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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/28817445/the-safety-of-pembrolizumab-in-metastatic-melanoma-and-rheumatoid-arthritis
#2
Akshjot Puri, Jade Homsi
Immunotherapy has been in use for the treatment of melanoma since a very long time, but only recently have the cytotoxic T-lymphocyte antigen-4 (CTLA-4) antibody ipilimumab and programmed cell death-1 inhibitors such as nivolimumab and pembrolizumab been shown to induce marked improvements in survival in patients with metastatic melanoma. An important concern arises in terms of the safety of the use of these agents in patients with autoimmune diseases, solid organ transplant recipients on immunosuppression, patients with a history of previous hepatitis B or C, and patients with HIV infections as these patients were excluded from pivotal immunotherapy studies...
August 16, 2017: Melanoma Research
https://www.readbyqxmd.com/read/28816150/phase-1-study-of-ipilimumab-combined-with-whole-brain-radiation-therapy-or-radiosurgery-for-melanoma-patients-with-brain-metastases
#3
Noelle L Williams, Evan J Wuthrick, Hyun Kim, Joshua D Palmer, Shivank Garg, Harriet Eldredge-Hindy, Constantine Daskalakis, Kendra J Feeney, Michael J Mastrangelo, Lyndon J Kim, Takami Sato, Kari L Kendra, Thomas Olencki, David A Liebner, Christopher J Farrell, James J Evans, Kevin D Judy, David W Andrews, Adam P Dicker, Maria Werner-Wasik, Wenyin Shi
PURPOSE: We performed a phase 1 study to determine the maximum tolerable dose and safety of ipilimumab with stereotactic radiosurgery (SRS) or whole brain radiation therapy (WBRT) in patients with brain metastases from melanoma. METHODS AND MATERIALS: Based on the intracranial disease burden, patients underwent WBRT (arm A) or SRS (arm B). The ipilimumab starting dose was 3 mg/kg every 3 weeks, starting on day 3 of WBRT or 2 days after SRS. The ipilimumab dose was escalated to 10 mg/kg using a 2-stage, 3+3 design...
September 1, 2017: International Journal of Radiation Oncology, Biology, Physics
https://www.readbyqxmd.com/read/28783540/survival-of-melanoma-patients-treated-with-targeted-therapy-and-immunotherapy-after-systematic-upfront-control-of-brain-metastases-by-radiosurgery
#4
C Gaudy-Marqueste, A S Dussouil, R Carron, L Troin, N Malissen, A Loundou, S Monestier, S Mallet, M A Richard, J M Régis, J J Grob
BACKGROUND: Targeted therapy (TT) and immunotherapies (ITs) have dramatically improved survival in metastatic melanoma (MM). However, their efficacy on brain metastasis (BM) remains limited and poorly documented. PATIENTS AND METHODS: Retrospective cohort of consecutive MM patients (pts) with BMs, all systematically upfront treated by Gamma-Knife (GK) at first BM and retreated in case of new BMs, from 2010 to 2015 at the time when ipilimumab BRAF ± MEK inhibitors and anti-PD1 were introduced in practice...
August 4, 2017: European Journal of Cancer
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
#5
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/28776411/the-importance-for-immunoregulation-for-long-term-cancer-control
#6
Alberto Fusi, Angus Dalgleish
Immune checkpoint blockades have recently emerged as a breakthrough treatment for solid tumors showing high response rates and long durability. In melanoma, the combination of ipilimumab with nivolumab showed high efficacy. However, still half the patients do not respond to this treatment. In order to increase the therapeutic ratio in melanoma and other cancers, different approaches are under evaluation. Three relevant questions are at the moment driving the research community: how to maximize benefit while minimizing toxicity; how to better identify patients who are more likely to benefit from immunotherapy; how to convert nonresponders into responders...
August 4, 2017: Future Oncology
https://www.readbyqxmd.com/read/28770166/genomic-signature-of-the-natural-oncolytic-herpes-simplex-virus-hf10-and-its-therapeutic-role-in-preclinical-and-clinical-trials
#7
REVIEW
Ibrahim Ragab Eissa, Yoshinori Naoe, Itzel Bustos-Villalobos, Toru Ichinose, Maki Tanaka, Wu Zhiwen, Nobuaki Mukoyama, Taishi Morimoto, Noriyuki Miyajima, Hasegawa Hitoki, Seiji Sumigama, Branko Aleksic, Yasuhiro Kodera, Hideki Kasuya
Oncolytic viruses (OVs) are opening new possibilities in cancer therapy with their unique mechanism of selective replication within tumor cells and triggering of antitumor immune responses. HF10 is an oncolytic herpes simplex virus-1 with a unique genomic structure that has non-engineered deletions and insertions accompanied by frame-shift mutations, in contrast to the majority of engineered OVs. At the genetic level, HF10 naturally lacks the expression of UL43, UL49.5, UL55, UL56, and latency-associated transcripts, and overexpresses UL53 and UL54...
