Journal of Immunotherapy and Precision Oncology最新文献

{"title":"Evaluating Immune-Related Adverse Events Using PRO-CTCAE in a Phase II Study of Ipilimumab for Hormone-Sensitive Prostate Cancer.","authors":"Daniel Vargas P de Almeida, Justine M Anderson, Daniel C Danila, Michael J Morris, Susan F Slovin, Wassim Abida, Erica D Cohn, Raymond E Baser, Howard I Scher, Karen A Autio","doi":"10.36401/JIPO-23-9","DOIUrl":"10.36401/JIPO-23-9","url":null,"abstract":"<p><strong>Introduction: </strong> Use of the Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) during chemotherapy is associated with decreased hospitalization rates, improved quality of life, and longer survival. Limited data exist on the benefit of this symptom assessment tool for monitoring immune-related adverse events (irAEs).</p><p><strong>Methods: </strong> We incorporated irAE-related items from the National Cancer Institute's (NCI) PRO-CTCAE in a trial evaluating ipilimumab in combination with androgen deprivation therapy in 16 patients with hormone-sensitive prostate cancer. For comparison, NCI's CTCAE version 4.0 was used by clinicians.</p><p><strong>Results: </strong> IrAE-related PRO-CTCAE surveys and matched CTCAEs (184 pairs) reporting abdominal pain, diarrhea, fatigue, anorexia, nausea, vomiting, rash, and pruritus were collected at each treatment administration and during follow-up. Fatigue, diarrhea, rash, and pruritus were the symptoms most frequently reported by both patients and clinicians. Agreement was lowest for pruritus (κ = 0.10) and highest for rash (κ = 0.64). IrAEs were more commonly reported and of higher grade with PRO-CTCAE scores compared with CTCAE grades.</p><p><strong>Conclusion: </strong> PRO-CTCAEs focused on irAEs capture the patient's immunotherapy experience while complementing the clinician's toxicity assessment measures. Further study is needed to assess PRO-CTCAE's utility in identifying and managing irAEs.</p>","PeriodicalId":16081,"journal":{"name":"Journal of Immunotherapy and Precision Oncology","volume":"6 4","pages":"162-169"},"PeriodicalIF":0.0,"publicationDate":"2023-12-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10734393/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139032396","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: 2023.","authors":"","doi":"10.36401/JIPO-23-X2","DOIUrl":"https://doi.org/10.36401/JIPO-23-X2","url":null,"abstract":"","PeriodicalId":16081,"journal":{"name":"Journal of Immunotherapy and Precision Oncology","volume":"6 4","pages":"204"},"PeriodicalIF":0.0,"publicationDate":"2023-12-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10734398/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139032397","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":"Erratum to \"Sarcoidosis and Airway Disease After Immune Checkpoint Inhibitor Therapy: Case Study and Review of the Literature\" by Soto et al.","authors":"","doi":"10.36401/JIPO-23-CX1","DOIUrl":"https://doi.org/10.36401/JIPO-23-CX1","url":null,"abstract":"<p><p>[This corrects the article DOI: 10.36401/JIPO-22-30.].</p>","PeriodicalId":16081,"journal":{"name":"Journal of Immunotherapy and Precision Oncology","volume":"6 4","pages":"203"},"PeriodicalIF":0.0,"publicationDate":"2023-12-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10734396/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139032395","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 Ib/II Study of Lacnotuzumab in Combination with Spartalizumab in Patients with Advanced Malignancies","authors":"Jibran Ahmed, B. Stephen, Yali Yang, Chinenye Lynette Ejezie, Shubham Pant","doi":"10.36401/jipo-23-16","DOIUrl":"https://doi.org/10.36401/jipo-23-16","url":null,"abstract":"Blocking the colony-stimulating factor 1 (CSF-1) signal on tumor-associated macrophages can lead to an upregulation of checkpoint molecules, such as programmed cell death ligand 1 (PD-L1), thus causing resistance to this blockade. Combining spartalizumab (PDR001), a high-affinity, ligand-blocking, humanized anti–PD-1 immunoglobulin G4 antibody, with lacnotuzumab (MCS110), a high-affinity, humanized monoclonal antibody directed against human CSF-1 can potentially overcome this resistance. This was a multicenter, phase Ib/II trial using a combination of spartalizumab with lacnotuzumab in patients with advanced cancers, including anti–PD-1/PD-L1 treatment-resistant melanoma, and anti–PD-1/PD-L1 treatment-naïve triple-negative breast cancer, pancreatic cancer, and endometrial cancer (ClinicalTrials.gov identifier: NCT02807844). The primary objective of dose escalation phase Ib was to assess safety, tolerability, and recommended phase II dose. The primary objective of the phase II expansion study was to assess the combination’s antitumor activity, including objective response rate and clinical benefit rate. A total of eight patients (five in phase Ib and three in phase II) were evaluable for adverse events (AEs) at our study site. All eight patients experienced at least grade 1 AE. The most common treatment-related AEs were increased