Jennifer S. Woo , Kim Nguyen , Lawrence Liu , Amrita Krishnan , Tanya Siddiqi , Azra Borogovac
{"title":"Mobilizing CARs: Benefits, drawbacks, and directions for outpatient CAR T-cell therapy","authors":"Jennifer S. Woo , Kim Nguyen , Lawrence Liu , Amrita Krishnan , Tanya Siddiqi , Azra Borogovac","doi":"10.1053/j.seminhematol.2024.08.003","DOIUrl":"10.1053/j.seminhematol.2024.08.003","url":null,"abstract":"<div><div>Chimeric antigen receptor T-cell (CAR-T) therapy has heralded a new era in the treatment of various hematological malignancies, increasingly being utilized in earlier lines of therapy. Moreover, cellular therapies are currently under investigation for their potential in treating solid malignancies and autoimmune disorders. As the scope of indications for CAR-T therapy continues to expand, along with the associated reductions in costs and hospital admissions, many medical centers are transitioning towards outpatient CAR-T models. Moreover, ongoing efforts to mitigate complications such as cytokine release syndrome (CRS) or neurotoxicity include the development of premedication strategies, prompt management of adverse events, and the advancement of newer, safer CAR-T cell therapies. However, despite these advancements, the inherent risk of these life-threatening complications remains a critical concern in CAR-T therapy. Institutions must diligently anticipate and effectively manage these complications to ensure the safety and well-being of patients undergoing CAR-T therapy. This includes establishing robust protocols for timely identification and intervention of adverse events, and seamless pathways for transitioning patients to a higher level of care if necessary. This review provides an overview of the current landscape of outpatient CAR-T therapy and offers essential insights into the key clinical and operational considerations needed to implement a successful outpatient CAR-T program.</div></div>","PeriodicalId":21684,"journal":{"name":"Seminars in hematology","volume":"61 5","pages":"Pages 273-283"},"PeriodicalIF":5.0,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142353083","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Fast and furious: Changing gears on the road to cure with chimeric antigen receptor T cells in multiple myeloma","authors":"Nico Gagelmann , Maximilian Merz","doi":"10.1053/j.seminhematol.2024.07.002","DOIUrl":"10.1053/j.seminhematol.2024.07.002","url":null,"abstract":"<div><div>Based on the pivotal KarMMa-1 and CARTITUDE-1 studies, Idecabtagene vicleucel (Ide-cel) and Ciltacabtagene autoleucel (Cilta-cel) have been approved to treat multiple myeloma patients, who have been exposed to at least 1 proteasome inhibitor, immunomodulatory drug and anti-CD38 antibody after 4 or 3 lines of therapy, respectively. The unprecedented rates of deep and long-lasting remissions have been meanwhile confirmed in multiple real-world analyses and more recently, the KarMMa-3 and CARTITUDE-4 studies lead to the approval in earlier lines of therapy. It is currently believed that ultimately all patients with relapsed/refractory multiple myeloma experience relapse after anti-BCMA CAR T-cell therapies. There is a plethora of CAR T-cell therapies targeting novel antigens, with the aim to overcome current CAR T-cell resistance. In this review, we will summarize current evidence of novel antigens and their clinical potential. Together with current CAR T-cell therapy and T-cell engagers, these approaches might lead us to the next frontier in multiple myeloma: total immunotherapy and the road to chemotherapy-free cure.</div></div>","PeriodicalId":21684,"journal":{"name":"Seminars in hematology","volume":"61 5","pages":"Pages 306-313"},"PeriodicalIF":5.0,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141696986","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"The pediatric approach to Hodgkin lymphoma","authors":"","doi":"10.1053/j.seminhematol.2024.05.003","DOIUrl":"10.1053/j.seminhematol.2024.05.003","url":null,"abstract":"<div><p><span>Hodgkin lymphoma (HL) occurs throughout the lifespan but is one of the most common </span>cancers in adolescents<span><span> and young adults (AYA; 15-39 years). HL has become a highly curable disease with survival rates surpassing 90%, including patients with high-risk and advanced stage disease. Unfortunately, intensive treatment carries a risk of short- and long-term toxicity. Given the decades pediatric HL survivors are expected to live after treatment, the pediatric approach to treatment has focused on improving the </span>therapeutic index<span> through response adapted treatment and more recently the incorporation of novel agents. The efforts of pediatric and medical oncologists in research and clinical trial<span> development have long occurred in parallel, but recent efforts have laid the foundation for collaboration with the goal of standardizing AYA care and allowing earlier incorporation of novel therapy for younger patients. This review focuses on the evolution of the management of pediatric HL including epidemiology, biology, and approaches to upfront and salvage treatment regimens.