2017: Frontiers in Oncology
https://www.readbyqxmd.com/read/28765062/immune-mediated-neuropathy-following-checkpoint-immunotherapy
#8
REVIEW
Yufan Gu, Alexander M Menzies, Georgina V Long, S L Fernando, G Herkes
Checkpoint immunotherapy has revolutionised cancer therapy and is now standard treatment for many malignancies including metastatic melanoma. Acute inflammatory neuropathies, often labelled as Guillain-Barre syndrome, are an uncommon but potentially severe complication of checkpoint immunotherapy with individual cases described but never characterised as a group. We describe a case of acute sensorimotor and autonomic neuropathy following a single dose of combination ipilimumab and nivolumab for metastatic melanoma...
July 29, 2017: Journal of Clinical Neuroscience: Official Journal of the Neurosurgical Society of Australasia
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
#9
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/28753231/pd-1-inhibitor-associated-lichenoid-inflammation-with-incidental-suprabasilar-acantholysis-or-vesiculation-report-of-four-cases
#10
Shaun Chou, Cathy Zhao, Shelley Ji Eun Hwang, Pablo Fernandez-Penas
BACKGROUND: Immune checkpoint agents targeting Programmed cell death-1 protein (PD1) or Cytotoxic T-Lymphocyte Associated Protein-4 (CTLA-4) receptors are increasingly utilised in treatment of advanced malignancies. However, these immunotherapies are commonly associated with idiosyncratic cutaneous adverse reactions. Thus, recognition and awareness of these reactions are necessary. METHODS: We reviewed the skin biopsies of all patients on anti-PD1 therapy with or without ipilimumab who developed lichenoid inflammation and included those with microscopic suprabasal or intraepidermal clefts...
July 28, 2017: Journal of Cutaneous Pathology
https://www.readbyqxmd.com/read/28751442/towards-precision-radiotherapy-for-use-with-immune-checkpoint-blockers
#11
Claire Vanpouille-Box, Silvia C Formenti, Sandra Demaria
The first evidence that radiation therapy (RT) enhances the efficacy of immune checkpoint blockers (ICBs) was obtained a dozen years ago in a mouse model of metastatic carcinoma refractory to anti-CTLA-4 treatment. At the time, ICBs had just entered clinical testing, an endeavor that culminated in 2011 with the approval of the first anti-CTLA-4 antibody for use in metastatic melanoma patients (ipilimumab). Thereafter, some patients progressing on ipilimumab showed systemic responses only upon receiving radiation to one lesion, confirming clinically the pro-immunogenic effects of radiation...
July 27, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28749795/hepatotoxicity-after-immune-checkpoint-inhibitor-therapy-in-melanoma-natural-progression-and-management
#12
Brandon M Huffman, Lisa A Kottschade, Patrick S Kamath, Svetomir N Markovic
OBJECTIVE: To report the clinical features, treatment, and outcomes of patients with immune checkpoint inhibitor-induced hepatotoxicity. PATIENTS AND METHODS: In this retrospective observational study, we identified patients with metastatic malignant melanoma seen in consultation and/or treated between March 2011 and March 2016. Hepatotoxicity was assessed using the Common Terminology Criteria for Adverse Events, v4.0. RESULTS: Seventeen patients were identified as having any degree of hepatotoxicity by history (grade 1 to 4)...
July 26, 2017: American Journal of Clinical Oncology
https://www.readbyqxmd.com/read/28740933/18f-fdg-pet-response-and-clinical-outcomes-after-stereotactic-body-radiation-therapy-for-metastatic-melanoma
#13
Ryan S Youland, Ann T Packard, Miran J Blanchard, Andrea L Arnett, Gregory A Wiseman, Lisa A Kottschade, Roxana S Dronca, Svetomir N Markovic, Kenneth R Olivier, Sean S Park
BACKGROUND: Clinical data that support stereotactic body radiation therapy (SBRT) metastatic malignant melanoma (MM) are limited. Furthermore, functional imaging with 18F-fludeoxyglucose positron emission tomography (PET) may offer a more accurate post-SBRT assessment. Therefore, we assessed the clinical outcomes and metabolic response of metastatic MM after SBRT. METHODS AND MATERIALS: Patients with MM who were treated with SBRT and had pre- and post-PET scans (>1) were included in this study...