serum aspartate aminotransferase (38%), fatigue (38%), anemia (25%), increased alkaline phosphatase (25%), hyperbilirubinemia (25%), hypocalcemia (25%), and hypoalbuminemia (25%). Most of these AEs were grade 1 or 2. None of the patients experienced grade 4 AEs and no drug-related fatal AEs were reported among the eight patients treated in the study. One (13%) patient had stable disease (SD) (captured as unknown by the study sponsor because the evaluation criteria set per protocol was not met) and three (38%) patients had progressive disease. Four (50%) patients developed clinical disease progression based on investigator evaluation. One patient with pancreatic cancer achieved immune-related SD for 26 months while on the study treatments. The study completed phase Ib dose escalation and phase II. However, gating criteria for efficacy were not met for expansion beyond 80 patients in phase II and the sponsor did not continue development of the combination of spartalizumab and lacnotuzumab for oncology indications. The potential signal of activity in pancreatic cancer should be further explored.","PeriodicalId":16081,"journal":{"name":"Journal of Immunotherapy and Precision Oncology","volume":"14 36","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-11-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139240147","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":"Oral Toxicities Associated with Immune Checkpoint Inhibitors: Meta-Analyses of Clinical Trials","authors":"Akanksha Srivastava, Graciela M. Nogueras-Gonzalez, Yimin Geng, Jasdev Singh, Jeffrey N. Myers, Yisheng Li, Mark S. Chambers","doi":"10.36401/jipo-23-14","DOIUrl":"https://doi.org/10.36401/jipo-23-14","url":null,"abstract":"Introduction Immune checkpoint inhibitors (ICIs) have revolutionized cancer treatment; however, their oral toxicity profile is not well elucidated. This review aimed to investigate the prevalence of oral toxicities including xerostomia, mucositis/stomatitis, dysgeusia, dysphagia, oral/oropharyngeal pain, oral infections, angular cheilitis, osteonecrosis, osteomyelitis, and oral mucosal reactions with ICIs. Methods A review protocol was registered with PROSPERO (ID: CRD42023391674). A systematic search of ClinicalTrials.gov was conducted as of April 10, 2022. Studies were selected, assessed, and data extracted using PRISMA guidelines. Oral toxicity data were extracted from study arms using a single immunotherapy drug. Meta-analyses were conducted to summarize prevalence of oral toxicities using random-effects models. Results Of 750 screened records, 95 trials were included in the meta-analysis with published results. Time between study completion and first publication on ClinicalTrials.gov was 1 to 146 months (mean = 20.3, SD = 18.4). Weighted pooled prevalence was 5% (95% CI: 4–6%) for xerostomia, 3% (95% CI: 3–4%) for mucositis/stomatitis, 3% (95% CI: 2–3%) for dysgeusia, 2% (95% CI: 1–2%) for dysphagia, 3% (95% CI: 2–4%) for oropharyngeal/oral pain, 2% (95% CI: 1–3%) for oral candidiasis, and 2% (95% CI: 0–4%) for angular cheilitis. Subgroup differences based on ICI drugs were minimal. No trials reported lichenoid or pemphigoid mucosal reactions. Discussion Meta-analysis results revealed low prevalence of oral toxicities with ICIs; however, data reporting was limited and inconsistent. Limitations of study dataset reveal a significant need for systematic collection of oral morbidity data as well as improved consistency and compliance of reporting results on ClinicalTrials.gov.","PeriodicalId":16081,"journal":{"name":"Journal of Immunotherapy and Precision Oncology","volume":" 13","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-11-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135285577","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":"Therapeutic Role of Synthetic Lethality in <i>ARID1A</i>-Deficient Malignancies","authors":"Kyaw Z. Hein, Bettzy Stephen, Siqing Fu","doi":"10.36401/jipo-22-37","DOIUrl":"https://doi.org/10.36401/jipo-22-37","url":null,"abstract":"Abstract AT-rich interaction domain 1A (ARID1A), a mammalian switch/sucrose nonfermenting complex subunit, modulates several cellular processes by regulating chromatin accessibility. It is encoded by ARID1A, an immunosuppressive gene frequently disrupted in a many tumors, affecting the proliferation, migration, and invasion of cancer cells. Targeting molecular pathways and epigenetic regulation associated with ARID1A loss, such as inhibiting the PI3K/AKT pathway or modulating Wnt/β-catenin signaling, may help suppress tumor growth and progression. Developing epigenetic drugs like histone deacetylase or DNA methyltransferase inhibitors could restore normal chromatin structure and function in cells with ARID1A loss. As ARID1A deficiency correlates with enhanced tumor mutability, microsatellite instability, high tumor mutation burden, increased programmed death-ligand 1 expression, and T-lymphocyte infiltration, ARID1A-deficient cells can be a potential therapeutic target for immune checkpoint inhibitors