Prajwal Dhakal, Mario Sy, G. Sutamtewagul, Eric Mou, Nanmeng Yu, N. Pemmaraju
Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare and clinically aggressive hematologic malignancy with limited treatment options. Currently, standard treatment strategies include clinical trials; chemotherapy regimens such as hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone (HCVAD); and tagraxofusp-erzs (TAG, previously SL-401) which is the first-in-class targeted therapy against CD123. TAG received Food and Drug Administration approval for frontline BPDCN treatment in December 2018 and has increasingly become an alternative to chemotherapy, offering potentially more effective and less toxic options. However, despite promising results, there are still patients who may be resistant to TAG monotherapy and/or who respond but eventually relapse. Herein, we discuss an important patient case of BPDCN treated with TAG and review BPDCN treatment strategies.
大疱性浆细胞树突状细胞瘤（BPDCN）是一种罕见的临床侵袭性血液系统恶性肿瘤，治疗方案有限。目前，标准的治疗策略包括临床试验；超剂量环磷酰胺、长春新碱、多柔比星和地塞米松（HCVAD）等化疗方案；以及 tagraxofusp-erzs（TAG，前身为 SL-401），它是首个针对 CD123 的同类靶向疗法。TAG于2018年12月获得美国食品和药物管理局批准用于一线BPDCN治疗，并逐渐成为化疗的替代疗法，提供了可能更有效、毒性更低的选择。然而，尽管结果令人鼓舞，但仍有患者可能对 TAG 单药治疗产生耐药性和/或有反应但最终复发。在此，我们将讨论一例使用 TAG 治疗的重要 BPDCN 患者，并回顾 BPDCN 的治疗策略。
{"title":"Overcoming Tagraxofusp-Erzs Monotherapy Resistance in Blastic Plasmacytoid Dendritic Cell Neoplasm (BPDCN) in a Real-World Clinical Setting","authors":"Prajwal Dhakal, Mario Sy, G. Sutamtewagul, Eric Mou, Nanmeng Yu, N. Pemmaraju","doi":"10.36401/jipo-23-43","DOIUrl":"https://doi.org/10.36401/jipo-23-43","url":null,"abstract":"\u0000 Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare and clinically aggressive hematologic malignancy with limited treatment options. Currently, standard treatment strategies include clinical trials; chemotherapy regimens such as hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone (HCVAD); and tagraxofusp-erzs (TAG, previously SL-401) which is the first-in-class targeted therapy against CD123. TAG received Food and Drug Administration approval for frontline BPDCN treatment in December 2018 and has increasingly become an alternative to chemotherapy, offering potentially more effective and less toxic options. However, despite promising results, there are still patients who may be resistant to TAG monotherapy and/or who respond but eventually relapse. Herein, we discuss an important patient case of BPDCN treated with TAG and review BPDCN treatment strategies.","PeriodicalId":506669,"journal":{"name":"Journal of Immunotherapy and Precision Oncology","volume":" 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140689820","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}
Abdul-Rahman Jazieh, Nihal El Rouby, Andrew Guinigundo, Karen M. Huelsman, Emily Curran, Rafiullah Khan, Jaime Grund, Alejandro R. Calvo, Jason J. Claes, Sarah C. Overton, Sally Hellard, Leah Vasiliadis, Minetta Liu, B. Blaxall
{"title":"A Systematic Approach to Optimize the Implementation of Precision Oncology in Clinical Practice: A Meeting Proceeding","authors":"Abdul-Rahman Jazieh, Nihal El Rouby, Andrew Guinigundo, Karen M. Huelsman, Emily Curran, Rafiullah Khan, Jaime Grund, Alejandro R. Calvo, Jason J. Claes, Sarah C. Overton, Sally Hellard, Leah Vasiliadis, Minetta Liu, B. Blaxall","doi":"10.36401/jipo-23-41","DOIUrl":"https://doi.org/10.36401/jipo-23-41","url":null,"abstract":"","PeriodicalId":506669,"journal":{"name":"Journal of Immunotherapy and Precision Oncology","volume":"59 11","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140748656","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}
Abdul-Rahman Jazieh, A. Bounedjar, Hikmat Abdel-Razeq, Elif Berna Koksoy, J. Ansari, A. Tfayli, E. Tashkandi, W. Jastaniah, M. Alorabi, Amira D. Darwish, A. Rabea, Ashwaq Al Olayan, F. Ibnshamsah, Hassan Errihani, M. Alkaiyat, Fazal Hussain, Khaled Alkattan, S. Bruinooge, E. Garrett-Mayer, Hani Tamim
Despite extensive studies of the impact of COVID-19 on patients with cancer, there is a dearth of information from the Middle East and North Africa (MENA) region. Our study aimed to report pertinent MENA COVID-19 and Cancer Registry (MCCR) findings on patient management and outcomes. MCCR was adapted from the American Society of Clinical Oncology COVID-19 Registry to collect data specifically from patients with cancer and SARS-CoV-2 infection from 12 centers in eight countries including Saudi Arabia, Jordan, Lebanon, Turkey, Egypt, Algeria, United Arab Emirates, and Morocco. The Registry included data on patients and disease characteristics, treatment, and patient outcomes. Logistic regression was used to assess associations with mortality. Between November 29, 2020, and June 8, 2021, data were captured on 2008 patients diagnosed with COVID-19 from the beginning of the pandemic. Median age was 56 years (16–98), 56.4% were females, and 26% were current or ex-smokers. Breast cancer (28.5%) was the leading diagnosis and 50.5% had metastatic disease. Delays of planned treatment (>14 days) occurred in 80.3% for surgery, 48.8% for radiation therapy, and 32.9% for systemic therapy. Significant reduction in the delays of all three treatment modalities occurred after June 1, 2020. All-cause mortality rates at 30 and 90 days were 17.1% and 23.4%, respectively. All-cause mortality rates at 30 days did not change significantly after June 1, 2020; however, 90-day mortality increased from 33.4% to 42.9% before and after that date (p = 0.015). Multivariable regression analysis showed the following predictors of higher 30- and 90-day mortality: age older than 70 years, having metastatic disease, disease progression, and being off chemotherapy. Patients with cancer in the MENA region experienced similar risks and outcome of COVID-19 as reported in other populations. Although there were fewer treatment delays after June 1, 2020, 90-day mortality increased, which may be attributed to other risk factors such as disease progression or new patients who presented with more advanced disease.
