Journal of Immunotherapy and Precision Oncology最新文献

{"title":"Case Series: EGFR and ROS-1 Co-Occurrence in Advanced Non-Small Cell Lung Cancer.","authors":"Turki Alfayea, Alaa A Salim, Mohammad Alkaiyat, Samah Al-Rehaily","doi":"10.36401/JIPO-23-48","DOIUrl":"https://doi.org/10.36401/JIPO-23-48","url":null,"abstract":"<p><p>Non-small cell lung cancer (NSCLC) is a heterogeneous disease with diverse molecular alterations. Two of the most common genetic abnormalities found in advanced NSCLC are mutations in the epidermal growth factor receptor (<i>EGFR</i>) and rearrangements in the ROS proto-oncogene 1 (<i>ROS-1</i>). Although these two alterations are typically mutually exclusive, there have been reports of their co-occurrence in a small subset of NSCLC patients. The discovery of this comutation has recently become apparent due to the increased use of more sensitive whole genome sequencing. We share our experience with two cases of coexisting <i>EGFR</i> and <i>ROS-1</i> alterations. The first case is a 60-year-old man diagnosed with advanced adenocarcinoma of the lung with metastasis to bone and left adrenal gland. The second case is a 49-year-old woman diagnosed with stage IV lung adenocarcinoma with metastasis to the contralateral lung and diffuse abdominal lymphadenopathy. The first case was treated with osimertinib, and currently has had a stable disease on this medication for more than 3 years. The second case had a short interval of stable disease on osimertinib; then she developed progressive disease with poor response to anti-ROS-1 therapy. We believe patients with advanced NSCLC may have a higher incidence of coalterations, especially in the areas of the world with higher <i>EGFR</i> mutations and in the era of higher usage of whole genome sequencing. The presence of comutations will allow for a good long-term response to anti-EGFR therapy. This highlights the importance of the use of next-generation sequencing whenever possible and considers variant allele frequency as a factor in directing the therapy. There are many other unanswered questions, such as the best treatment sequencing or even the combined targeted therapy approach. This case series may add some information to the current literature.</p>","PeriodicalId":16081,"journal":{"name":"Journal of Immunotherapy and Precision Oncology","volume":"7 4","pages":"300-303"},"PeriodicalIF":0.0,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11541924/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142635752","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":"A Phase Ib Study of Selinexor in Combination with Pembrolizumab in Patients with Metastatic Melanoma.","authors":"Mohamed A Gouda, Bettzy Stephen, Yanyan Tian, Anas Alshawa, Dilichukwu O Chudy Onwugaje, Aya Albittar, Yali Yang, Abdulrazzak Zarifa, Bulent Yilmaz, Serdar Gurses, Ashabari Sprenger, Mohamed H Derbala, Amanda Brink, Jeffrey Andrew How, Justin Moyers, Sarina A Piha-Paul, David S Hong, Funda Meric-Bernstam, Sapna P Patel, Isabella Glitza Oliva","doi":"10.36401/JIPO-24-3","DOIUrl":"10.36401/JIPO-24-3","url":null,"abstract":"<p><p>Immune checkpoint inhibitors (ICIs) have substantially advanced the treatment of patients with malignant melanoma. However, improving therapeutic efficacy requires identifying drug combinations that elicit durable responses without inducing intolerable toxicity. Within that context, selinexor emerges as a possible combination option that has been shown in preclinical studies to enhance the efficacy of ICI therapy. <b>Methods:</b> In this phase 1b study, we investigated selinexor in combination with pembrolizumab in 25 patients with advanced non-uveal melanoma. Patients received selinexor at a dosage of 60 mg taken orally twice weekly, and pembrolizumab intravenously at a dosage of 200 mg every 3 weeks. <b>Results:</b> Despite the high incidence of adverse events (96%), most treatment-related toxicities were manageable with supportive care and dose reductions. The most common adverse events of any grade were nausea (<i>n</i> = 20; 80%), decreased white blood cell count (<i>n</i> = 15; 60%), vomiting (<i>n</i> = 14; 56%), anemia (<i>n</i> = 12; 48%), fatigue (<i>n</i> = 12; 48%), and decreased platelet count (<i>n</i> = 12; 48%). The 10 patients with treatment-naïve evaluable disease had an objective response rate (ORR) of 70% (<i>n</i> = 7, including three patients with complete response), which was significantly higher than that of the 14 patients with prior anti-programmed cell death protein 1 (anti-PD-1) therapy, whose ORR was 7% (<i>n</i> = 1; <i>p</i> = 0.002). Stable disease was observed in two patients (20%) with treatment-naïve disease and seven patients (50%) with prior anti-PD-1 therapy. <b>Conclusion:</b> Selinexor combined with pembrolizumab showed promising antitumor activity in patients with treatment-naïve metastatic melanoma. The toxicity profile of the combination was consistent with that reported for individual agents, with no additional safety concerns.