Journal of Immunotherapy and Precision Oncology最新文献

{"title":"Highlights on Ocular Toxicity of Immune Checkpoint Inhibitors at a US Tertiary Cancer Center.","authors":"Anam A Mazharuddin,&nbsp;Andrew T Whyte,&nbsp;Dan S Gombos,&nbsp;Nimisha Patel,&nbsp;Azadeh Razmandi,&nbsp;Amina L Chaudhry,&nbsp;Nagham S Al-Zubidi","doi":"10.36401/JIPO-22-14","DOIUrl":"https://doi.org/10.36401/JIPO-22-14","url":null,"abstract":"<p><strong>Introduction: </strong>Immune checkpoint inhibitors (ICIs) have improved prognosis in advanced malignancies; however, they may be associated with extensive ocular immune-related adverse events (irAEs) that are sight threatening. Our study aimed to identify the presentation, characteristics, management, and clinical outcomes of ocular irAEs.</p><p><strong>Methods: </strong>In this retrospective, observational case series, we reviewed the medical records of 1280 patients at a large US tertiary cancer center between 2010 and 2020.</p><p><strong>Results: </strong>We identified 130 patients who presented with ocular irAEs (10%) with 69 males (53%) and 61 females (47%). The mean time to toxicity was 6.1 months. Adverse events include corneal toxicity (31%), neuro-ophthalmic (14%), uveitis and scleritis (13%), retinopathy (13%), periocular disorders (11%), and others. IrAEs occurred most frequently with nivolumab (26%). Most ocular irAEs were treated with topical therapy. Advanced cases required systemic corticosteroids and even cessation of ICIs.</p><p><strong>Conclusion: </strong>Our cohort is a large case series highlighting the increased potential of ocular toxicity associated with ICIs. Prompt recognition and management of ocular irAEs can minimize their effect.</p>","PeriodicalId":16081,"journal":{"name":"Journal of Immunotherapy and Precision Oncology","volume":"5 4","pages":"98-104"},"PeriodicalIF":0.0,"publicationDate":"2022-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/1b/29/i2590-017X-5-4-98.PMC9714419.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10364208","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction Notice for \"Cancer Epigenomics and Beyond: Advancing the Precision Oncology Paradigm\" by Daniel Y Lee.","authors":"","doi":"10.36401/JIPO-22-X2","DOIUrl":"https://doi.org/10.36401/JIPO-22-X2","url":null,"abstract":"<p><p>[This corrects the article DOI: 10.36401/JIPO-20-18.].</p>","PeriodicalId":16081,"journal":{"name":"Journal of Immunotherapy and Precision Oncology","volume":"5 4","pages":"161"},"PeriodicalIF":0.0,"publicationDate":"2022-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9714414/pdf/i2590-017X-5-4-161.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10738504","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Guest Editor and Reviewer Acknowledgments: 2022.","authors":"","doi":"10.36401/JIPO-22-X5","DOIUrl":"https://doi.org/10.36401/JIPO-22-X5","url":null,"abstract":"","PeriodicalId":16081,"journal":{"name":"Journal of Immunotherapy and Precision Oncology","volume":"5 4","pages":"162"},"PeriodicalIF":0.0,"publicationDate":"2022-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/61/6e/i2590-017X-5-4-162.PMC9714417.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10738505","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Of Mice, Not Men: When the Bench-to-Bedside Bridge Is Broken.","authors":"Mina Nikanjam,&nbsp;Shumei Kato,&nbsp;Razelle Kurzrock","doi":"10.36401/JIPO-22-X3","DOIUrl":"https://doi.org/10.36401/JIPO-22-X3","url":null,"abstract":"when the bench-to-bedside bridge is broken","PeriodicalId":16081,"journal":{"name":"Journal of Immunotherapy and Precision Oncology","volume":"5 4","pages":"87-89"},"PeriodicalIF":0.0,"publicationDate":"2022-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/18/64/i2590-017X-5-4-87.PMC9714416.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10372118","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Tumor Infiltrating Lymphocyte Expression of PD-1 Predicts Response to Anti-PD-1/PD-L1 Immunotherapy.","authors":"Nicholas J Bevins, Ryosuke Okamura, Meagan Montesion, Jacob J Adashek, Aaron M Goodman, Razelle Kurzrock","doi":"10.36401/JIPO-22-9","DOIUrl":"10.36401/JIPO-22-9","url":null,"abstract":"<p><strong>Introduction: </strong>Many studies have focused on the role of programmed death receptor ligand 1 (PD-L1) expression in predicting immunotherapy outcomes. Limited clinical data are available regarding the role of programmed death receptor 1 (PD-1; the PD-L1 receptor) expressing tumor-infiltrating lymphocytes (TILs) in PD-1/PD-L1 antibody responsiveness. However, preclinical studies demonstrate that TILs expressing PD-1 contribute to tumor immune evasion.