</span></span></span></p></div>","PeriodicalId":21684,"journal":{"name":"Seminars in hematology","volume":"61 4","pages":"Pages 245-252"},"PeriodicalIF":5.0,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141055924","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Molecular biomarkers in classic Hodgkin lymphoma","authors":"","doi":"10.1053/j.seminhematol.2024.05.005","DOIUrl":"10.1053/j.seminhematol.2024.05.005","url":null,"abstract":"<div><p><span><span>Classic Hodgkin lymphoma<span> is a unique B-cell derived malignancy<span> featuring rare malignant Hodgkin and Reed Sternberg (HRS) cells that are embedded in a quantitively dominant tumor microenvironment (TME). Treatment of classic Hodgkin lymphoma has significantly evolved in the past decade with improving treatment outcomes for newly diagnosed patients and the minority of patients suffering from </span></span></span>disease progression<span><span>. However, the burden of toxicity and treatment-related long-term sequelae remains high in a typically young patient population. This highlights the need for better molecular biomarkers aiding in risk-adapted treatment strategies and predicting response to an increasing number of available treatments that now prominently involve multiple </span>immunotherapy<span> options. Here, we review modern molecular biomarker approaches that reflect both the biology of the malignant HRS cells and cellular components in the TME, while holding the promise to improve diagnostic frameworks for clinical decision-making and be feasible in clinical trials and routine practice. In particular, technical advances in sequencing and analytic pipelines using </span></span></span>liquid biopsies, as well as deep phenotypic characterization of tissue architecture at single-cell resolution, have emerged as the new frontier of biomarker development awaiting further validation and implementation in routine diagnostic procedures.</p></div>","PeriodicalId":21684,"journal":{"name":"Seminars in hematology","volume":"61 4","pages":"Pages 221-228"},"PeriodicalIF":5.0,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141538549","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"The role of autologous stem-cell transplantation in classical Hodgkin lymphoma in the modern era","authors":"Gaurav Varma , Catherine Diefenbach","doi":"10.1053/j.seminhematol.2024.06.003","DOIUrl":"10.1053/j.seminhematol.2024.06.003","url":null,"abstract":"<div><p><span><span><span>Despite excellent cure rates with modern front-line regimens, up to 20% of patients with Hodgkin lymphoma will progress through front-line therapy or experience disease relapse. Worldwide, salvage chemotherapy followed by high-dose chemotherapy with </span>autologous stem cell transplantation<span> (HDT/ASCT) is considered the standard of care for these patients and can cure approximately 50% of relapsed or refractory (R/R) patients in the second line. Brentuximab vedotin (BV), an anti-CD30 </span></span>antibody drug conjugate, and PD1 inhibitors like </span>nivolumab<span> and pembrolizumab<span><span><span>, have high response rates in patients who recur after HDT/ASCT. When used prior to HDT/ASCT, BV and PD1 inhibitors appear to dramatically increase the effectiveness of salvage therapies with complete response rates often double those seen with historic chemotherapy-based regimens and durable </span>progression free survival (PFS) post-HDT/ASCT. Emerging data in adults and from </span>pediatric trials showing a durable PFS in a subset of relapsed patients raises the question of whether HDT/ASCT is essential for cure in R/R patients after PD1 based salvage. Future studies will help clarify if ASCT can omitted PD1 based salvage to avoid the potential toxicity of HDT/ASCT without compromising cure.</span></span></p></div>","PeriodicalId":21684,"journal":{"name":"Seminars in hematology","volume":"61 4","pages":"Pages 253-262"},"PeriodicalIF":5.0,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141749003","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"The role of response adapted therapy in the era of novel agents","authors":"","doi":"10.1053/j.seminhematol.2024.06.002","DOIUrl":"10.1053/j.seminhematol.2024.06.002","url":null,"abstract":"<div><p><span><span>The optimal treatment of classic Hodgkin Lymphoma (cHL) requires an individualized approach, with therapy guided by pretreatment clinical </span>risk stratification<span> and interim response assessment with positron emission tomography (PET). The overall goal is to achieve high cure rates while minimizing </span></span>acute toxicity<span><span> and late therapy-related effects. Interim PET-adapted strategies (iPET) were initially developed with traditional chemotherapy, reducing intensity after interim complete response and escalating treatment for patients with iPET+ disease. Recently, novel agents including brentuximab vedotin and the checkpoint inhibitor </span>immunotherapies<span><span> (CPIs) pembrolizumab and </span>nivolumab<span> have been adopted into the front-line treatment of cHL, and PET-adapted approaches may be relevant for these drugs as well. In this review we discuss response-adapted strategies utilizing novel agents, consider challenges including indeterminate radiographic findings with CPIs, and address emerging techniques for response assessment including new PET-based imaging metrics and the role of circulating tumor DNA.