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https://www.readbyqxmd.com/read/29784745/updates-to-the-management-of-kidney-cancer
#1
Eric Jonasch
Several updates were made to the 2018 NCCN Guidelines for Kidney Cancer. Adjuvant sunitinib is the first adjuvant therapy to be endorsed by the panel for patients with stage II and III clear cell histology renal cell carcinoma (RCC; category 2B). A promising new treatment-ipilimumab plus nivolumab for patients at intermediate and poor risk in the frontline setting-was added to the guidelines as well. Cabozantinib was added as a first-line option for poor- and intermediate-risk patients with advanced RCC.
May 2018: Journal of the National Comprehensive Cancer Network: JNCCN
https://www.readbyqxmd.com/read/29782188/an-evaluation-of-nivolumab-for-the-treatment-of-metastatic-renal-cell-carcinoma
#2
Kevin Zarrabi, Shenhong Wu
The treatment paradigm for metastatic renal cell carcinoma (mRCC) has undergone a revolution with the rapid market approval of multiple agents over a three-year period. The immunogenicity of RCC provided the biological rationale to assess the clinical efficacy of nivolumab, an immune checkpoint inhibitor. Nivolumab is approved for second-line treatment after failure of angiogenesis targeted therapy and in combination therapy with ipilimumab for previously untreated intermediate or poor-risk advanced renal cell carcinoma...
May 21, 2018: Expert Opinion on Biological Therapy
https://www.readbyqxmd.com/read/29778737/cancer-immunotherapy-efficacy-and-patients-sex-a-systematic-review-and-meta-analysis
#3
Fabio Conforti, Laura Pala, Vincenzo Bagnardi, Tommaso De Pas, Marco Martinetti, Giuseppe Viale, Richard D Gelber, Aron Goldhirsch
BACKGROUND: Despite the acknowledged sex-related dimorphism in immune system response, little is known about the effect of patients' sex on the efficacy of immune checkpoint inhibitors as cancer treatments. We did a systematic review and meta-analysis to assess the heterogeneity of immune checkpoint inhibitor efficacy between men and women. METHODS: We systematically searched PubMed, MEDLINE, Embase, and Scopus, from database inception to Nov 30, 2017, for randomised controlled trials of immune checkpoint inhibitors (inhibitors of PD-1, CTLA-4, or both) that had available hazard ratios (HRs) for death according to patients' sex...
May 16, 2018: Lancet Oncology
https://www.readbyqxmd.com/read/29775689/biomarkers-for-checkpoint-inhibition-in-hematologic-malignancies
#4
REVIEW
Djordje Atanackovic, Tim Luetkens
In the past few years we have seen remarkable paradigm shifts in the treatment of many solid tumors due to the introduction of inhibitors targeting immune checkpoints such as PD-1/PD-L1 and CTLA-4. Recent results indicate that checkpoint inhibition also represents a very promising approach for certain types of hematologic malignancies. Unfortunately, treatment with checkpoint inhibitors is also associated with substantial toxicities and high costs and only a subset of patients appears to derive clinical benefit from these treatments...
May 15, 2018: Seminars in Cancer Biology
https://www.readbyqxmd.com/read/29774560/high-resolution-separation-of-monoclonal-antibodies-mixtures-and-their-charge-variants-by-an-alternative-and-generic-cze-method
#5
Alexandre Goyon, Yannis Nicolas Francois, Olivier Colas, Alain Beck, Jean Luc Veuthey, Davy Guillarme
The determination of mAb critical quality attributes (CQA) is crucial for their successful application in health diseases. A generic CZE method was developed for the high-resolution separation of various mAb charge variants, which are often recognized as important CQA. A dynamic coating of the capillary was obtained with polyethylene oxide (PEO), whereas Bis-Tris allowed the analysis of mAbs under native conditions at pH 7.0. The effect of PEO and Bis-Tris concentrations, as well as the nature of the acidic counter ion on the method performance were systematically studied...
May 17, 2018: Electrophoresis
https://www.readbyqxmd.com/read/29772919/erythema-nodosum-as-the-initial-presentation-of-nivolumab-induced-sarcoidosis-like-reaction
#6
Alexandre Laroche, Evelyn Alarcon Chinchilla, Emilie Bourgeault, Marc-André Doré
BACKGROUND: We report a case of nivolumab-related sarcoidosis-like syndrome that initially presented with erythema nodosum. Sarcoidosis development has been described in single and combination immunotherapy. CASE PRESENTATION: A 68-year-old white woman with metastatic ocular amelanotic choroid melanoma was treated with nivolumab. The patient developed histologically confirmed erythema nodosum lesions and pulmonary granuloma sarcoidosis. Nivolumab was discontinued and the patient started ipilimumab therapy...