{"title":"Impact of COVID-19 on Management and Outcomes of Oncology Patients: Results of MENA COVID-19 and Cancer Registry (MCCR)","authors":"Abdul-Rahman Jazieh, A. Bounedjar, Hikmat Abdel-Razeq, Elif Berna Koksoy, J. Ansari, A. Tfayli, E. Tashkandi, W. Jastaniah, M. Alorabi, Amira D. Darwish, A. Rabea, Ashwaq Al Olayan, F. Ibnshamsah, Hassan Errihani, M. Alkaiyat, Fazal Hussain, Khaled Alkattan, S. Bruinooge, E. Garrett-Mayer, Hani Tamim","doi":"10.36401/jipo-23-38","DOIUrl":"https://doi.org/10.36401/jipo-23-38","url":null,"abstract":"\u0000 \u0000 \u0000 Despite extensive studies of the impact of COVID-19 on patients with cancer, there is a dearth of information from the Middle East and North Africa (MENA) region. Our study aimed to report pertinent MENA COVID-19 and Cancer Registry (MCCR) findings on patient management and outcomes.\u0000 \u0000 \u0000 \u0000 MCCR was adapted from the American Society of Clinical Oncology COVID-19 Registry to collect data specifically from patients with cancer and SARS-CoV-2 infection from 12 centers in eight countries including Saudi Arabia, Jordan, Lebanon, Turkey, Egypt, Algeria, United Arab Emirates, and Morocco. The Registry included data on patients and disease characteristics, treatment, and patient outcomes. Logistic regression was used to assess associations with mortality.\u0000 \u0000 \u0000 \u0000 Between November 29, 2020, and June 8, 2021, data were captured on 2008 patients diagnosed with COVID-19 from the beginning of the pandemic. Median age was 56 years (16–98), 56.4% were females, and 26% were current or ex-smokers. Breast cancer (28.5%) was the leading diagnosis and 50.5% had metastatic disease. Delays of planned treatment (>14 days) occurred in 80.3% for surgery, 48.8% for radiation therapy, and 32.9% for systemic therapy. Significant reduction in the delays of all three treatment modalities occurred after June 1, 2020. All-cause mortality rates at 30 and 90 days were 17.1% and 23.4%, respectively. All-cause mortality rates at 30 days did not change significantly after June 1, 2020; however, 90-day mortality increased from 33.4% to 42.9% before and after that date (p = 0.015). Multivariable regression analysis showed the following predictors of higher 30- and 90-day mortality: age older than 70 years, having metastatic disease, disease progression, and being off chemotherapy.\u0000 \u0000 \u0000 \u0000 Patients with cancer in the MENA region experienced similar risks and outcome of COVID-19 as reported in other populations. Although there were fewer treatment delays after June 1, 2020, 90-day mortality increased, which may be attributed to other risk factors such as disease progression or new patients who presented with more advanced disease.\u0000","PeriodicalId":506669,"journal":{"name":"Journal of Immunotherapy and Precision Oncology","volume":"61 ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140752330","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}
In targeted therapies and immunotherapies, the occurrence of low-grade (e.g., grade 1–2) toxicities (LGT) is common, while dose-limiting toxicities (DLT) are relatively rare. As a result, conventional phase I trial designs, solely based on DLTs and disregarding milder toxicities, are problematic when evaluating these novel therapies. Methods: To address this issue, we propose a novel phase I design called a multiple-constraint keyboard (MC-Keyboard) that integrates multiple toxicity constraints, accounting for both DLT and LGT, for precise dose escalation and de-escalation, and identification of the maximum tolerated dose (MTD). As a model-assisted design, an important feature of MC-Keyboard is that its dose-escalation or de-escalation rule can be pretabulated and incorporated into the trial protocol before the initiation of the trial, greatly simplifying its implementation. Results: The simulation study showed that the MC-Keyboard had high accuracy in identifying the MTD and is safer than some existing designs. Conclusion: The MC-Keyboard provides a novel, simple, and safe approach to assessing safety and identifying the MTD for targeted therapies and immunotherapies.
