Pub Date : 2024-12-02DOI: 10.1016/s1470-2045(24)00631-4
Mohiuddin A K Chowdhury, Tuhin Biswas, Tofrida Rahman, Omar Salma, , Heath Devin Skinner, Stephen Avery, Wilfred Ngwa, M Saiful Huq
<h2>Section snippets</h2><section><section><h2>Demographic profile</h2>As of October, 2023, the UN High Commissioner for Refugees (UNHCR) <span><span>reported</span><svg aria-label="Opens in new window" focusable="false" height="20" viewbox="0 0 8 8"><path d="M1.12949 2.1072V1H7V6.85795H5.89111V2.90281L0.784057 8L0 7.21635L5.11902 2.1072H1.12949Z"></path></svg></span> that 967 842 Rohingya refugees were living in Bangladesh. Approximately 936 961 (96%) of these refugees reside in 33 overcrowded camps (with approximately 40 000 people living per km2) in the Ukhiya and Teknaf subdistricts of Cox's Bazar, while around 30 000 have been relocated to the island of Bhasan Char as part of a resettlement initiative by the Bangladesh Government<sup>41</sup> (Figure 1, Figure 2). The Rohingya population</section></section><section><section><h2>Cancer prevention, awareness, and education</h2>Low awareness and education about cancer prevention exacerbates the health crisis, directly contributing to high-risk lifestyle behaviours in the Rohingya refugee camps. A <span><span>study</span><svg aria-label="Opens in new window" focusable="false" height="20" viewbox="0 0 8 8"><path d="M1.12949 2.1072V1H7V6.85795H5.89111V2.90281L0.784057 8L0 7.21635L5.11902 2.1072H1.12949Z"></path></svg></span> revealed that 70 (82·4%) of 85 participants were unaware of the link between smoking and lung cancer, with more than three-quarters regularly using tobacco products. The widespread use of betel nuts with burnt tobacco (jorda) further elevates the risk of oral cancer, yet in another cross-sectional <span><span>study</span><svg aria-label="Opens in new window" focusable="false" height="20" viewbox="0 0 8 8"><path d="M1.12949 2.1072V1H7V6.85795H5.89111V2.90281L0.784057 8L0 7.21635L5.11902 2.1072H1.12949Z"></path></svg></span>, 95% of the</section></section><section><section><h2>Cancer care gaps in Rohingya camps</h2>Health-care providers in the Rohingya refugee camps are becoming increasingly concerned about the rising cancer burden, particularly of hepatocellular carcinoma, oral cancer, and cervical cancer. A health-care professional at Cox's Bazar Medical College Hospital mentioned, “We see a large number of hepatocellular carcinoma patients compared to other cancers. This could be because the Rohingya population lacks vaccination and awareness about cancer risk factors.”Inadequate infrastructure,</section></section><section><section><h2>Barriers to cancer care in Rohingya camps</h2>Cancer care in Rohingya camps in Bangladesh is heavily affected by political challenges, which directly influence the availability and quality of cancer treatment. The political recognition of Rohingya refugees by both the host country and the international community determines their access to medical care, including cancer treatment. Political decisions and legislation in Bangladesh can restrict the operations of humanitarian organisations and health-care providers, limiting the availability</secti
{"title":"Cancer prevention, care, and outreach among the Rohingya refugee population in Bangladesh","authors":"Mohiuddin A K Chowdhury, Tuhin Biswas, Tofrida Rahman, Omar Salma, , Heath Devin Skinner, Stephen Avery, Wilfred Ngwa, M Saiful Huq","doi":"10.1016/s1470-2045(24)00631-4","DOIUrl":"https://doi.org/10.1016/s1470-2045(24)00631-4","url":null,"abstract":"<h2>Section snippets</h2><section><section><h2>Demographic profile</h2>As of October, 2023, the UN High Commissioner for Refugees (UNHCR) <span><span>reported</span><svg aria-label=\"Opens in new window\" focusable=\"false\" height=\"20\" viewbox=\"0 0 8 8\"><path d=\"M1.12949 2.1072V1H7V6.85795H5.89111V2.90281L0.784057 8L0 7.21635L5.11902 2.1072H1.12949Z\"></path></svg></span> that 967 842 Rohingya refugees were living in Bangladesh. Approximately 936 961 (96%) of these refugees reside in 33 overcrowded camps (with approximately 