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anti pd 1 melanoma

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https://www.readbyqxmd.com/read/28817755/measuring-toxic-effects-and-time-to-treatment-failure-for-nivolumab-plus-ipilimumab-in-melanoma
#1
Alexander N Shoushtari, Claire F Friedman, Pedram Navid-Azarbaijani, Michael A Postow, Margaret K Callahan, Parisa Momtaz, Katherine S Panageas, Jedd D Wolchok, Paul B Chapman
Importance: Nivolumab plus ipilimumab (nivo + ipi) is a standard treatment of advanced melanoma. Two randomized trials describe high objective response rates by Response Evaluation Criteria in Solid Tumors. The trials assessed toxic effects using the Common Terminology Criteria for Adverse Events (CTCAE), which may underestimate incidence of clinically significant immune-related adverse events (AEs). Objective: To describe detailed toxic effects and time to treatment failure of patients with melanoma treated with nivo + ipi in a prospective cohort...
August 17, 2017: JAMA Oncology
https://www.readbyqxmd.com/read/28815334/clinical-characteristics-of-patient-selection-and-imaging-predictors-of-outcome-in-solid-tumors-treated-with-checkpoint-inhibitors
#2
REVIEW
Sabrina Rossi, Luca Toschi, Angelo Castello, Fabio Grizzi, Luigi Mansi, Egesta Lopci
The rapidly evolving knowledge on tumor immunology and the continuous implementation of immunotherapy in cancer have recently led to the FDA and EMA approval of several checkpoint inhibitors as immunotherapic agents in clinical practice. Anti-CTLA-4, anti-PD-1, and anti-PDL-1 antibodies are becoming standard of care in advanced melanoma, as well as in relapsed or metastatic lung and kidney cancer, demonstrating higher and longer response compared to standard chemotherapy. These encouraging results have fostered the evaluation of these antibodies either alone or in combination with other therapies in several dozen clinical trials for the treatment of multiple tumor types...
August 16, 2017: European Journal of Nuclear Medicine and Molecular Imaging
https://www.readbyqxmd.com/read/28811971/preclinical-immunopet-ct-imaging-using-zr-89-labeled-anti-pd-l1-monoclonal-antibody-for-assessing-radiation-induced-pd-l1-upregulation-in-head-and-neck-cancer-and-melanoma
#3
Masahiro Kikuchi, David A Clump, Raghvendra M Srivastava, Lingyi Sun, Dexing Zeng, Julio A Diaz-Perez, Carolyn J Anderson, W Barry Edwards, Robert L Ferris
Radiation therapy (RT) can induce upregulation of programmed death ligand 1 (PD-L1) on tumor cells or myeloid cells, which may affect response to PD-1-based immunotherapy. PD-L1 upregulation during RT is a dynamic process that has been difficult to monitor during treatment. The aim of this study was to evaluate the RT-induced PD-L1 upregulation in the tumor and its microenvironment using immunoPET/CT imaging of two syngeneic murine tumor models (HPV+ head and neck squamous cell carcinoma (HNSCC) or B16F10 melanoma)...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28803728/distinct-cellular-mechanisms-underlie-anti-ctla-4-and-anti-pd-1-checkpoint-blockade
#4
Spencer C Wei, Jacob H Levine, Alexandria P Cogdill, Yang Zhao, Nana-Ama A S Anang, Miles C Andrews, Padmanee Sharma, Jing Wang, Jennifer A Wargo, Dana Pe'er, James P Allison
Immune-checkpoint blockade is able to achieve durable responses in a subset of patients; however, we lack a satisfying comprehension of the underlying mechanisms of anti-CTLA-4- and anti-PD-1-induced tumor rejection. To address these issues, we utilized mass cytometry to comprehensively profile the effects of checkpoint blockade on tumor immune infiltrates in human melanoma and murine tumor models. These analyses reveal a spectrum of tumor-infiltrating T cell populations that are highly similar between tumor models and indicate that checkpoint blockade targets only specific subsets of tumor-infiltrating T cell populations...
August 9, 2017: Cell
https://www.readbyqxmd.com/read/28799876/melanoma-brain-metastasis-the-impact-of-stereotactic-radiosurgery-braf-mutational-status-and-targeted-and-or-immune-based-therapies-on-treatment-outcome
#5
Rupesh Kotecha, Jacob A Miller, Vyshak A Venur, Alireza M Mohammadi, Samuel T Chao, John H Suh, Gene H Barnett, Erin S Murphy, Pauline Funchain, Jennifer S Yu, Michael A Vogelbaum, Lilyana Angelov, Manmeet S Ahluwalia
OBJECTIVE The goal of this study was to investigate the impact of stereotactic radiosurgery (SRS), BRAF status, and targeted and immune-based therapies on the recurrence patterns and factors associated with overall survival (OS) among patients with melanoma brain metastasis (MBM). METHODS A total of 366 patients were treated for 1336 MBMs; a lesion-based analysis was performed on 793 SRS lesions. The BRAF status was available for 78 patients: 35 had BRAF (mut) and 43 had BRAF wild-type ( BRAF-WT) lesions. The Kaplan-Meier method evaluated unadjusted OS; cumulative incidence analysis determined the incidences of local failure (LF), distant failure, and radiation necrosis (RN), with death as a competing risk...