that warrants further exploration. In this review, we discuss the role of ARID1A in carcinogenesis, its crosstalk with other signaling pathways, and strategies to make ARID1A-deficient cells a potential therapeutic target for patients with cancer.","PeriodicalId":16081,"journal":{"name":"Journal of Immunotherapy and Precision Oncology","volume":"32 10","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135432274","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":"How to Build a Successful Phase I Clinical Trials Unit: Lessons Based on the MD Anderson Cancer Center Experience","authors":"Razelle Kurzrock, David Hong","doi":"10.36401/jipo-23-243","DOIUrl":"https://doi.org/10.36401/jipo-23-243","url":null,"abstract":"","PeriodicalId":16081,"journal":{"name":"Journal of Immunotherapy and Precision Oncology","volume":"14 2","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135870424","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":"Treatment for Advanced Non–Small Lung Cancer (NSCLC) with Mutated <i>EGFR</i> in Low- and Middle-Income Countries (LMICs)","authors":"Andrés F. Cardona, Vaneza Ávila, Oscar Arrieta","doi":"10.36401/jipo-23-22","DOIUrl":"https://doi.org/10.36401/jipo-23-22","url":null,"abstract":"","PeriodicalId":16081,"journal":{"name":"Journal of Immunotherapy and Precision Oncology","volume":"2 ","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135870536","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":"Sustained Clinical Response to Immunotherapy Followed by BET Inhibitor in a Patient with Unresectable Sinonasal NUT Carcinoma","authors":"Harriet Herbison, Sidney Davis, David Nickless, Andrew Haydon, Malaka Ameratunga","doi":"10.36401/jipo-23-19","DOIUrl":"https://doi.org/10.36401/jipo-23-19","url":null,"abstract":"ABSTRACT NUT carcinomas (NCs) are a group of rare tumors that can occur anywhere in the body and are defined by the fusion of the nuclear protein in testis (NUTM1) resulting in increased transcription of proto-oncogenes. NCs have a poor prognosis that varies according to the site of origin with an urgent need to develop new treatment strategies. Case reports on immunotherapy in pulmonary NC have been published, and bromodomain and extraterminal (BET) inhibitors have shown activity in NC in phase I/II trials. We present the case of a 27-year-old woman with an unresectable sinonasal NC who had a sustained clinical response to both immunotherapy and BET inhibitor therapy. This is the first reported case of immunotherapy in sinonasal NC, and it highlights the different responses to a range of treatments including BET inhibitor therapy. This case supports the theory that NCs arising from different primary sites have differing prognoses.","PeriodicalId":16081,"journal":{"name":"Journal of Immunotherapy and Precision Oncology","volume":"46 8","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"136232918","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":"Proton Craniospinal Irradiation with Immunotherapy in Two Patients with Leptomeningeal Disease from Melanoma","authors":"Ugur Sener, Mason Webb, William G. Breen, Bryan J. Neth, Nadia N. Laack, David Routman, Paul D. Brown, Anita Mahajan, Kelsey Frechette, Arkadiusz Z. Dudek, Svetomir N. Markovic, Matthew S. Block, Robert R. McWilliams, Anastasios Dimou, Lisa A. Kottschade, Heather N. Montane, Sani H. Kizilbash, Jian L. Campian","doi":"10.36401/jipo-23-20","DOIUrl":"https://doi.org/10.36401/jipo-23-20","url":null,"abstract":"ABSTRACT Introduction Proton craniospinal irradiation (pCSI) is a treatment option for leptomeningeal disease (LMD), which permits whole neuroaxis treatment while minimizing toxicity. Despite this, patients inevitably experience progression. Adding systemic therapy to pCSI may improve outcomes. Methods In this single-institution retrospective case series, we present the feasibility of treatment with pCSI (30Gy, 10 fractions) and an immune checkpoint inhibitor (ICI) in two sequential patients with LMD from melanoma. Results The first patient developed LMD related to BRAF V600E-mutant melanoma after prior ICI and BRAF-targeted therapy. After pCSI with concurrent nivolumab, the addition of relatlimab, and BRAF-targeted therapy, he remained alive 7 months after LMD diagnosis despite central nervous system progression. The second patient developed LMD related to BRAF-wildtype melanoma after up-front ICI. He received pCSI with concurrent ipilimumab and nivolumab, then nivolumab maintenance. Though therapy was held for ICI hepatitis, the patient remained progression-free 5 months after LMD diagnosis. Conclusion Adding an ICI to pCSI is feasible for patients with LMD and demonstrates a tolerable toxicity profile. While prospective evaluation is ultimately warranted, pCSI with ICI may confer survival benefits, even after prior ICI.","PeriodicalId":16081,"journal":{"name":"Journal of Immunotherapy and Precision Oncology","volume":"42 3 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"136077793","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}