40 000 people living per km2) in the Ukhiya and Teknaf subdistricts of Cox's Bazar, while around 30 000 have been relocated to the island of Bhasan Char as part of a resettlement initiative by the Bangladesh Government<sup>41</sup> (Figure 1, Figure 2). The Rohingya population</section></section><section><section><h2>Cancer prevention, awareness, and education</h2>Low awareness and education about cancer prevention exacerbates the health crisis, directly contributing to high-risk lifestyle behaviours in the Rohingya refugee camps. A <span><span>study</span><svg aria-label=\"Opens in new window\" focusable=\"false\" height=\"20\" viewbox=\"0 0 8 8\"><path d=\"M1.12949 2.1072V1H7V6.85795H5.89111V2.90281L0.784057 8L0 7.21635L5.11902 2.1072H1.12949Z\"></path></svg></span> revealed that 70 (82·4%) of 85 participants were unaware of the link between smoking and lung cancer, with more than three-quarters regularly using tobacco products. The widespread use of betel nuts with burnt tobacco (jorda) further elevates the risk of oral cancer, yet in another cross-sectional <span><span>study</span><svg aria-label=\"Opens in new window\" focusable=\"false\" height=\"20\" viewbox=\"0 0 8 8\"><path d=\"M1.12949 2.1072V1H7V6.85795H5.89111V2.90281L0.784057 8L0 7.21635L5.11902 2.1072H1.12949Z\"></path></svg></span>, 95% of the</section></section><section><section><h2>Cancer care gaps in Rohingya camps</h2>Health-care providers in the Rohingya refugee camps are becoming increasingly concerned about the rising cancer burden, particularly of hepatocellular carcinoma, oral cancer, and cervical cancer. A health-care professional at Cox's Bazar Medical College Hospital mentioned, “We see a large number of hepatocellular carcinoma patients compared to other cancers. This could be because the Rohingya population lacks vaccination and awareness about cancer risk factors.”Inadequate infrastructure,</section></section><section><section><h2>Barriers to cancer care in Rohingya camps</h2>Cancer care in Rohingya camps in Bangladesh is heavily affected by political challenges, which directly influence the availability and quality of cancer treatment. The political recognition of Rohingya refugees by both the host country and the international community determines their access to medical care, including cancer treatment. Political decisions and legislation in Bangladesh can restrict the operations of humanitarian organisations and health-care providers, limiting the availability</secti","PeriodicalId":22865,"journal":{"name":"The Lancet Oncology","volume":"19 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-12-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142760058","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}
Pub Date : 2024-12-02DOI: 10.1016/s1470-2045(24)00348-6
Oluwatobi T Arisa, Erica L Beatson, Annieka Reno, Cindy H Chau, Rosemarie Aurigemma, Patricia S Steeg, William D Figg
The translation of basic drug discoveries from laboratories to clinical use presents substantial challenges. Factors such as insufficient funding, misdirected project focus, and inability to understand a drug's limitations or strengths contribute to the difficulty of this process. To address these issues, the National Institutes of Health (NIH) has established various resources dedicated to streamlining drug development. The NIH offers access to regularly curated databases encompassing categories like drug discovery, target discovery, genomics, proteomics, and clinical datasets. The NIH also provides access to key resources through various programmes, such as the Developmental Therapeutics Program, focusing on preclinical drug discovery and the Cancer Therapy Evaluation Program, which oversees clinical trial efforts for investigational agents. These resources might include funding opportunities, access to a network of scientific experts, and services to address gaps in scientific work. This Review explores the diverse platforms and resources available at the NIH and outlines how researchers can leverage them to expedite the drug development process.