在靶向疗法和免疫疗法中，低度（如 1-2 级）毒性（LGT）很常见，而剂量限制性毒性（DLT）则相对罕见。因此，在评估这些新型疗法时，传统的 I 期试验设计仅以 DLT 为基础，而忽略了较轻的毒性，这就会产生问题。方法：为了解决这个问题，我们提出了一种名为多重约束键盘（MC-Keyboard）的新型 I 期试验设计方案，它整合了多重毒性约束，同时考虑到 DLT 和 LGT，以实现精确的剂量升级和降级，并确定最大耐受剂量（MTD）。作为一种模型辅助设计，MC-Keyboard 的一个重要特点是其剂量升级或降级规则可在试验开始前预先制成表格并纳入试验方案，从而大大简化了其实施过程。结果模拟研究表明，MC-Keyboard 在确定 MTD 方面具有很高的准确性，而且比现有的一些设计更安全。结论MC-Keyboard为评估靶向疗法和免疫疗法的安全性和确定MTD提供了一种新颖、简单、安全的方法。
{"title":"MC-Keyboard: A Practical Phase I Trial Design for Targeted Therapies and Immunotherapies Integrating Multiple-Grade Toxicities","authors":"Liyun Jiang, Zhulin Yin, Fangrong Yan, Ying Yuan","doi":"10.36401/jipo-23-35","DOIUrl":"https://doi.org/10.36401/jipo-23-35","url":null,"abstract":"\u0000 \u0000 \u0000 In targeted therapies and immunotherapies, the occurrence of low-grade (e.g., grade 1–2) toxicities (LGT) is common, while dose-limiting toxicities (DLT) are relatively rare. As a result, conventional phase I trial designs, solely based on DLTs and disregarding milder toxicities, are problematic when evaluating these novel therapies. Methods: To address this issue, we propose a novel phase I design called a multiple-constraint keyboard (MC-Keyboard) that integrates multiple toxicity constraints, accounting for both DLT and LGT, for precise dose escalation and de-escalation, and identification of the maximum tolerated dose (MTD). As a model-assisted design, an important feature of MC-Keyboard is that its dose-escalation or de-escalation rule can be pretabulated and incorporated into the trial protocol before the initiation of the trial, greatly simplifying its implementation. Results: The simulation study showed that the MC-Keyboard had high accuracy in identifying the MTD and is safer than some existing designs. Conclusion: The MC-Keyboard provides a novel, simple, and safe approach to assessing safety and identifying the MTD for targeted therapies and immunotherapies.\u0000","PeriodicalId":506669,"journal":{"name":"Journal of Immunotherapy and Precision Oncology","volume":"117 26","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140379438","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}
Despite ocular adverse events from immune checkpoint inhibitors being uncommon, they are still important complications to be aware of. We present the case of metastatic melanoma on ipilimumab/nivolumab in a patient who developed immunotherapy complications with delayed diagnosis because the only presenting symptom was unilateral ptosis. We reviewed the literature for relevant and important ocular and neurological complications of immune checkpoint inhibitors.
{"title":"Keeping an Eye Out for Immunotherapy Toxicity: A Case of Unilateral Ptosis Caused by Ipilimumab/Nivolumab Therapy","authors":"Khalid Jazieh, Lisa Kottschade, Anastasios Dimou","doi":"10.36401/jipo-23-44","DOIUrl":"https://doi.org/10.36401/jipo-23-44","url":null,"abstract":"\u0000 Despite ocular adverse events from immune checkpoint inhibitors being uncommon, they are still important complications to be aware of. We present the case of metastatic melanoma on ipilimumab/nivolumab in a patient who developed immunotherapy complications with delayed diagnosis because the only presenting symptom was unilateral ptosis. We reviewed the literature for relevant and important ocular and neurological complications of immune checkpoint inhibitors.","PeriodicalId":506669,"journal":{"name":"Journal of Immunotherapy and Precision Oncology","volume":"34 10","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140084565","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 2023 Emirates Oncology ConferenceNovember 17-19, 2023, Abu Dhabi, United Arab Emirates","authors":"","doi":"10.36401/jipo-24-x1","DOIUrl":"https://doi.org/10.36401/jipo-24-x1","url":null,"abstract":"","PeriodicalId":506669,"journal":{"name":"Journal of Immunotherapy and Precision Oncology","volume":" 66","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-02-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139793209","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 2023 Emirates Oncology ConferenceNovember 17-19, 2023, Abu Dhabi, United Arab Emirates","authors":"","doi":"10.36401/jipo-24-x1","DOIUrl":"https://doi.org/10.36401/jipo-24-x1","url":null,"abstract":"","PeriodicalId":506669,"journal":{"name":"Journal of Immunotherapy and Precision Oncology","volume":"117 5","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-02-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139852829","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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