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Journal for Immunotherapy of Cancer

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https://www.readbyqxmd.com/read/29622046/complete-intracranial-response-to-talimogene-laherparepvec-t-vec-pembrolizumab-and-whole-brain-radiotherapy-in-a-patient-with-melanoma-brain-metastases-refractory-to-dual-checkpoint-inhibition
#1
Zoë Blake, Douglas K Marks, Robyn D Gartrell, Thomas Hart, Patti Horton, Simon K Cheng, Bret Taback, Basil A Horst, Yvonne M Saenger
BACKGROUND: Immunotherapy, in particular checkpoint blockade, has changed the clinical landscape of metastatic melanoma. Nonetheless, the majority of patients will either be primary refractory or progress over follow up. Management of patients progressing on first-line immunotherapy remains challenging. Expanded treatment options with combination immunotherapy has demonstrated efficacy in patients previously unresponsive to single agent or alternative combination therapy. CASE PRESENTATION: We describe the case of a patient with diffusely metastatic melanoma, including brain metastases, who, despite being treated with stereotactic radiosurgery and dual CTLA-4/PD-1 blockade (ipilimumab/nivolumab), developed systemic disease progression and innumerable brain metastases...
April 6, 2018: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/29618380/coordinated-responses-to-individual-tumor-antigens-by-igg-antibody-and-cd8-t-cells-following-cancer-vaccination
#2
Tyler W Hulett, Shawn M Jensen, Phillip A Wilmarth, Ashok P Reddy, Carmen Ballesteros-Merino, Michael E Afentoulis, Christopher Dubay, Larry L David, Bernard A Fox
BACKGROUND: One of today's greatest hurdles for cancer immunotherapy is the absence of information regarding which tumor antigens are already recognized by patients receiving immunotherapies, and whether those therapies then boost or generate an immune response against tumor proteins. For CD8+ T cells in particular, patient-specific immune recognition and responses at the level of individual tumor antigens are rarely characterized. Because of this, some immunologists have turned to serum antibodies as an alternative measure of antigen-specific anti-tumor immunity...
April 5, 2018: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/29618381/efficacy-of-pd-1-pd-l1-inhibitors-in-older-adults-a-meta-analysis
#3
Rawad Elias, Anita Giobbie-Hurder, Nadine Jackson McCleary, Patrick Ott, F Stephen Hodi, Osama Rahma
BACKGROUND: Immune checkpoint inhibitors targeting PD-1/PD-L1 pathway demonstrated promising activities in variety of malignancies, however little is known regarding their efficacy in adults aged ≥65 years. METHODS: We conducted a systematic review and a study-level meta-analysis to explore efficacy of ICIs based on age, younger vs older than 65 years. We included in this analysis randomized controlled phase II or III studies in patients with metastatic solid tumors that compared efficacy of PD-1 or PD-L1 inhibitors to a non-PD-1/PD-L1 inhibitor...
April 4, 2018: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/29618376/pseudoprogression-manifesting-as-recurrent-ascites-with-anti-pd-1-immunotherapy-in-urothelial-bladder-cancer
#4
Randy F Sweis, Yuanyuan Zha, Lomax Pass, Brian Heiss, Tara Chongsuwat, Jason J Luke, Thomas F Gajewski, Russell Szmulewitz
BACKGROUND: Immunotherapies targeting the PD-1 checkpoint pathway have recently gained regulatory approval in numerous cancer types. With the widespread use of immune checkpoint therapies, varying patterns of responses and immune-related adverse events are being observed. CASE PRESENTATION: In this case, we highlight a patient who developed recurrent, large-volume ascites, while simultaneously having a 49% reduction in peritoneal tumor lesion size by RECIST criteria...