August 11, 2017: Journal of Neurosurgery
https://www.readbyqxmd.com/read/28789707/checkpoint-inhibitors-in-melanoma-and-early-phase-development-in-solid-tumors-what-s-the-future
#6
EDITORIAL
Paolo A Ascierto, Grant A McArthur
Anti-programmed death (PD)-1 and PD-ligand (L)-1 checkpoint inhibitors have revolutionized the therapy of several cancers. Immunotherapy of cancer can offer long-term durable benefit to patients, is active regardless of tumour histology, has a unique immune-related safety profile, and can be used in combination with other cancer treatments. In addition, recent research has shown that immune-based therapy can be used as adjuvant therapy, that outcomes may be influenced by dose, and that clinical activity is observed in patients with brain metastases...
August 8, 2017: Journal of Translational Medicine
https://www.readbyqxmd.com/read/28776578/negative-immune-checkpoint-regulation-by-vista-a-mechanism-of-acquired-resistance-to-anti-pd-1-therapy-in-metastatic-melanoma-patients
#7
Hojabr Kakavand, Louise A Jackett, Alexander M Menzies, Tuba N Gide, Matteo S Carlino, Robyn P M Saw, John F Thompson, James S Wilmott, Georgina V Long, Richard A Scolyer
Understanding the mechanisms of acquired resistance to anti-PD-1 will allow development of better treatment strategies for cancer patients. This study evaluated potential mechanisms of acquired resistance to anti-PD-1 in longitudinally collected metastatic melanoma patient biopsies. Thirty-four metastatic melanoma biopsies were collected from 16 patients who had initially responded to either anti-PD-1 (n=13) alone or combination of anti-PD-1 and ipilimumab (n=3) and then progressed. Biopsies were taken prior to treatment (PRE, n=12) and following progression of disease (PROG, n=22)...
August 4, 2017: Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc
https://www.readbyqxmd.com/read/28756306/atypical-responses-in-patients-with-advanced-melanoma-lung-cancer-renal-cell-carcinoma-and-other-solid-tumors-treated-with-anti-pd-1-drugs-a-systematic-review
#8
REVIEW
Paola Queirolo, Francesco Spagnolo
Anti-programmed death receptor 1 (PD-1) drugs nivolumab and pembrolizumab were recently approved for the treatment of advanced melanoma and other solid tumors. Atypical patterns of response (i.e. tumor shrinkage or stabilization after initial progression) were observed in about 10% of metastatic melanoma patients treated with anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) drug ipilimumab and were associated with improved survival; however, the rate of atypical response patterns to anti-PD-1 therapy is not clear...
July 19, 2017: Cancer Treatment Reviews
https://www.readbyqxmd.com/read/28754882/a-regulatory-role-for-the-co-chaperone-fkbp51s-in-pd-l1-expression-in-glioma
#9
Paolo D'Arrigo, Michele Russo, Anna Rea, Martina Tufano, Elia Guadagno, Maria Laura Del Basso De Caro, Roberto Pacelli, Felix Hausch, Stefania Staibano, Gennaro Ilardi, Silvia Parisi, Maria Fiammetta Romano, Simona Romano
BACKGROUND: FKBP51 is a co-chaperone with isomerase activity, abundantly expressed in glioma. We previously identified a spliced isoform (FKBP51s) and highlighted a role for this protein in the upregulation of Programmed Death Ligand 1 (PD-L1) expression in melanoma. Because gliomas can express PD-L1 causing a defective host anti-tumoral immunity, we investigated whether FKBP51s was expressed in glioma and played a role in PD-L1 regulation in this tumour. METHODS: We used D54 and U251 glioblastoma cell lines that constitutively expressed PD-L1...
July 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/28750150/are-checkpoint-inhibitors-a-valuable-option-for-metastatic-or-unresectable-vulvar-and-vaginal-melanomas
#10
G Quéreux, S Wylomanski, R Bouquin, M Saint-Jean, L Peuvrel, A C Knol, M Hanf, B Dréno
Immune checkpoint inhibitors might be therapeutic options for unresectable or metastatic melanomas of the vulva and vagina but data available in the literature in these melanomas are very limited (1)(2)(3)(4) . The aim of this retrospective study was to investigate the effect of anti-cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) and anti-programmed death 1 (PD-1) antibodies in patients treated in our Skin Cancer Department for unresectable or metastatic vulvar or vaginal melanoma since 2013. This article is protected by copyright...