{"title":"Navigating the oncology drug discovery and development process with programmes supported by the National Institutes of Health","authors":"Oluwatobi T Arisa, Erica L Beatson, Annieka Reno, Cindy H Chau, Rosemarie Aurigemma, Patricia S Steeg, William D Figg","doi":"10.1016/s1470-2045(24)00348-6","DOIUrl":"https://doi.org/10.1016/s1470-2045(24)00348-6","url":null,"abstract":"The translation of basic drug discoveries from laboratories to clinical use presents substantial challenges. Factors such as insufficient funding, misdirected project focus, and inability to understand a drug's limitations or strengths contribute to the difficulty of this process. To address these issues, the National Institutes of Health (NIH) has established various resources dedicated to streamlining drug development. The NIH offers access to regularly curated databases encompassing categories like drug discovery, target discovery, genomics, proteomics, and clinical datasets. The NIH also provides access to key resources through various programmes, such as the Developmental Therapeutics Program, focusing on preclinical drug discovery and the Cancer Therapy Evaluation Program, which oversees clinical trial efforts for investigational agents. These resources might include funding opportunities, access to a network of scientific experts, and services to address gaps in scientific work. This Review explores the diverse platforms and resources available at the NIH and outlines how researchers can leverage them to expedite the drug development process.","PeriodicalId":22865,"journal":{"name":"The Lancet Oncology","volume":"28 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-12-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142760040","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}
Pub Date : 2024-12-02DOI: 10.1016/s1470-2045(24)00557-6
Haydee Verduzco-Aguirre, Brooke E Wilson
No Abstract
没有抽象的
{"title":"Balancing clinical benefit and social value: challenges in HTA assessments","authors":"Haydee Verduzco-Aguirre, Brooke E Wilson","doi":"10.1016/s1470-2045(24)00557-6","DOIUrl":"https://doi.org/10.1016/s1470-2045(24)00557-6","url":null,"abstract":"No Abstract","PeriodicalId":22865,"journal":{"name":"The Lancet Oncology","volume":"19 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-12-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142759954","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}
The application of artificial intelligence methods to electronic patient records paves the way for large-scale analysis of multimodal data. Such population-wide data describing deep phenotypes composed of thousands of features are now being leveraged to create data-driven algorithms, which in turn has led to improved methods for early cancer detection and screening. Remaining challenges include establishment of infrastructures for prospective testing of such methods, ways to assess biases given the data, and gathering of sufficiently large and diverse datasets that reflect disease heterogeneities across populations. This Review provides an overview of artificial intelligence methods designed to detect cancer early, including key aspects of concern (eg, the problem of data drift—when the underlying health-care data change over time), ethical aspects, and discrepancies between access to cancer screening in high-income countries versus low-income and middle-income countries.
{"title":"Artificial intelligence-aided data mining of medical records for cancer detection and screening","authors":"Amalie Dahl Haue, Jessica Xin Hjaltelin, Peter Christoffer Holm, Davide Placido, S⊘ren Brunak","doi":"10.1016/s1470-2045(24)00277-8","DOIUrl":"https://doi.org/10.1016/s1470-2045(24)00277-8","url":null,"abstract":"The application of artificial intelligence methods to electronic patient records paves the way for large-scale analysis of multimodal data. Such population-wide data describing deep phenotypes composed of thousands of features are now being leveraged to create data-driven algorithms, which in turn has led to improved methods for early cancer detection and screening. Remaining challenges include establishment of infrastructures for prospective testing of such methods, ways to assess biases given the data, and gathering of sufficiently large and diverse datasets