April 2017: Advances in Radiation Oncology
https://www.readbyqxmd.com/read/28738054/ipilimumab-based%C3%A2-therapy-consensus-statement-from-the-faculty-of-the-melanoma-nursing-initiative-on-managing-adverse-events-with-ipilimumab-monotherapy-and-combination-therapy-with-nivolumab
#14
Kathleen M Madden, Brianna Hoffner
BACKGROUND: Ipilimumab (Yervoy®) therapy improves outcomes in patients with resected stage III melanoma, and ipilimumab alone or combined with nivolumab (Opdivo®) does so in those with unresectable or metastatic melanoma. These immunotherapies are associated with immune-related adverse events (irAEs). With prompt recognition and appropriate management, serious sequelae or unnecessary treatment discontinuation can be prevented.
. OBJECTIVES: This article presents consensus statements to guide oncology nurses in the recognition and management of irAEs associated with ipilimumab and nivolumab...
August 1, 2017: Clinical Journal of Oncology Nursing
https://www.readbyqxmd.com/read/28737620/sarcoidosis-following-anti-pd-1-and-anti-ctla-4-therapy-for-metastatic-melanoma
#15
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/28733704/-adverse-effects-of-immunotherapy-clinical-aspects-radiological-and-nuclear-medicine-results
#16
REVIEW
G Widmann, V A Nguyen, J Plaickner, W Jaschke
BACKGROUND: The increasing use of immunotherapy in oncology increases the need for radiologic evaluation of frequent and severe immune-related adverse events. OBJECTIVE: Determination of the incidence and manifestation of radiologic and nuclear medicine findings of immune-related adverse events. MATERIAL AND METHODS: Literature review of clinical and imaging findings of immune-related adverse events induced by the immune checkpoint inhibitors ipilimumab, nivolumab and pembrolizumab...
July 21, 2017: Der Radiologe
https://www.readbyqxmd.com/read/28730266/-malignant-melanoma-current-status
#17
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/28729152/reduced-dose-ipilimumab-with-standard-dose-pembrolizumab-is-less-more
#18
Michael Postow
No abstract text is available yet for this article.
July 17, 2017: Lancet Oncology
https://www.readbyqxmd.com/read/28729151/standard-dose-pembrolizumab-in-combination-with-reduced-dose-ipilimumab-for-patients-with-advanced-melanoma-keynote-029-an-open-label-phase-1b-trial
#19
Georgina V Long, Victoria Atkinson, Jonathan S Cebon, Michael B Jameson, Bernie M Fitzharris, Catriona M McNeil, Andrew G Hill, Antoni Ribas, Michael B Atkins, John A Thompson, Wen-Jen Hwu, F Stephen Hodi, Alexander M Menzies, Alexander D Guminski, Richard Kefford, Benjamin Y Kong, Babak Tamjid, Archana Srivastava, Anna J Lomax, Mohammed Islam, Xinxin Shu, Scot Ebbinghaus, Nageatte Ibrahim, Matteo S Carlino
BACKGROUND: Reduced-dose nivolumab in combination with standard-dose ipilimumab improves objective response and progression-free survival compared with standard-dose ipilimumab alone, but increases toxicity. We assessed the safety and anti-tumour activity of standard-dose pembrolizumab in combination with reduced-dose ipilimumab. METHODS: In this open-label, phase 1b trial, we recruited patients from 12 medical centres in Australia, New Zealand, and the USA. Eligible patients were aged at least 18 years, had advanced melanoma, had an Eastern Coooperative Oncology Group performance status of 0 or 1, had measurable disease according to the Response Evaluation Criteria in Solid Tumors (RECIST) version 1...
July 17, 2017: Lancet Oncology
https://www.readbyqxmd.com/read/28725434/regression-of-multifocoal-in-transit-melanoma-metastases-after-palliative-resection-of-dominant-masses-and-2%C3%A2-years-after-treatment-with-ipilimumab
#20
Raphael B Moreira, Lana Hamieh, Evisa Gjini, Ana Lako, Katherine M Krajewski, Charles H Yoon, Patrick A Ott
BACKGROUND: Spontaneous regression of metastatic melanoma and delayed responses more than one year after treatment with ipilimumab are rarely seen. CASE PRESENTATION: Here, we present the case of a patient with in transit metastases from cutaneous melanoma on his right lower extremity who achieved complete regression of all metastatic lesions 13 months after the first of two consecutive palliative resections of dominant masses and more than two years after treatment with ipilimumab...
2017: Journal for Immunotherapy of Cancer
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