</p><p><strong>Methods: </strong>This study analyzed the association between TIL-PD-1 status and outcome after immune checkpoint blockade (ICB) therapy. We evaluated 123 patients with various solid tumors treated with monoclonal antibodies targeting the PD-1/PD-L1 signaling axis. Additionally, 8706 solid tumor specimens were assessed for TIL-PD-1 and tumor mutational burden (TMB) status.</p><p><strong>Results: </strong>The presence of PD-1-expressing TILs in tumors was associated with increased median progression-free survival (7.0 vs 1.9 months; <i>p</i> = 0.006) and overall survival (18.1 vs 8.0 months; <i>p</i> = 0.04) after treatment with ICB. TIL-PD-1-positive patients had an objective response rate (ORR) of 41% (95% CI, 24-61; <i>N</i> = 12/29) compared with 17% (95% CI, 4-43; <i>N</i> = 3/17) for TIL-PD-1-negative patients (<i>p</i> = 0.18). Analyzed as continuous variables, TIL-PD-1 and TMB showed a weak correlation in 8706 solid tumor samples (Pearson <i>r</i> = 0.074); when analyzed as categorical variables (cutoffs: TIL-PD-1 ≥ 1% and TMB ≥ 10 mutations/Mb), the two variables are correlated (<i>p</i> < 0.0001). TIL-PD-1-positive status is also associated with enrichment of pathologic variants within several genes, most notably <i>TP53</i> (adjusted <i>p</i> < 0.05).</p><p><strong>Conclusion: </strong>TIL-PD-1 positivity in tumors (≥ 1%) is associated with significantly longer progression-free and overall survival after ICB. <b>ClinicalTrials.gov ID: NCT02478931</b>.</p>","PeriodicalId":16081,"journal":{"name":"Journal of Immunotherapy and Precision Oncology","volume":"5 4","pages":"90-97"},"PeriodicalIF":0.0,"publicationDate":"2022-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/3f/fe/i2590-017X-5-4-90.PMC9714418.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10371693","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targeting <i>KRAS</i>: Crossroads of Signaling and Immune Inhibition.","authors":"Shumei Kato,&nbsp;Yu Fujiwara,&nbsp;David S Hong","doi":"10.36401/JIPO-22-5","DOIUrl":"https://doi.org/10.36401/JIPO-22-5","url":null,"abstract":"<p><p>Mutations of <i>RAS</i> are commonly seen in human cancers, especially in lung, colorectal, and pancreatic adenocarcinoma. Despite huge effort for decades, targeting <i>RAS</i> mutations has been \"undruggable\" because of the molecular instability of RAS protein inhibition. However, the recent discovery of the <i>KRAS</i> G12C inhibitor paved the way to expand therapeutic options for patients with cancer harboring the <i>KRAS</i> G12C mutation. At the same time, the successful development of immune checkpoint inhibitors (ICIs) drastically changed the paradigm of cancer treatment and resulted in a better understanding of the tumor immune microenvironment in patients with <i>KRAS</i>-mutant cancer. This review describes the following: the clinical characteristics of cancer with <i>KRAS</i> mutation; successful development of the <i>KRAS</i> G12C inhibitor and its impact on the tumor immune microenvironment; and potential new avenues such as the combination strategy using <i>KRAS</i> inhibitor and ICI, with preclinical and clinical rationales for overcoming resistance to inhibition of <i>KRAS</i> to improve therapeutic efficacy for patients with cancer harboring <i>KRAS</i> mutations.</p>","PeriodicalId":16081,"journal":{"name":"Journal of Immunotherapy and Precision Oncology","volume":" ","pages":"68-78"},"PeriodicalIF":0.0,"publicationDate":"2022-08-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/2a/ca/i2590-017X-5-3-68.PMC9390702.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33443554","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Combination Immune Checkpoint Blockade Regimens for Previously Untreated Metastatic Renal Cell Carcinoma: The Winship Cancer Institute of Emory University Experience.","authors":"Dylan J Martini,&nbsp;T Anders Olsen,&nbsp;Subir Goyal,&nbsp;Yuan Liu,&nbsp;Sean T Evans,&nbsp;Emilie Elise Hitron,&nbsp;Greta Anne Russler,&nbsp;Lauren Yantorni,&nbsp;Sarah Caulfield,&nbsp;Jacqueline T Brown,&nbsp;Jamie M Goldman,&nbsp;Bassel Nazha,&nbsp;Bradley C Carthon,&nbsp;Wayne B Harris,&nbsp;Omer Kucuk,&nbsp;Viraj A Master,&nbsp;Mehmet Asim Bilen","doi":"10.36401/JIPO-22-2","DOIUrl":"https://doi.org/10.36401/JIPO-22-2","url":null,"abstract":"<p><strong>Introduction: </strong>There are three combination immune checkpoint inhibitor (ICI)-based regimens in the first-line setting for metastatic renal cell carcinoma (mRCC). Currently, there is limited real-world data for clinical outcomes and toxicity in mRCC patients treated with first-line ICI-based regimens.