that reflect disease heterogeneities across populations. This Review provides an overview of artificial intelligence methods designed to detect cancer early, including key aspects of concern (eg, the problem of data drift—when the underlying health-care data change over time), ethical aspects, and discrepancies between access to cancer screening in high-income countries versus low-income and middle-income countries.","PeriodicalId":22865,"journal":{"name":"The Lancet Oncology","volume":"13 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-12-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142759985","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}
Pub Date : 2024-12-02DOI: 10.1016/s1470-2045(24)00668-5
Daniel Mellor
No Abstract
没有抽象的
{"title":"Challenging cancer through poetry","authors":"Daniel Mellor","doi":"10.1016/s1470-2045(24)00668-5","DOIUrl":"https://doi.org/10.1016/s1470-2045(24)00668-5","url":null,"abstract":"No Abstract","PeriodicalId":22865,"journal":{"name":"The Lancet Oncology","volume":"26 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-12-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142760266","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}
Pub Date : 2024-11-29DOI: 10.1016/s1470-2045(24)00685-5
Vincent J Cogliano, Emanuela Corsini, Agnès Fournier, Heather H Nelson, Consolato M Sergi, Alexandra M M Antunes, Elizabeth K Cahoon, Guosheng Chen, Talita Duarte-Salles, Eric Engels, Jingqi Fu, Dori Germolec, Reza Ghiasvand, Blánaid Hicks, Bertrand J Jean-Claude, Gopabandhu Jena, Catharina M Lerche, Xilin Li, Angela Lupattelli, Thomas P Ong, Federica Madia
No Abstract
没有抽象的
{"title":"Carcinogenicity of hydrochlorothiazide, voriconazole, and tacrolimus","authors":"Vincent J Cogliano, Emanuela Corsini, Agnès Fournier, Heather H Nelson, Consolato M Sergi, Alexandra M M Antunes, Elizabeth K Cahoon, Guosheng Chen, Talita Duarte-Salles, Eric Engels, Jingqi Fu, Dori Germolec, Reza Ghiasvand, Blánaid Hicks, Bertrand J Jean-Claude, Gopabandhu Jena, Catharina M Lerche, Xilin Li, Angela Lupattelli, Thomas P Ong, Federica Madia","doi":"10.1016/s1470-2045(24)00685-5","DOIUrl":"https://doi.org/10.1016/s1470-2045(24)00685-5","url":null,"abstract":"No Abstract","PeriodicalId":22865,"journal":{"name":"The Lancet Oncology","volume":"22 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-11-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142742578","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}
Pub Date : 2024-11-29DOI: 10.1016/s1470-2045(24)00573-4
John H Heinzerling, Kathryn F Mileham, Myra M Robinson, James T Symanowski, Raghava R Induru, Gregory M Brouse, Christopher D Corso, Roshan S Prabhu, Daniel E Haggstrom, Benjamin J Moeller, William E Bobo, Carolina E Fasola, Vipul V Thakkar, Sridhar E Pal, Jenna M Gregory, Sarah L Norek, Xhevahire J Begic, Aparna H Kesarwala, Stuart H Burri, Charles B Simone
<h3>Background</h3>Patients with locally advanced non-small-cell lung cancer (NSCLC) who undergo concurrent chemotherapy and radiotherapy often experience synergistic toxicity, and local regional control rates remain poor. We assessed the activity and safety outcomes of primary tumour stereotactic body radiotherapy (SBRT) followed by conventional chemoradiotherapy to the lymph nodes and consolidation immunotherapy in patients with unresectable locally advanced NSCLC.<h3>Methods</h3>In this multicentre, single-arm, phase 2 trial, patients aged 18 years and older were enrolled at eight regional cancer centres in North Carolina and South Carolina, USA. Patients were eligible if they had stage II–III, unresectable, locally advanced NSCLC (any histology), with peripheral or central primary tumours that were 7 cm or smaller, excluding central tumours within 2 cm of involved nodal disease, and an Eastern Cooperative Oncology Group performance status of 0–2. Patients who had previously received systemic therapy or radiotherapy were excluded. Participants received SBRT to the primary tumour (50–54 Gy in three to five fractions) followed by standard radiotherapy (planned up to 60 Gy in 30 2 Gy fractions) to the involved lymph nodes with concurrent platinum doublet chemotherapy (either paclitaxel 50 mg/m<sup>2</sup> intravenously plus carboplatin area under the curve 2 mg/mL per min every 7 days for a total of six 