</p>","PeriodicalId":16081,"journal":{"name":"Journal of Immunotherapy and Precision Oncology","volume":"7 4","pages":"247-254"},"PeriodicalIF":3.2,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11541928/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142621974","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":"Images in Immunotherapy and Precision Oncology: Advanced Basal Cell Carcinoma.","authors":"Anagha Deshpande, Javier Munoz, Razelle Kurzrock","doi":"10.36401/JIPO-23-47","DOIUrl":"10.36401/JIPO-23-47","url":null,"abstract":"<p><p>A 62-year-old man presented with a slowly growing, painless lesion on his face. This eventually led to a progressive left-eye vision lesion, and the patient was subsequently diagnosed with advanced basal cell carcinoma (BCC). Of note, BCC involving cranial nerves is extremely rare, making this case unique and important to highlight. Standard treatment options for BCC involve surgery, radiation, or platinum-based chemotherapy. However, targeted therapies such as sonidegib and vismodegib - sonic hedgehog pathway inhibitors - have emerged that have been approved for treating BCC, as have anti-PD1 immunotherapies, such as cemiplimab, with their success likely based on the high tumor mutational burden seen in some of these tumors. Epidermal growth factor receptor (EGFR) inhibitors also serve a role in treating this condition as well. Molecular studies on metastatic/advanced BCC and other rare malignancies may inform treatment therapeutic decisions.</p>","PeriodicalId":16081,"journal":{"name":"Journal of Immunotherapy and Precision Oncology","volume":"7 3","pages":"201-204"},"PeriodicalIF":0.0,"publicationDate":"2024-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11361336/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142108116","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":"Phase 1 Clinical Trials: Challenges and Opportunities in Latin America.","authors":"Mirella Nardo, Camila Bragança Xavier, Fabio Franke","doi":"10.36401/JIPO-23-42","DOIUrl":"10.36401/JIPO-23-42","url":null,"abstract":"","PeriodicalId":16081,"journal":{"name":"Journal of Immunotherapy and Precision Oncology","volume":"7 3","pages":"168-170"},"PeriodicalIF":0.0,"publicationDate":"2024-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11361337/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142108118","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":"Novel Effective Therapeutic Regimen for Recurrent/Metastatic Head and Neck Squamous Cell Cancer: Concurrent Triple Oral Metronomic Chemotherapy and Immunotherapy.","authors":"Sewanti Limaye, Mohan Menon, Shambhavi Singh, Pritam Kataria, Aditya V Shreenivas, Rajan Datar, Darshana Patil, Prashant Kumar, Niyati Shah, Hardik Sheth, Suku Sneha, Chetan Madre, Ruturaj Deshpande, Narayan K Menon, Prasad Dandekar, Vijay Haribhakti","doi":"10.36401/JIPO-24-1","DOIUrl":"10.36401/JIPO-24-1","url":null,"abstract":"","PeriodicalId":16081,"journal":{"name":"Journal of Immunotherapy and Precision Oncology","volume":"7 3","pages":"171-177"},"PeriodicalIF":0.0,"publicationDate":"2024-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11361342/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142108117","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":"Updates in Drug-Related Pneumonitis Due to Targeted Oncologic Therapies","authors":"Kathy L. Chan, S. Faiz, Mehmet Altan, A. Sheshadri","doi":"10.36401/jipo-24-12","DOIUrl":"https://doi.org/10.36401/jipo-24-12","url":null,"abstract":"\u0000 An increasing number of newer targeted oncologic therapies approved for clinical use can cause drug-related pneumonitis. Drug-related pneumonitis can be difficult to diagnose and requires a high index of suspicion. This review serves as an update to a prior review in this journal about pneumonitis with precision oncology therapies. In this review, we focus on the incidence, timing of onset, and imaging patterns of pneumonitis associated with a number of newly approved precision oncologic agents, with a particular focus on new antibody-drug conjugate therapies.","PeriodicalId":16081,"journal":{"name":"Journal of Immunotherapy and Precision Oncology","volume":"29 25","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-08-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141924883","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Advanced Granulosa Cell Tumors of the Ovary: A Review with a Focus on Current and Novel Therapeutic Approaches.","authors":"Mohamad A Salkeni, Sarah Shin, Naoko Takebe, Sally Stevens, Alice Chen","doi":"10.36401/JIPO-23-40","DOIUrl":"https://doi.org/10.36401/JIPO-23-40","url":null,"abstract":"<p><p>Granulosa cell tumor (GCT) is the most common nonepithelial ovarian malignancy. Still, it is considered rare, with a paucity of high-level evidence guiding management, particularly in the metastatic setting. Advancements in molecular pathology allowed the identification of several targetable mutations that play an important role in GCT pathogenesis. Although current management approaches rely on guidelines extrapolated from the more common epithelial subtype, the unique histopathologic and molecular characteristics of GCTs entail a more focused approach. Systemic therapy remains the cornerstone treatment for advanced disease, and although chemotherapy has been the standard for decades, targeted treatments have gained considerable attention lately. Due to the rarity of this disease, validation of new therapies in large trials is the rate-limiting step for developing evidence-based recommendations. This review sheds light on pathogenesis, clinical and molecular characteristics, and prognostic factors, and discusses current treatment options including the role of novel therapies and immune checkpoint inhibitors in advanced GCT.