July 27, 2017: Journal of the European Academy of Dermatology and Venereology: JEADV
https://www.readbyqxmd.com/read/28746871/the-histone-methyltransferase-ezh2-controls-mechanisms-of-adaptive-resistance-to-tumor-immunotherapy
#11
Daniel Zingg, Natalia Arenas-Ramirez, Dilara Sahin, Rodney A Rosalia, Ana T Antunes, Jessica Haeusel, Lukas Sommer, Onur Boyman
Immunotherapy and particularly immune checkpoint inhibitors have resulted in remarkable clinical responses in patients with immunogenic tumors, although most cancers develop resistance to immunotherapy. The molecular mechanisms of tumor resistance to immunotherapy remain poorly understood. We now show that induction of the histone methyltransferase Ezh2 controls several tumor cell-intrinsic and extrinsic resistance mechanisms. Notably, T cell infiltration selectively correlated with high EZH2-PRC2 complex activity in human skin cutaneous melanoma...
July 25, 2017: Cell Reports
https://www.readbyqxmd.com/read/28743833/therapeutic-vaccine-to-cure-large-mouse-hepatocellular-carcinomas
#12
Zhen Han, De Yang, Anna Trivett, Joost J Oppenheim
Hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide with limited therapeutic options. Here we report the development of a therapeutic vaccination regimen (shortened as 'TheraVac') consisting of intratumoral delivery of high-mobility group nucleosome-binding protein 1 (HMGN1), R848/resiquimod, and one of the checkpoint inhibitors (e.g. anti-CTLA4, anti-PD-L1, or low dose of Cytoxan). C57BL/6 mice harboring large (approximately 1 cm in diameter) established subcutaneous Hepa1-6 hepatomas were cured by intratumoral injections of TheraVac and became tumor-free long-term survivors...
July 18, 2017: Oncotarget
https://www.readbyqxmd.com/read/28737763/melanoma-subtypes-demonstrate-distinct-pd-l1-expression-profiles
#13
Genevieve J Kaunitz, Tricia R Cottrell, Mohammed Lilo, Valliammai Muthappan, Jessica Esandrio, Sneha Berry, Haiying Xu, Aleksandra Ogurtsova, Robert A Anders, Alexander H Fischer, Stefan Kraft, Meg R Gerstenblith, Cheryl L Thompson, Kord Honda, Jonathan D Cuda, Charles G Eberhart, James T Handa, Evan J Lipson, Janis M Taube
PD-L1 expression in the tumor immune microenvironment is recognized as both a prognostic and predictive biomarker in patients with cutaneous melanoma, a finding closely related to its adaptive (IFN-γ-mediated) mechanism of expression. Approximately 35% of cutaneous melanomas express PD-L1, however, the expression patterns, levels, and prevalence in rarer melanoma subtypes are not well described. We performed immunohistochemistry for PD-L1 and CD8 on 200 formalin-fixed paraffin-embedded specimens from patients with acral (n=16), mucosal (n=36), uveal (n=103), and chronic sun-damaged (CSD) (n=45) melanomas (24 lentigo maligna, 13 'mixed' desmoplastic, and 8 'pure' desmoplastic melanomas)...
July 24, 2017: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/28737620/sarcoidosis-following-anti-pd-1-and-anti-ctla-4-therapy-for-metastatic-melanoma
#14
Swathi B Reddy, Jennifer D Possick, Harriet M Kluger, Anjela Galan, Dale Han
Immune checkpoint inhibitors represent the newest treatment for stage IV melanoma. These agents are generally well tolerated, however severe immune-related adverse effects have been noted in a small, but clinically significant percentage of patients. Specifically, sarcoidosis is a known potential complication following anti-CTLA-4 therapy. We present 2 cases of pulmonary and cutaneous sarcoidosis developing in patients with stage IV melanoma. Both patients were treated with ipilimumab and anti-PD-1 therapy, and both experienced good oncologic responses to treatment; neither had evidence of preexisting sarcoidosis...
July 21, 2017: Journal of Immunotherapy
https://www.readbyqxmd.com/read/28730266/-malignant-melanoma-current-status
#15
REVIEW
J K Winkler, K Buder-Bakhaya, A Dimitrakopoulou-Strauss, A Enk, J C Hassel
CLINICAL ISSUE: The incidence of malignant melanoma is continuously increasing. The prognosis of metastatic disease is still limited. STANDARD TREATMENT: Until a few years ago palliative chemotherapy with a limited response rate was the standard treatment for metastatic melanoma. TREATMENT INNOVATIONS: Immunotherapy and targeted therapy provide new treatment options. Immune checkpoint inhibitors have significantly improved the prognosis. DIAGNOSTIC WORK-UP: Regional lymph node sonography, computed tomography (CT) of the neck, chest and abdomen and brain magnetic resonance imaging (MRI) are routinely used...