April 4, 2018: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/29566749/immunotherapy-for-merkel-cell-carcinoma-a-turning-point-in-patient-care
#5
Isaac S Chan, Shailender Bhatia, Howard L Kaufman, Evan J Lipson
Merkel Cell carcinoma (MCC) is a rare but aggressive cancer, with an estimated disease-associated mortality as high as 46%. MCC has proven to be an immunologically responsive disease and the advent of immune checkpoint inhibitors has changed the treatment landscape for patients with advanced MCC. In this review, we discuss the rationale for the use of immune checkpoint inhibition, review current single agent therapies tested in and approved for MCC, and discuss emerging immunotherapeutic options for these patients...
March 23, 2018: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/29548299/severe-immune-mucositis-and-esophagitis-in-metastatic-squamous-carcinoma-of-the-larynx-associated-with-pembrolizumab
#6
Fanny Zulay Acero Brand, Nicolas Suter, Jean-Philippe Adam, Bernard Faulques, Antonio Maietta, Denis Soulières, Normand Blais
BACKGROUND: Pembrolizumab is an anti-programmed death 1 (PD-1) receptor monoclonal antibody that has shown activity as second line treatment for metastatic head and neck squamous cell carcinoma (HNSCC). Immune-related adverse events are now well described complications of PD-1 inhibitors and most organ sites have been shown to be potentially affected. CASE PRESENTATION: We describe a 69-year old patient with a relapsed squamous cell carcinoma of the supraglottic larynx with lung metastasis after receiving adjuvant concurrent cisplatin and radiotherapy...
March 16, 2018: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/29534736/prime-boost-vaccination-targeting-prostatic-acid-phosphatase-pap-in-patients-with-metastatic-castration-resistant-prostate-cancer-mcrpc-using-sipuleucel-t-and-a-dna-vaccine
#7
Ellen Wargowski, Laura E Johnson, Jens C Eickhoff, Lauren Delmastro, Mary Jane Staab, Glenn Liu, Douglas G McNeel
BACKGROUND: Prostatic acid phosphatase (PAP) is a prostate tumor antigen, and the target of the only FDA-approved anti-tumor vaccine, sipuleucel-T. We have previously reported in two clinical trials that a DNA vaccine encoding PAP (pTVG-HP) could elicit PAP-specific, Th1-biased T cells in patients with PSA-recurrent prostate cancer. In the current pilot trial we sought to evaluate whether this vaccine could augment PAP-specific immunity when used as a booster to immunization with sipuleucel-T in patients with metastatic, castration-resistant prostate cancer (mCRPC)...
March 13, 2018: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/29510745/randomized-phase-ii-trial-of-autologous-dendritic-cell-vaccines-versus-autologous-tumor-cell-vaccines-in-metastatic-melanoma-5-year-follow-up-and-additional-analyses
#8
Robert O Dillman, Andrew N Cornforth, Gabriel I Nistor, Edward F McClay, Thomas T Amatruda, Carol Depriest
BACKGROUND: Despite improved survival following checkpoint inhibitors, there is still a potential role for anti-cancer therapeutic vaccines. Because of biological heterogeneity and neoantigens resulting from each patient's mutanome, autologous tumor may be the best source of tumor-associated antigens (TAA) for vaccines. Ex vivo loading of autologous dendritic cells with TAA may be associated with superior clinical outcome compared to injecting irradiated autologous tumor cells. We conducted a randomized phase II trial to compare autologous tumor cell vaccines (TCV) and autologous dendritic cell vaccines (DCV) loaded with autologous TAA...
March 6, 2018: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/29510739/measuring-multiple-parameters-of-cd8-tumor-infiltrating-lymphocytes-in-human-cancers-by-image-analysis
#9
Keith E Steele, Tze Heng Tan, René Korn, Karma Dacosta, Charles Brown, Michael Kuziora, Johannes Zimmermann, Brian Laffin, Moritz Widmaier, Lorenz Rognoni, Ruben Cardenes, Katrin Schneider, Anmarie Boutrin, Philip Martin, Jiping Zha, Tobias Wiestler
BACKGROUND: Immuno-oncology and cancer immunotherapies are areas of intense research. The numbers and locations of CD8+ tumor-infiltrating lymphocytes (TILs) are important measures of the immune response to cancer with prognostic, pharmacodynamic, and predictive potential. We describe the development, validation, and application of advanced image analysis methods to characterize multiple immunohistochemistry-derived CD8 parameters in clinical and nonclinical tumor tissues. METHODS: Commercial resection tumors from nine cancer types, and paired screening/on-drug biopsies of non-small-cell lung carcinoma (NSCLC) patients enrolled in a phase 1/2 clinical trial investigating the PD-L1 antibody therapy durvalumab (NCT01693562), were immunostained for CD8...