</p><p><strong>Methods: </strong>We performed a retrospective review of 49 mRCC patients treated with ICI-based combination regimens in the standard of care setting at the Winship Cancer Institute of Emory University from 2015-2020. We collected baseline data from the electronic medical record including demographic information and disease characteristics. Immune-related adverse events (irAEs) were collected from clinic notes and laboratory values. The primary clinical outcomes measured were overall survival (OS), progression-free survival (PFS), and objective response rate (ORR).</p><p><strong>Results: </strong>The median age was 65 years, and most patients (80%) were males. The majority were White (86%) and had clear cell RCC (83%). Most patients had an Eastern Cooperative Oncology Group (ECOG) performance status score of 0 (43%) or 1 (45%). Approximately one-half (49%) had at least three sites of distant metastatic disease. Most patients (88%) received nivolumab and ipilimumab. More than one-half (53%) of patients experienced an irAE, with 13 (27%) patients having treatment delayed and 18% discontinuing treatment for toxicity. The median OS was not reached, and the median PFS was 8.0 months per a Kaplan-Meier estimation. More than half of patients (53%) had a PFS > 6 months, and 22% had PFS > 1 year. The ORR was 33% for the entire cohort, and 7% of patients had a complete response.</p><p><strong>Conclusion: </strong>We presented real-world efficacy and toxicity data for front-line ICI combination treatment regimens. The ORR and median PFS were lower in our cohort of patients compared to the available data in the clinical trial setting. This was likely because of more advanced disease in this study. Future studies should provide additional data that will allow comparisons between different ICI combination regimens for untreated mRCC.</p>","PeriodicalId":16081,"journal":{"name":"Journal of Immunotherapy and Precision Oncology","volume":"5 3","pages":"52-57"},"PeriodicalIF":0.0,"publicationDate":"2022-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/b1/d2/i2590-017X-5-3-52.PMC9390705.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10110713","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Immuno-Oncology 360° 8th Annual Event Highlights.","authors":"Danny McCarthy","doi":"10.36401/JIPO-22-X1","DOIUrl":"https://doi.org/10.36401/JIPO-22-X1","url":null,"abstract":"The 8th Annual Immuno-Oncology 3608 (IO3608) event was held March 16–18, 2022, in New York City. IO3608 2022 attracted a gathering of more than 450 attendees, representing industry, academia, and investment; 125þ speakers; 80þ IO topics; and 9þ hours of networking. Day one began with opening remarks from chairs Axel Hoos, MD, PhD, CEO of Scorpion Therapeutics, and James Gulley, MD, PhD, Chief, Genitourinary Malignancies Branch, Director, Medical Oncology Service, Center for Cancer Research, National Cancer Institute, National Institutes of Health. The opening keynote was from Nobel Laureate Gregg Semenza, MD, PhD, Director, Vascular Program, Institute for Cell Engineering, and Professor of Genetic Medicine, at Johns Hopkins University School of Medicine (Figure 1). Dr Semenza discussed his research into hypoxia-inducible factors (HIF) and the impact of HIF inhibition on immunotherapy cancer treatment. Daniel Chen, MD, PhD, Founder, Engenuity Life Sciences, gave the Zeitgeist Talk. Dr Chen provided a broad understanding of the IO landscape a decade after checkpoint inhibitors: what is known, what needs to be known, and how to get there faster. Plenary talks covered discovery phase, translational, and biomarker research. There were two tracks focused on clinical operations and advancements in imaging. Five companies participated in the IO3608 biotech showcase. At the annual IO3608 debate, Kristen Hege, MD, Senior Vice President, Early Clinical Development, Hematology/Oncology and Cell Therapy, Bristol Myers Squibb (BMS), and Bob Valamehr, PhD, Chief Research and Development Officer, Fate Therapeutics, debated whether natural killer cells or T cells were the future for chimeric antigen receptor (CAR) therapy. After day one, several