1-week cycles or etoposide 50 mg/m<sup>2</sup> intravenously on days 1–5 and days 29–33 plus cisplatin 50 mg/m<sup>2</sup> intravenously on days 1, 8, 29, and 36 for two cycles of 4 weeks). An amendment to the protocol (Dec 11, 2017) permitted the administration of consolidation durvalumab at the discretion of the treating investigator. An additional protocol amendment on Jan 13, 2021, directed patients without disease progression after chemoradiotherapy to receive consolidation durvalumab (10 mg/kg intravenously on day 1 and day 15 of a 4-week cycle for up to 12 cycles or 1500 mg intravenously on day 1 of a 4-week cycle for up to 12 cycles). The primary endpoint was 1-year progression-free survival (per Response Evaluation Criteria in Solid Tumours version 1.1), assessed in all participants who received at least one fraction of SBRT and had radiological follow-up data up to 1 year. A 1-year progression-free survival rate of greater than 60% was required to reject the null hypothesis and show significant improvement in 1-year progression-free survival. One-sided exact binomial tests were used to compare the primary endpoint versus the historical control 1-year progression-free survival rate used to determine the sample size. Safety was assessed in all patients who received at least one fraction of SBRT. This study is registered with <span><span>ClinicalTrials.gov</span><svg aria-label="Opens in new window" focusable="false" height="20" viewbox="0 0 8 8"><path d="M1.12949 2.1072V1H7V6.85795H5.89111V2.90281L0.784057 8L0 7.21635L5.11902 2.1072H1.1294
{"title":"Primary lung tumour stereotactic body radiotherapy followed by concurrent mediastinal chemoradiotherapy and adjuvant immunotherapy for locally advanced non-small-cell lung cancer: a multicentre, single-arm, phase 2 trial","authors":"John H Heinzerling, Kathryn F Mileham, Myra M Robinson, James T Symanowski, Raghava R Induru, Gregory M Brouse, Christopher D Corso, Roshan S Prabhu, Daniel E Haggstrom, Benjamin J Moeller, William E Bobo, Carolina E Fasola, Vipul V Thakkar, Sridhar E Pal, Jenna M Gregory, Sarah L Norek, Xhevahire J Begic, Aparna H Kesarwala, Stuart H Burri, Charles B Simone","doi":"10.1016/s1470-2045(24)00573-4","DOIUrl":"https://doi.org/10.1016/s1470-2045(24)00573-4","url":null,"abstract":"<h3>Background</h3>Patients with locally advanced non-small-cell lung cancer (NSCLC) who undergo concurrent chemotherapy and radiotherapy often experience synergistic toxicity, and local regional control rates remain poor. We assessed the activity and safety outcomes of primary tumour stereotactic body radiotherapy (SBRT) followed by conventional chemoradiotherapy to the lymph nodes and consolidation immunotherapy in patients with unresectable locally advanced NSCLC.<h3>Methods</h3>In this multicentre, single-arm, phase 2 trial, patients aged 18 years and older were enrolled at eight regional cancer centres in North Carolina and South Carolina, USA. Patients were eligible if they had stage II–III, unresectable, locally advanced NSCLC (any histology), with peripheral or central primary tumours that were 7 cm or smaller, excluding central tumours within 2 cm of involved nodal disease, and an Eastern Cooperative Oncology Group performance status of 0–2. Patients who had previously received systemic therapy or radiotherapy were excluded. Participants received SBRT to the primary tumour (50–54 Gy in three to five fractions) followed by standard radiotherapy (planned up to 60 Gy in 30 2 Gy fractions) to the involved lymph nodes with concurrent platinum doublet chemotherapy (either paclitaxel 50 mg/m<sup>2</sup> intravenously plus carboplatin area under the curve 2 mg/mL per min every 7 days for a total of six 1-week cycles or etoposide 50 mg/m<sup>2</sup> intravenously on days 1–5 and days 29–33 plus cisplatin 50 mg/m<sup>2</sup> intravenously on days 1, 8, 29, and 36 for two cycles of 4 weeks). An amendment to the protocol (Dec 11, 2017) permitted the administration of consolidation durvalumab at the discretion of the treating investigator. An additional protocol amendment on Jan 13, 2021, directed patients without disease progression after chemoradiotherapy to receive consolidation durvalumab (10 mg/kg intravenously on day 1 and day 15 of a 4-week cycle for up to 12 cycles or 1500 mg intravenously on