May 1, 2018: Journal of Cutaneous Medicine and Surgery
https://www.readbyqxmd.com/read/29769383/incidence-of-thyroid-function-test-abnormalities-in-patients-receiving-immune-checkpoint-inhibitors-for-cancer-treatment
#7
Nisha Subhash Patel, Anais Oury, Gregory A Daniels, Lyudmila Bazhenova, Sandip Pravin Patel
BACKGROUND: With the advent of immune-checkpoint inhibitor (ICI) therapy (anti-CTLA-4, anti-PD-1), immune-related adverse events such as thyroid function test abnormalities (TFTAs) are common, with a reported incidence range of 2%-15% depending upon the ICI used. The aim of this study is to describe the incidence of TFTAs retrospectively in patients who received ICI therapy. METHODS: A total of 285 patients were reviewed (178 male, 107 female; 16-94 years of age), of whom 218 had no baseline TFTAs, 61 had baseline TFTAs, and 6 had a history of thyroidectomy (excluded)...
May 16, 2018: Oncologist
https://www.readbyqxmd.com/read/29769148/current-landscape-and-future-of-dual-anti-ctla4-and-pd-1-pd-l1-blockade-immunotherapy-in-cancer-lessons-learned-from-clinical-trials-with-melanoma-and-non-small-cell-lung-cancer-nsclc
#8
REVIEW
Young Kwang Chae, Ayush Arya, Wade Iams, Marcelo R Cruz, Sunandana Chandra, Jaehyuk Choi, Francis Giles
Immunotherapy is among the most rapidly evolving treatment strategies in oncology. The therapeutic potential of immune-checkpoint inhibitors is exemplified by the recent hail of Food and Drug Administration (FDA) approvals for their use in various malignancies. Continued efforts to enhance outcomes with immunotherapy agents have led to the formulation of advanced treatment strategies. Recent evidence from pre-clinical studies evaluating immune-checkpoint inhibitors in various cancer cell-lines has suggested that combinatorial approaches may have superior survival outcomes compared to single-agent immunotherapy regimens...
May 16, 2018: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/29766492/nivolumab-versus-ipilimumab-in-the-treatment-of-advanced-melanoma-a-critical-appraisal
#9
M T Wan, M E Ming
AIM: To show whether either nivolumab in combination with ipilimumab or nivolumab monotherapy vs. ipilimumab monotherapy extends overall survival (OS) or progression-free survival (PFS) in adults with previously untreated, advanced melanoma. SETTING AND DESIGN: The trial was conducted at 137 sites in 21 countries. Randomization (n = 945; 1 : 1 : 1 ratio) was stratified according to metastasis stage, BRAF mutation status and programmed death ligand 1 status. STUDY EXPOSURE: Adults were randomized to one of the following: nivolumab plus ipilimumab every 3 weeks for four doses, followed by nivolumab every 2 weeks; nivolumab every 2 weeks plus placebo; or ipilimumab every 3 weeks for four doses plus placebo...
May 15, 2018: British Journal of Dermatology
https://www.readbyqxmd.com/read/29764498/talimogene-laherparepvec-combined-with-anti-pd-1-based-immunotherapy-for-unresectable-stage-iii-iv-melanoma-a-case-series
#10
Lillian Sun, Pauline Funchain, Jung Min Song, Patricia Rayman, Charles Tannenbaum, Jennifer Ko, Michael Mcnamara, C Marcela Diaz-Montero, Brian Gastman
BACKGROUND: Talimogene Laherparepvec (T-VEC) is an oncolytic virus approved as an intratumoral therapy for treating unresectable stage IIIB-IV metastatic melanoma. The mechanisms of action for T-VEC and checkpoint inhibitor are highly complementary. Recent studies have shown that combining checkpoint inhibitor therapy with T-VEC injection can lead to improved response rates for stage IIIB-IV melanoma patients. METHODS: We reviewed 10 consecutive cases of stage IIIC to stage IVM1b melanoma patients that received T-VEC plus checkpoint inhibitor(s) therapy (pembrolizumab, ipilimumab/nivolumab, or nivolumab) treated between June 2016 and August 2017 at the Cleveland Clinic with a median follow-up of 7 months (range: 4 to 13 months)...