</p>","PeriodicalId":16081,"journal":{"name":"Journal of Immunotherapy and Precision Oncology","volume":"7 4","pages":"263-271"},"PeriodicalIF":0.0,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11541922/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142621975","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":"Diaphragmatic Myopathy Associated with Dual Immune Checkpoint Inhibitors in a Patient with Renal Cell Carcinoma","authors":"Jeremy R. Walder, S. Faiz, S. Tummala, S. Weathers, Nicolas L. Palaskas, Maryam Buni, A. Sheshadri, L. Bashoura","doi":"10.36401/jipo-23-45","DOIUrl":"https://doi.org/10.36401/jipo-23-45","url":null,"abstract":"\u0000 Immune-related adverse events (irAEs) have become increasingly prevalent with immune checkpoint inhibitor (ICI) cancer treatment. We present a 79-year-old man with metastatic renal cell carcinoma who developed shortness of breath and hypercapnic respiratory insufficiency after his first cycle of nivolumab and ipilimumab. Laboratory data showed elevated creatinine kinase, troponins, and transaminases. Computed tomography of the chest demonstrated bilateral lower lobe atelectasis. Heart catheterization and endomyocardial biopsy were unremarkable. Electromyogram (EMG) and nerve conduction studies (NCS) of the limb muscles revealed mild diffuse myopathy, normal sensory nerve conductions, and low-amplitude motor responses. Subsequent diaphragmatic EMG and NCS demonstrated severe myopathy. ICI-mediated myopathy predominantly affecting diaphragmatic muscles was diagnosed. Treatment included intravenous methylprednisolone, infliximab, abatacept, rituximab, and plasmapheresis. He underwent tracheostomy placement on hospital day 11 due to minimal improvement. He was discharged to a long-term acute care hospital, but unfortunately, he died less than 1 month later due to recurrent infections. irAEs can affect any organ system, but diaphragmatic dysfunction is uncommon. Use of diaphragmatic EMG, NCS, ultrasound study, or biopsy can support the diagnosis. Treatment includes systemic steroids, plasmapheresis, immunosuppressive medications, respiratory support, and cessation of causative medications. ICI-related diaphragmatic dysfunction should be suspected in those patients at risk with hypoxia, hypercapnia, or prolonged invasive or noninvasive ventilation without a distinct etiology. This case report exemplifies the importance of multidisciplinary workup and management of respiratory symptoms and insufficiency to identify and ameliorate irAEs. Diaphragmatic involvement can be associated with significant morbidity and mortality despite early aggressive multimodal therapy.","PeriodicalId":16081,"journal":{"name":"Journal of Immunotherapy and Precision Oncology","volume":" 16","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141831496","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Abstracts Presented at the 2024 Win Symposium in Partnership with Burjeel Holdings: March 1–2 Abu Dhabi, United Arab Emirates","authors":"","doi":"10.36401/jipo-24-x2","DOIUrl":"https://doi.org/10.36401/jipo-24-x2","url":null,"abstract":"","PeriodicalId":16081,"journal":{"name":"Journal of Immunotherapy and Precision Oncology","volume":" 2","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-05-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141126926","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Decentralized Clinical Trials in Early Drug Development—A Framework Proposal","authors":"Diogo J. Silva, B. Nelson, J. Rodón","doi":"10.36401/jipo-23-33","DOIUrl":"https://doi.org/10.36401/jipo-23-33","url":null,"abstract":"\u0000 The COVID-19 pandemic has led to a rethinking of clinical trial design to maintain clinical research activity, with regulatory changes allowing for the wider implementation and development of decentralized design models. Evidence of the feasibility and benefits associated with a remote design comes mainly from observational studies or phase 2 and 3 clinical trials, in which implementation is easier with a better-established safety profile. Early drug development is a slow and expensive process in which accrual and safety are key aspects of success. Applying a decentralized model to phase 1 clinical trials could improve patient accrual by removing geographic barriers, improving patient population diversity, strengthening evidence for rare tumors, and reducing patients’ financial and logistical burdens. However, safety monitoring, data quality, shipment, and administration of the investigational product are challenges to its implementation. Based on published data for decentralized clinical trials, we propose an exploratory framework of solutions to enable the conceptualization of a decentralized model for phase 1 clinical trials.","PeriodicalId":16081,"journal":{"name":"Journal of Immunotherapy and Precision Oncology","volume":"51 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141003242","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}