day 1 of a 4-week cycle for up to 12 cycles). The primary endpoint was 1-year progression-free survival (per Response Evaluation Criteria in Solid Tumours version 1.1), assessed in all participants who received at least one fraction of SBRT and had radiological follow-up data up to 1 year. A 1-year progression-free survival rate of greater than 60% was required to reject the null hypothesis and show significant improvement in 1-year progression-free survival. One-sided exact binomial tests were used to compare the primary endpoint versus the historical control 1-year progression-free survival rate used to determine the sample size. Safety was assessed in all patients who received at least one fraction of SBRT. This study is registered with <span><span>ClinicalTrials.gov</span><svg aria-label=\"Opens in new window\" focusable=\"false\" height=\"20\" viewbox=\"0 0 8 8\"><path d=\"M1.12949 2.1072V1H7V6.85795H5.89111V2.90281L0.784057 8L0 7.21635L5.11902 2.1072H1.1294","PeriodicalId":22865,"journal":{"name":"The Lancet Oncology","volume":"13 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-11-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142742412","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}
Pub Date : 2024-11-29DOI: 10.1016/s1470-2045(24)00508-4
Swaminathan P Iyer, R Alejandro Sica, P Joy Ho, Anca Prica, Jasmine Zain, Francine M Foss, Boyu Hu, Amer Beitinjaneh, Wen-Kai Weng, Youn H Kim, Michael S Khodadoust, Auris O Huen, Leah M Williams, Anna Ma, Elaine Huang, Avanti Ganpule, Shashwat Deepali Nagar, Parin Sripakdeevong, Erika L Cullingford, Sushant Karnik, Steven M Horwitz
<h3>Background</h3>Effective treatment options are scarce for relapsed or refractory T-cell lymphoma. This study assesses the safety and activity of CTX130 (volamcabtagene durzigedleucel), a CD70-directed, allogeneic chimeric antigen receptor (CAR) immunotherapy manufactured from healthy donor T cells, in patients with relapsed or refractory T-cell lymphoma.<h3>Methods</h3>This single-arm, open-label, phase 1 study was done at ten medical centres across the USA, Australia, and Canada in patients (aged ≥18 years) with relapsed or refractory peripheral T-cell lymphoma or cutaneous T-cell lymphoma, who had received at least one or at least two previous systemic therapy lines, respectively, and had an Eastern Cooperative Oncology Group (ECOG) performance status of 0–1. Patients underwent lymphodepletion with fludarabine 30 mg/m<sup>2</sup> and cyclophosphamide 500 mg/m<sup>2</sup> (intravenously daily for 3 days), followed by intravenous CTX130 infusion at dose levels ranging from 3 × 10<sup>7</sup> CAR+ T cells (dose level 1) to 9 × 10<sup>8</sup> CAR+ T cells (dose level 4). The primary endpoint was the incidence of adverse events, defined as dose-limiting toxicities occurring within 28 days post-infusion. Secondary endpoints included objective response rate. Safety and activity analyses were performed on data from all patients who received CTX130. The trial is registered with <span><span>ClinicalTrials.gov</span><svg aria-label="Opens in new window" focusable="false" height="20" viewbox="0 0 8 8"><path d="M1.12949 2.1072V1H7V6.85795H5.89111V2.90281L0.784057 8L0 7.21635L5.11902 2.1072H1.12949Z"></path></svg></span> (<span><span>NCT04502446</span><svg aria-label="Opens in new window" focusable="false" height="20" viewbox="0 0 8 8"><path d="M1.12949 2.1072V1H7V6.85795H5.89111V2.90281L0.784057 8L0 7.21635L5.11902 2.1072H1.12949Z"></path></svg></span>) and EudraCT (2019-004526-25) and is closed to enrolment.<h3>Findings</h3>Between Aug 28, 2020, and May 30, 2023, 41 patients were enrolled and 39 (95%) received CTX130. The median patient follow-up was 7·4 months (IQR 3·1–12·2). 21 (54%) of 39 patients were female and 18 (46%) were male. 24 (62%) patients were White, eight (21%) were Black, three (8%) were Asian, three (8%) were from other racial or ethnic groups, and one (3%) was not reported. The median number of previous lines of anticancer therapy was 2·5 (IQR 1·3–4·0) for patients with peripheral T-cell lymphoma and 5·0 (IQR 5·0–7·0) for patients with cutaneous T-cell lymphoma. Cytokine release syndrome was the most common adverse event, occurring in 26 (67%) of 39 patients (23 were grade 1–2, two were grade 3, and one was a grade 4 dose-limiting toxicity at dose level 4). Grade 1–2 neurotoxic events were observed in four (10%) of 39 patients. The most common grade 3–4 adverse events were neutropenia (14 [36%]), anaemia (11 [28%]), and thrombocytopenia (six [15%]). Serious adverse events occurred in 25 (64%) patients, with CTX130-related serious adv