July 20, 2017: Der Radiologe
https://www.readbyqxmd.com/read/28725431/angiosarcoma-treated-successfully-with-anti-pd-1-therapy-a-case-report
#16
Simran Sindhu, Lana H Gimber, Lee Cranmer, Ali McBride, Andrew S Kraft
BACKGROUND: Angiosarcomas are tumors of malignant endothelial origin that have a poor prognosis with a five-year survival of less than 40%. These tumors can be found in all age groups, but are more common in older patients; with the cutaneous form most common in older white men. Combined modality therapy including surgery and radiation appears to have a better outcome than each modality alone. When metastatic, agents such as liposomal doxorubicin, paclitaxel and ifosfamide have activity but it is short-lived and not curative...
2017: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/28725430/acute-interstitial-nephritis-after-sequential-ipilumumab-nivolumab-therapy-of-metastatic-melanoma
#17
Lea Bottlaender, Anne-Laure Breton, Louis de Laforcade, Frederique Dijoud, Luc Thomas, Stephane Dalle
BACKGROUND: The anti-Programmed Death receptor 1 (anti-PD-1) antibodies nivolumab and pembrolizumab are new treatments in metastatic melanoma. Immunotherapies are best known to be responsible for thrombotic microangiopathy. However, immune interstitial nephritis has been described in a patient treated by nivolumab and ipilimumab concomitantly, and three cases of granulomatous interstitial nephritis have been reported with ipilimumab monotherapy. We report herein a case of acute interstitial immune nephritis in a patient treated with nivolumab after ipilimumab for pulmonary metastatic melanoma...
2017: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/28724802/partially-exhausted-tumor-infiltrating-lymphocytes-predict-response-to-combination-immunotherapy
#18
Kimberly Loo, Katy K Tsai, Kelly Mahuron, Jacqueline Liu, Mariela L Pauli, Priscila M Sandoval, Adi Nosrati, James Lee, Lawrence Chen, Jimmy Hwang, Lauren S Levine, Matthew F Krummel, Alain P Algazi, Michael D Alvarado, Michael D Rosenblum, Adil I Daud
BACKGROUND: Programmed death 1 (PD-1) inhibition activates partially exhausted cytotoxic T lymphocytes (peCTLs) and induces tumor regression. We previously showed that the peCTL fraction predicts response to anti-PD-1 monotherapy. Here, we sought to correlate peCTL and regulatory T lymphocyte (Treg) levels with response to combination immunotherapy, and with demographic/disease characteristics, in metastatic melanoma patients. METHODS: Pretreatment melanoma samples underwent multiparameter flow cytometric analysis...
July 20, 2017: JCI Insight
https://www.readbyqxmd.com/read/28724377/combination-therapy-for-melanoma-with-braf-mek-inhibitor-and-immune-checkpoint-inhibitor-a-mathematical-model
#19
Xiulan Lai, Avner Friedman
BACKGROUND: The B-raf gene is mutated in up to 66% of human malignant melanomas, and its protein product, BRAF kinase, is a key part of RAS-RAF-MEK-ERK (MAPK) pathway of cancer cell proliferation. BRAF-targeted therapy induces significant responses in the majority of patients, and the combination BRAF/MEK inhibitor enhances clinical efficacy, but the response to BRAF inhibitor and to BRAF/MEK inhibitor is short lived. On the other hand, treatment of melanoma with an immune checkpoint inhibitor, such as anti-PD-1, has lower response rate but the response is much more durable, lasting for years...
July 19, 2017: BMC Systems Biology
https://www.readbyqxmd.com/read/28716106/acute-interstitial-nephritis-after-sequential-ipilumumab-nivolumab-therapy-of-metastatic-melanoma
#20
Lea Bottlaender, Anne-Laure Breton, Louis de Laforcade, Frederique Dijoud, Luc Thomas, Stephane Dalle
BACKGROUND: The anti-Programmed Death receptor 1 (anti-PD-1) antibodies nivolumab and pembrolizumab are new treatments in metastatic melanoma. Immunotherapies are best known to be responsible for thrombotic microangiopathy. However, immune interstitial nephritis has been described in a patient treated by nivolumab and ipilimumab concomitantly, and three cases of granulomatous interstitial nephritis have been reported with ipilimumab monotherapy. We report herein a case of acute interstitial immune nephritis in a patient treated with nivolumab after ipilimumab for pulmonary metastatic melanoma...
July 18, 2017: Journal for Immunotherapy of Cancer
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