Current Hematologic Malignancy Reports最新文献

{"title":"Bruton Tyrosine Kinase Inhibition: an Effective Strategy to Manage Waldenström Macroglobulinemia.","authors":"Reema K Tawfiq, Jithma P Abeykoon, Prashant Kapoor","doi":"10.1007/s11899-024-00731-0","DOIUrl":"10.1007/s11899-024-00731-0","url":null,"abstract":"<p><strong>Purpose of review: </strong>The treatment of Waldenström macroglobulinemia (WM) has evolved over the past decade. With the seminal discoveries of MYD88 and CXCR warts, hypogammaglobulinemia, infections, and myelokathexis (WHIM) mutations in WM cells, our understanding of the disease biology and treatment has improved. The development of a new class of agents, Bruton tyrosine kinase inhibitors (BTKi), has substantially impacted the treatment paradigm of WM. Herein, we review the current and emerging BTKi and the evidence for their use in WM.</p><p><strong>Recent findings: </strong>Clinical trials have established the role of covalent BTKi in the treatment of WM. Their efficacy is compromised among patients who harbor CXCR4^WHIM mutation or MYD88^WT genotype. The development of BTK^C481 mutation-mediated resistance to covalent BTKi may lead to disease refractoriness. Novel, non-covalent, next-generation BTKi are emerging, and preliminary results of the early phase clinical trials show promising activity in WM, even among patients refractory to a covalent BTKi. Covalent BTK inhibitors have demonstrated meaningful outcomes in treatment-naïve (TN) and relapsed refractory (R/R) WM, particularly among those harboring the MYD88^L265P mutation. The next-generation BTKi demonstrate improved selectivity, resulting in a more favorable toxicity profile. In WM, BTKi are administered until progression or the development of intolerable toxicity. Consequently, the potential for acquired resistance, the emergence of cumulative toxicities, and treatment-related financial burden are critical challenges associated with the continuous therapy approach. By circumventing BTK C481 mutations that alter the binding site to covalent BTKi, the non-covalent BTKi serve as alternative agents in the event of acquired resistance. Head-to-head comparative trials with the conventional chemoimmunotherapies are lacking. The findings of the RAINBOW trial (NCT046152), comparing the dexamethasone, rituximab, and cyclophosphamide (DRC) regimen to the first-generation, ibrutinib are awaited, but more studies are needed to draw definitive conclusions on the comparative efficacy of chemoimmunotherapy and BTKi. Complete response is elusive with BTKi, and combination regimens to improve upon the efficacy and limit the treatment duration are also under evaluation in WM.</p>","PeriodicalId":10852,"journal":{"name":"Current Hematologic Malignancy Reports","volume":" ","pages":"120-137"},"PeriodicalIF":2.7,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140305179","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":"Update on T-Cell Lymphoma Epidemiology.","authors":"Jane J Chen, Franco Castillo Tokumori, Christina Del Guzzo, Jeanyoung Kim, Jia Ruan","doi":"10.1007/s11899-024-00727-w","DOIUrl":"10.1007/s11899-024-00727-w","url":null,"abstract":"<p><strong>Purpose of review: </strong>T-cell lymphomas (TCLs) are a group of rare subtypes of non-Hodgkin lymphoma derived from mature T-lymphocytes. Recent updates in lymphoma classification based on the cell-of-origin pathogenesis have shed new light on TCL epidemiology and outcomes. Contemporary regional consortia and international studies, including those conducted recently in Asia and South America, have provided an updated delineation of the major subtypes across various global regions.</p><p><strong>Recent findings: </strong>Peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS), remains the most common subtype globally except in Asia, where extra-nodal NK-T cell lymphoma (ENKTL) has emerged as the most prevalent. Angioimmunoblastic T-cell lymphoma (AITL) is the second most common subtype globally except in South America where its incidence falls behind adult T-cell leukemia/lymphoma (ATLL) and ENKTL. ALK-negative anaplastic large cell lymphoma (ALCL) has been recognized as the second most common subtype in some parts of South America. Studies on the newly classified breast implant-associated ALCL (BIA-ALCL) are beginning to reveal its distribution and risk factors. Deciphering the epidemiology of TCLs is a challenging endeavor due to the rarity of these entities and ongoing refinement in classification. Collaborative efforts on prospective registries based on the most current WHO classifications will help capture the true epidemiology of TCL subtypes to better focus resources for diagnostic, prognostic, and therapeutic efforts.</p>","PeriodicalId":10852,"journal":{"name":"Current Hematologic Malignancy Reports","volume":" ","pages":"93-103"},"PeriodicalIF":2.9,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140048998","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":"Management of Patients with Early Myelofibrosis: A Discussion of Best Practices.","authors":"Prithviraj Bose","doi":"10.1007/s11899-024-00729-8","DOIUrl":"10.1007/s11899-024-00729-8","url":null,"abstract":"<p><strong>Purpose of review: </strong>Summarize best practices for management of patients with early myelofibrosis (MF).