May 16, 2018: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/29763618/genomic-features-of-response-to-combination-immunotherapy-in-lung-cancer
#11
Martin Früh, Solange Peters
In this issue of Cancer Cell, Hellmann et al. describe in two clinical trials the importance of tumor mutational burden as an independent predictive marker for outcomes with combination nivolumab plus ipilimumab as first-line therapy in metastatic non-small-cell lung cancer and in relapsed small-cell lung cancer.
May 14, 2018: Cancer Cell
https://www.readbyqxmd.com/read/29755699/sequential-immunotherapy-in-a-patient-with-primary-refractory-hodgkin-lymphoma-and-novel-mutations
#12
Richard Greil, Lisa Pleyer, Bettina Jansko, Carmen Feierabend, Lukas Rettenbacher, Olga Stiefel, Christoph Rass, Patrick Morre, Daniel Neureiter, Sigrun Greil-Ressler
Primary resistant Hodgkin lymphoma is an aggressive disease with few treatment options and short survival. Neoplastic cells of classical Hodgkin lymphoma are heavily dependent on microenvironmental stimuli, regularly express PD-L1, and a relevant proportion of relapsed patients is sensitive to blocking of the PD1/PD-L1 axis. However, response duration is limited and further treatment options are unknown but urgently needed. We report a case of a patient without relevant response to five subsequent chemotherapy regimens who immediately and dramatically responded to an anti-PD1 mab...
April 17, 2018: Oncotarget
https://www.readbyqxmd.com/read/29747688/immune-checkpoint-inhibitor-induced-diarrhea-and-colitis-in-patients-with-advanced-malignancies-retrospective-review-at-md-anderson
#13
Yinghong Wang, Hamzah Abu-Sbeih, Emily Mao, Noman Ali, Faisal Shaukat Ali, Wei Qiao, Phillip Lum, Gottumukkala Raju, Gladis Shuttlesworth, John Stroehlein, Adi Diab
BACKGROUND: Immune checkpoint inhibitors (ICPIs) are gaining increasing popularity as an efficacious treatment for advanced malignancies. ICPI treatment can be complicated by diarrhea and colitis. Systemic steroids are the first line treatment. Infliximab is reserved for severe refractory cases. We aimed to assess the impact of ICPI-induced diarrhea and colitis and their immunosuppressive treatment on patients' outcomes. METHODS: This retrospective analysis was conducted in 327 cancer patients who received ICPIs between 2011 and 2017...
May 11, 2018: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/29743117/a-robust-response-to-combination-immune-checkpoint-inhibitor-therapy-in-hpv-related-small-cell-cancer-a-case-report
#14
Won Jin Ho, Lisa Rooper, Sarah Sagorsky, Hyunseok Kang
BACKGROUND: Human papillomavirus-related small cell carcinoma of the head and neck is an extremely rare, aggressive subtype with poor outcomes. Therapeutic options are limited and are largely adopted from small cell lung cancer treatment paradigms. CASE PRESENTATION: This report describes a 69-year old male who was diagnosed of HPV-related oropharyngeal cancer with mixed small cell and squamous cell pathology which was clinically aggressive and progressed through multimodal platinum-based therapies...
May 9, 2018: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/29743050/unmasking-of-intracranial-metastatic-melanoma-during-ipilimumab-nivolumab-therapy-case-report-and-literature-review
#15
Marin A McDonald, Parag Sanghvi, Julie Bykowski, Gregory A Daniels
BACKGROUND: While data from several studies over the last decade has demonstrated that introduction of immunologic checkpoint blockage therapy with anti-CTLA-4/PD-1 drugs leads to improved survival in metastatic melanoma patients, relatively little is known about brain-specific therapeutic response and adverse events in the context of immunotherapeutic treatment of intracranial disease. Here we report two independent cases of new intracranial metastases presenting after initiation of combined checkpoint blockade Ipilimumab and Nivolumab for recurrent metastatic melanoma in the context of positive systemic disease response...