attendees took a guided historical walk of New York City’s first landmark district, Brooklyn Heights. Day two began with a welcome from Dr Gulley and a keynote from Rachel Haurwitz, PhD, CEO of Caribou Biosciences (Figure 2). Dr Haurwitz presented on her company’s use of CRISPR (clustered regularly interspaced Figure 1. Nobel Laureate Gregg Semenza, MD, PhD, Johns Hopkins University, discussed his research into hypoxia-inducible factors (HIF) and the impact of HIF inhibition on immunotherapy cancer treatment.","PeriodicalId":16081,"journal":{"name":"Journal of Immunotherapy and Precision Oncology","volume":" ","pages":"84-86"},"PeriodicalIF":0.0,"publicationDate":"2022-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/96/d0/i2590-017X-5-3-84.PMC9390701.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33443551","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Protein Arginine Methyltransferase 5 (PRMT5) Inhibitors in Oncology Clinical Trials: A review.","authors":"Kavanya Feustel,&nbsp;Gerald S Falchook","doi":"10.36401/JIPO-22-1","DOIUrl":"https://doi.org/10.36401/JIPO-22-1","url":null,"abstract":"<p><p>Protein arginine methyltransferase 5 (PRMT5) inhibitors are a new class of antineoplastic agents showing promising preliminary clinical efficacy. Targeting an enzyme involved in a wide array of cellular and transcriptional pro-oncogenic processes, this class offers multifaceted tumor-suppressive effects. Partial response has been seen in adenoid cystic carcinoma from both GSK3326595 and JNJ-64619178, with four cases of stable disease seen with PRT543. Highly significant is a durable complete response in isocitrate dehydrogenase 1-mutated glioblastoma multiforme with PRT811. Both alone and in combination with existing chemotherapies and immunotherapies, this class shows promising preliminary data, particularly in cancers with splicing mutations and DNA damage repair deficiencies. Further studies are warranted, and there are clinical trials to come whose data will be telling of the efficacy of PRMT5 inhibitors in both hematologic and solid malignancies. The aim of this study is to compile available results of PRMT5 inhibitors in oncology clinical trials.</p>","PeriodicalId":16081,"journal":{"name":"Journal of Immunotherapy and Precision Oncology","volume":" ","pages":"58-67"},"PeriodicalIF":0.0,"publicationDate":"2022-06-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/25/43/i2590-017X-5-3-58.PMC9390703.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33443552","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Oligometastatic Squamous Cell Transformation From Metastatic Prostate Adenocarcinoma Treated With Systemic and Focal Therapy: A Case Report.","authors":"Karen Autio,&nbsp;Sean McBride","doi":"10.36401/JIPO-22-4","DOIUrl":"https://doi.org/10.36401/JIPO-22-4","url":null,"abstract":"<p><p>Transformation to squamous cell carcinoma (SCC) after initial treatment of a primary prostate adenocarcinoma is rare and typically results in rapid treatment-refractory disease progression and death. Here, we present a case of a 70-year-old man who was initially treated with prostatectomy and radiotherapy, and later developed bone metastases. After commencing systemic therapy with androgen deprivation therapy (ADT) and apalutamide, his prostate-specific antigen (PSA) declined to undetectable levels, yet short-interval imaging demonstrated oligo-progression at T4, with biopsy specimen demonstrating pure SCC. Molecular profiling of both the primary prostate tumor and T4 demonstrated alterations in <i>TMPRSS2-ERG</i>, <i>TP53</i>, and <i>FOXA1</i> confirming site of origin, with loss of <i>RNF43</i> in the squamous metastasis. He was treated with stereotactic body radiation therapy to the SCC metastasis and continued on ADT and apalutamide with stable disease for a year post-radiation. This case highlights the importance of imaging to detect non-PSA-producing metastatic disease, the utility of radiation therapy in oligo-progression, and use of molecular profiling to provide insights into the pathogenesis of histologic transformation.</p>","PeriodicalId":16081,"journal":{"name":"Journal of Immunotherapy and Precision Oncology","volume":" ","pages":"79-83"},"PeriodicalIF":0.0,"publicationDate":"2022-06-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/3b/7e/i2590-017X-5-3-79.PMC9390704.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33443553","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}