{"title":"Safety and activity of CTX130, a CD70-targeted allogeneic CRISPR-Cas9-engineered CAR T-cell therapy, in patients with relapsed or refractory T-cell malignancies (COBALT-LYM): a single-arm, open-label, phase 1, dose-escalation study","authors":"Swaminathan P Iyer, R Alejandro Sica, P Joy Ho, Anca Prica, Jasmine Zain, Francine M Foss, Boyu Hu, Amer Beitinjaneh, Wen-Kai Weng, Youn H Kim, Michael S Khodadoust, Auris O Huen, Leah M Williams, Anna Ma, Elaine Huang, Avanti Ganpule, Shashwat Deepali Nagar, Parin Sripakdeevong, Erika L Cullingford, Sushant Karnik, Steven M Horwitz","doi":"10.1016/s1470-2045(24)00508-4","DOIUrl":"https://doi.org/10.1016/s1470-2045(24)00508-4","url":null,"abstract":"<h3>Background</h3>Effective treatment options are scarce for relapsed or refractory T-cell lymphoma. This study assesses the safety and activity of CTX130 (volamcabtagene durzigedleucel), a CD70-directed, allogeneic chimeric antigen receptor (CAR) immunotherapy manufactured from healthy donor T cells, in patients with relapsed or refractory T-cell lymphoma.<h3>Methods</h3>This single-arm, open-label, phase 1 study was done at ten medical centres across the USA, Australia, and Canada in patients (aged ≥18 years) with relapsed or refractory peripheral T-cell lymphoma or cutaneous T-cell lymphoma, who had received at least one or at least two previous systemic therapy lines, respectively, and had an Eastern Cooperative Oncology Group (ECOG) performance status of 0–1. Patients underwent lymphodepletion with fludarabine 30 mg/m<sup>2</sup> and cyclophosphamide 500 mg/m<sup>2</sup> (intravenously daily for 3 days), followed by intravenous CTX130 infusion at dose levels ranging from 3 × 10<sup>7</sup> CAR+ T cells (dose level 1) to 9 × 10<sup>8</sup> CAR+ T cells (dose level 4). The primary endpoint was the incidence of adverse events, defined as dose-limiting toxicities occurring within 28 days post-infusion. Secondary endpoints included objective response rate. Safety and activity analyses were performed on data from all patients who received CTX130. The trial is registered with <span><span>ClinicalTrials.gov</span><svg aria-label=\"Opens in new window\" focusable=\"false\" height=\"20\" viewbox=\"0 0 8 8\"><path d=\"M1.12949 2.1072V1H7V6.85795H5.89111V2.90281L0.784057 8L0 7.21635L5.11902 2.1072H1.12949Z\"></path></svg></span> (<span><span>NCT04502446</span><svg aria-label=\"Opens in new window\" focusable=\"false\" height=\"20\" viewbox=\"0 0 8 8\"><path d=\"M1.12949 2.1072V1H7V6.85795H5.89111V2.90281L0.784057 8L0 7.21635L5.11902 2.1072H1.12949Z\"></path></svg></span>) and EudraCT (2019-004526-25) and is closed to enrolment.<h3>Findings</h3>Between Aug 28, 2020, and May 30, 2023, 41 patients were enrolled and 39 (95%) received CTX130. The median patient follow-up was 7·4 months (IQR 3·1–12·2). 21 (54%) of 39 patients were female and 18 (46%) were male. 24 (62%) patients were White, eight (21%) were Black, three (8%) were Asian, three (8%) were from other racial or ethnic groups, and one (3%) was not reported. The median number of previous lines of anticancer therapy was 2·5 (IQR 1·3–4·0) for patients with peripheral T-cell lymphoma and 5·0 (IQR 5·0–7·0) for patients with cutaneous T-cell lymphoma. Cytokine release syndrome was the most common adverse event, occurring in 26 (67%) of 39 patients (23 were grade 1–2, two were grade 3, and one was a grade 4 dose-limiting toxicity at dose level 4). Grade 1–2 neurotoxic events were observed in four (10%) of 39 patients. The most common grade 3–4 adverse events were neutropenia (14 [36%]), anaemia (11 [28%]), and thrombocytopenia (six [15%]). Serious adverse events occurred in 25 (64%) patients, with CTX130-related serious adv","PeriodicalId":22865,"journal":{"name":"The Lancet Oncology","volume":"72 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-11-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142742577","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}
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