</span></span></span></p></div>","PeriodicalId":21684,"journal":{"name":"Seminars in hematology","volume":"61 4","pages":"Pages 229-235"},"PeriodicalIF":5.0,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141414785","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"outside front cover, PMS 8883 metallic AND 4/C","authors":"","doi":"10.1053/S0037-1963(24)00093-3","DOIUrl":"10.1053/S0037-1963(24)00093-3","url":null,"abstract":"","PeriodicalId":21684,"journal":{"name":"Seminars in hematology","volume":"61 4","pages":"Page CO1"},"PeriodicalIF":5.0,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142274736","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Challenges for HL in the modern era: Questions to move the field forward","authors":"Catherine Diefenbach MD","doi":"10.1053/j.seminhematol.2024.09.002","DOIUrl":"10.1053/j.seminhematol.2024.09.002","url":null,"abstract":"","PeriodicalId":21684,"journal":{"name":"Seminars in hematology","volume":"61 4","pages":"Pages 209-211"},"PeriodicalIF":5.0,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142274737","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"The biology of classical Hodgkin lymphoma","authors":"","doi":"10.1053/j.seminhematol.2024.05.001","DOIUrl":"10.1053/j.seminhematol.2024.05.001","url":null,"abstract":"<div><p><span><span>Classical Hodgkin lymphoma (cHL) is distinguished by several important biological characteristics. The presence of Hodgkin Reed Sternberg (HRS) cells is a defining feature of this disease. The </span>tumor microenvironment with relatively few HRS cells in an expansive infiltrate of </span>immune cells<span><span> is another key feature. Numerous cell-cell mediated interactions and a plethora of cytokines in the tumor microenvironment collectively work to promote HRS cell growth and survival. Aberrancy and constitutive activation of core </span>signal transduction pathways are a hallmark trait of cHL. Genetic lesions contribute to these dysregulated pathways and evasion of the immune system through a variety of mechanisms is another notable feature of cHL. While substantial elucidation of the biology of cHL has enabled advancements in therapy, increased understanding in the future of additional mechanisms driving cHL may lead to new treatment opportunities.</span></p></div>","PeriodicalId":21684,"journal":{"name":"Seminars in hematology","volume":"61 4","pages":"Pages 212-220"},"PeriodicalIF":5.0,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141041782","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"The Management of older patients with Hodgkin lymphoma: implications of S1826","authors":"","doi":"10.1053/j.seminhematol.2024.05.004","DOIUrl":"10.1053/j.seminhematol.2024.05.004","url":null,"abstract":"<div><p>Classical Hodgkin lymphoma (cHL) is diagnosed in patients ages 60 and older in approximately 20%–25% of cases in Western populations. Outcomes in this subset of patients have historically been poor, with 5-year progression free survival (PFS) and overall survival rates significantly lower than those seen in younger patients. Challenges to overcome include age-related co-morbidities, and prominent and potentially lethal treatment-related toxicity. There have been increased efforts to study the older cHL patient population, including analysis of geriatric assessments and the integration of newer targeted therapies such as brentuximab vedotin (BV) and nivolumab (N) into treatment paradigms. A recent phase 3 clinical trial (S1826, NCT03907488) led by the North American oncology cooperative groups compared brentuximab vedotin, doxorubicin, vinblastine, and dacarbazine (BV-AVD) with nivolumab, doxorubicin, vinblastine, and dacarbazine (N-AVD). At a median follow-up of 1-year, N-AVD improved PFS vs BV-AVD in patients and few immune adverse events were observed. Moreover, in a pre-planned subset analyses of cHL patients ages ≥60 years, the 1-year PFS for N-AVD was 93% (95% CI, 79%-98%) versus 64% (95% CI, 45%-77%) for BV-AVD. In addition, N-AVD was largely better tolerated particularly in older patients, which included markedly less neuropathy, lower treatment discontinuation, and less nonrelapse mortality. As a result, N-AVD is poised to become a standard of care for older, advanced-stage cHL patients who are fit for full-dose anthracycline-based combination therapy. More studies are needed to continue to improve outcomes for older cHL patients, especially unfit and frail populations.</p></div>","PeriodicalId":21684,"journal":{"name":"Seminars in hematology","volume":"61 4","pages":"Pages 236-244"},"PeriodicalIF":5.0,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0037196324000684/pdfft?md5=e89ef70dc2ccf7bbc437d3e3abd75b4a&pid=1-s2.0-S0037196324000684-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141404293","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}