March 6, 2018: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/29510697/distinct-predictive-biomarker-candidates-for-response-to-anti-ctla-4-and-anti-pd-1-immunotherapy-in-melanoma-patients
#10
Priyanka B Subrahmanyam, Zhiwan Dong, Daniel Gusenleitner, Anita Giobbie-Hurder, Mariano Severgnini, Jun Zhou, Michael Manos, Lauren M Eastman, Holden T Maecker, F Stephen Hodi
BACKGROUND: While immune checkpoint blockade has greatly improved clinical outcomes in diseases such as melanoma, there remains a need for predictive biomarkers to determine who will likely benefit most from which therapy. To date, most biomarkers of response have been identified in the tumors themselves. Biomarkers that could be assessed from peripheral blood would be even more desirable, because of ease of access and reproducibility of sampling. METHODS: We used mass cytometry (CyTOF) to comprehensively profile peripheral blood of melanoma patients, in order to find predictive biomarkers of response to anti-CTLA-4 or anti-PD-1 therapy...
March 6, 2018: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/29486799/radiation-and-pd-l-1-treatment-combinations-immune-response-and-dose-optimization-via-a-predictive-systems-model
#11
Yuri Kosinsky, Simon J Dovedi, Kirill Peskov, Veronika Voronova, Lulu Chu, Helen Tomkinson, Nidal Al-Huniti, Donald R Stanski, Gabriel Helmlinger
BACKGROUND: Numerous oncology combination therapies involving modulators of the cancer immune cycle are being developed, yet quantitative simulation models predictive of outcome are lacking. We here present a model-based analysis of tumor size dynamics and immune markers, which integrates experimental data from multiple studies and provides a validated simulation framework predictive of biomarkers and anti-tumor response rates, for untested dosing sequences and schedules of combined radiation (RT) and anti PD-(L)1 therapies...
February 27, 2018: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/29486797/a-randomized-controlled-trial-evaluating-the-efficacy-and-safety-of-bth1677-in-combination-with-bevacizumab-carboplatin-and-paclitaxel-in-first-line-treatment-of-advanced-non-small-cell-lung-cancer
#12
Walburga Engel-Riedel, Jamie Lowe, Paulette Mattson, J Richard Trout, Richard D Huhn, Michele Gargano, Myra L Patchen, Richard Walsh, My My Trinh, Mariève Dupuis, Folker Schneller
BACKGROUND: BTH1677, a beta-glucan pathogen-associated molecular pattern molecule, drives an anti-cancer immune response in combination with oncology antibody therapies. This phase II study explored the efficacy, pharmacokinetics (PK), and safety of BTH1677 combined with bevacizumab/carboplatin/paclitaxel in patients with untreated advanced non-small cell lung cancer (NSCLC). METHODS: Patients were randomized to the BTH1677 arm (N = 61; intravenous [IV] BTH1677, 4 mg/kg, weekly; IV bevacizumab, 15 mg/kg, once each 3-week cycle [Q3W]; IV carboplatin, 6 mg/mL/min Calvert formula area-under-the-curve, Q3W; and IV paclitaxel, 200 mg/m2 , Q3W) or Control arm (N = 31; bevacizumab/carboplatin/paclitaxel as above)...
February 27, 2018: Journal for Immunotherapy of Cancer
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
#13
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
#14
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
#15
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
#16
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
#17
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
#18
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
#19
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
#20
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
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