May 9, 2018: BMC Cancer
https://www.readbyqxmd.com/read/29742520/ipilimumab-nivolumab-related-opsoclonus-myoclonus-ataxia-syndrome-variant-in-a-patient-with-malignant-pleural-mesothelioma
#16
Bradley Maller, Edwin Peguero, Tawee Tanvetyanon
INTRODUCTION: Ipilimumab and nivolumab are immune-checkpoint inhibitors commonly used for melanoma. The combination is being investigated for its efficacy against several types of cancer, including malignant pleural mesothelioma. Although immune-related adverse events have been reported in patients receiving immune-checkpoint inhibitors, opsoclonus-myoclonus-ataxia syndrome has never been previously described. CASE PRESENTATION: We describe a 74-year-old male with malignant pleural mesothelioma who presented with opsoclonus and marked truncal ataxia ∼10 weeks following immunotherapy with ipilimumab and nivolumab...
May 8, 2018: Journal of Immunotherapy
https://www.readbyqxmd.com/read/29731394/tumor-mutational-burden-and-efficacy-of-nivolumab-monotherapy-and-in-combination-with-ipilimumab-in-small-cell-lung-cancer
#17
Matthew D Hellmann, Margaret K Callahan, Mark M Awad, Emiliano Calvo, Paolo A Ascierto, Akin Atmaca, Naiyer A Rizvi, Fred R Hirsch, Giovanni Selvaggi, Joseph D Szustakowski, Ariella Sasson, Ryan Golhar, Patrik Vitazka, Han Chang, William J Geese, Scott J Antonia
Durable responses and encouraging survival have been demonstrated with immune checkpoint inhibitors in small-cell lung cancer (SCLC), but predictive markers are unknown. We used whole exome sequencing to evaluate the impact of tumor mutational burden on efficacy of nivolumab monotherapy or combined with ipilimumab in patients with SCLC from the nonrandomized or randomized cohorts of CheckMate 032. Patients received nivolumab (3 mg/kg every 2 weeks) or nivolumab plus ipilimumab (1 mg/kg plus 3 mg/kg every 3 weeks for four cycles, followed by nivolumab 3 mg/kg every 2 weeks)...
April 21, 2018: Cancer Cell
https://www.readbyqxmd.com/read/29724044/mechanisms-of-intrinsic-tumor-resistance-to-immunotherapy
#18
REVIEW
John Rieth, Subbaya Subramanian
An increased understanding of the interactions between the immune system and tumors has opened the door to immunotherapy for cancer patients. Despite some success with checkpoint inhibitors including ipilimumab, pembrolizumab, and nivolumab, most cancer patients remain unresponsive to such immunotherapy, likely due to intrinsic tumor resistance. The mechanisms most likely involve reducing the quantity and/or quality of antitumor lymphocytes, which ultimately are driven by any number of developments: tumor mutations and adaptations, reduced neoantigen generation or expression, indoleamine 2,3-dioxygenase (IDO) overexpression, loss of phosphatase and tensin homologue (PTEN) expression, and overexpression of the Wnt⁻β-catenin pathway...
May 2, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29722744/the-mayo-clinic-experience-with-the-neurological-complications-of-the-ctla-4-inhibitor-ipilimumab
#19
Michael W Ruff, Michelle L Mauermann
Neurological complications are an increasingly recognized complication of the use of the immune checkpoint inhibitors in the treatment of solid tumors. Ipilimumab is a monoclonal antibody against cytotoxic T-lymphocyte antigen-4, an immune checkpoint inhibitor that suppresses T-cell effector function. The clinical spectrum of ipilimumab-associated neurological complications and optimum treatment approach is not established. We describe our institution's experience with ipilimumab and illustrate 2 cases of presumed autoimmune neurological phenomenon resulting from its use...
May 2018: Neurologist
https://www.readbyqxmd.com/read/29722737/role-of-immune-checkpoint-inhibitors-in-small-cell-lung-cancer
#20
Maryann R Cooper, Abdullah M Alrajhi, Cheryl R Durand
BACKGROUND: Small cell lung cancer (SCLC) accounts for approximately 13% of all lung cancer diagnoses each year. SCLC is characterized by a rapid doubling time, early metastatic spread, and an unfavorable prognosis overall. AREAS OF UNCERTAINTY: Most patients with SCLC will respond to initial treatment; however, the majority will experience a disease recurrence and response to second-line therapies is poor. Immune checkpoint inhibitors may be an option given the success in other diseases...
May 2018: American Journal of Therapeutics
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