuppressive myeloid cells and leads to depletion of L-arginine, a nutrient required for T cell and natural killer (NK) cell proliferation. Here we use CB-1158, a potent and orally-bioavailable small-molecule inhibitor of arginase, to investigate the role of Arg1 in regulating anti-tumor immunity. METHODS: CB-1158 was tested for the ability to block myeloid cell-mediated inhibition of T cell proliferation in vitro, and for tumor growth inhibition in syngeneic mouse models of cancer as a single agent and in combination with other therapies...
December 19, 2017: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/29254507/radiotherapy-enhances-natural-killer-cell-cytotoxicity-and-localization-in-pre-clinical-canine-sarcomas-and-first-in-dog-clinical-trial
#18
Robert J Canter, Steven K Grossenbacher, Jennifer A Foltz, Ian R Sturgill, Jiwon S Park, Jesus I Luna, Michael S Kent, William T N Culp, Mingyi Chen, Jaime F Modiano, Arta M Monjazeb, Dean A Lee, William J Murphy
BACKGROUND: We have previously shown that radiotherapy (RT) augments natural killer (NK) functions in pre-clinical models of human and mouse cancers, including sarcomas. Since dogs are an excellent outbred model for immunotherapy studies, we sought to assess RT plus local autologous NK transfer in canine sarcomas. METHODS: Dog NK cells (CD5dim, NKp46+) were isolated from PBMCs and expanded with irradiated K562-C9-mIL21 feeder cells and 100 IU/mL recombinant human IL-2...
December 19, 2017: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/29254506/improved-survival-and-tumor-control-with-interleukin-2-is%C3%A2-associated-with-the-development-of-immune-related-adverse-events-data-from-the-proclaimsm-registry
#19
Brendan Curti, Gregory A Daniels, David F McDermott, Joseph I Clark, Howard L Kaufman, Theodore F Logan, Jatinder Singh, Meenu Kaur, Theresa L Luna, Nancy Gregory, Michael A Morse, Michael K K Wong, Janice P Dutcher
BACKGROUND: Immune related adverse events (irAEs) are associated with immunotherapy for cancer and while results suggest improvement in tumor control and overall survival in those experiencing irAEs, the long-term impact is debated. We evaluated irAE reports related to high dose interleukin-2 therapy (IL-2) documented in the PROCLAIMSM registry data base from 2008 to 2016 (NCT01415167, August 9, 2011). METHODS: Reports on 1535 patients, including 623 with metastatic melanoma (mM) and 919 with metastatic renal cell cancer (mRCC) (7 patients had both diseases), were queried for irAEs...
December 19, 2017: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/29254505/anti-pd-1-vasculitis-of-the-central-nervous-system-or-radionecrosis
#20
EDITORIAL
Roger Sun, Francois-Xavier Danlos, Samy Ammari, Guillaume Louvel, Frédéric Dhermain, Stéphane Champiat, Olivier Lambotte, Eric Deutsch
Commentary on « Cerebral vasculitis mimicking intracranial metastatic progression of lung cancer during PD-1 blockade » by Läubli H et al., J Immunother Cancer. 2017;5:46.The authors diagnosed a cerebral tumor-like lymphocytic vasculitis associated with anti-endothelial cell auto-antibodies secondary to anti-PD-1 therapy, treated by surgical resection and corticosteroids. We thought that this diagnosis should be discussed for at least two reasons. First, etiological explorations were not sufficient. Second, the diagnostic of radionecrosis should also be discussed...
December 19, 2017: Journal for Immunotherapy of Cancer
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