</p><p><strong>Recent findings: </strong>Myelofibrosis is a progressive myeloproliferative neoplasm (MPN) that generally produces burdensome symptoms and ultimately leads to worse overall survival than that observed in healthy controls or patients with other MPNs. Several Janus kinase inhibitors and various interferon formulations are now available for treatment of MF, with ruxolitinib notable for extending overall survival in addition to improving MF signs and symptoms. The chronic nature of the disease can lead some patients to avoid immediate treatment in favor of a watch-and-wait approach. This review summarizes the patient management approach taken in my practice, providing guidance and a discussion of best practices with an emphasis on the importance and clinical benefits of active treatment in early MF. In particular, a case is made to consider treatment with ruxolitinib for patients with intermediate-1 risk disease and to minimize delay between diagnosis and treatment initiation for patients with intermediate or high-risk disease.</p>","PeriodicalId":10852,"journal":{"name":"Current Hematologic Malignancy Reports","volume":" ","pages":"111-119"},"PeriodicalIF":2.9,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11127825/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140027611","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":"Treatment of Myelodysplastic Syndromes for Older Patients: Current State of Science, Challenges, and Opportunities","authors":"Tariq Kewan, Maximillian Stahl, Jan Philipp Bewersdorf, Amer M. Zeidan","doi":"10.1007/s11899-024-00733-y","DOIUrl":"https://doi.org/10.1007/s11899-024-00733-y","url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Purpose of Review</h3><p>Myelodysplastic syndromes/neoplasms (MDS) represent a diverse group of pathologically distinct diseases with varying prognoses and risks of leukemia progression. This review aims to discuss current treatment options for elderly patients with MDS, focusing on patients ineligible for intensive chemotherapy or allogenic hematopoietic stem cell transplantation (HSCT). The challenges associated with treatment in this population and emerging therapeutic prospects are also explored.</p><h3 data-test=\"abstract-sub-heading\">Recent Findings</h3><p>Recent advancements in molecular diagnostics have enhanced risk stratification by incorporating genetic mutations, notably through the molecular International Prognostic Scoring System (IPSS-M). Lower-risk MDS (LR-MDS) treatment ranges from observation to supportive measures and erythropoiesis-stimulating agents (ESAs), with emerging therapies like luspatercept showing promise. High-risk MDS (HR-MDS) is treated with hypomethylating agents (HMAs) or allogenic HSCT, but outcomes remain poor.</p><h3 data-test=\"abstract-sub-heading\">Summary</h3><p>Elderly MDS patients, often diagnosed after 70, pose challenges in treatment decision-making. The IPSS-M aids risk stratification, guiding therapeutic choices. For LR-MDS, supportive care, ESAs, and novel agents like luspatercept are considered. Treatment of HR-MDS involves HMAs or allogenic HSCT. Emerging treatments, including oral HMAs and novel agents targeting FLT3, and IDH 1/2 mutations, show promise. Future research should refine treatment strategies for this elderly population focusing on quality-of-life improvement.</p>","PeriodicalId":10852,"journal":{"name":"Current Hematologic Malignancy Reports","volume":"75 1","pages":""},"PeriodicalIF":2.9,"publicationDate":"2024-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140630989","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":"Telomere Biology Disorder: A Focus on Gastrointestinal and Hepatic Manifestations.","authors":"Fatima Warsame, Douglas A Simonetto","doi":"10.1007/s11899-023-00723-6","DOIUrl":"10.1007/s11899-023-00723-6","url":null,"abstract":"<p><strong>Purpose of review: </strong>Telomere biology disorders (TBD) encompass several illnesses caused by underlying mutations in telomere maintenance leading to premature telomere attrition and telomere dysfunction. These disorders have unique features but share common disease manifestations including pulmonary fibrosis, cirrhosis, and bone marrow failure. The goals of this article are to provide an overview of the gastrointestinal and hepatic manifestations of TBD, focusing on their pathophysiology, clinical disease states, and current management strategies.</p><p><strong>Recent findings: </strong>Telomere shortening has been observed in patients with chronic liver disease and is associated with a higher risk of progression to cirrhosis and portal hypertension. While the directionality of the association between telomere dysfunction and senescence on liver disease is not fully understood, research in TBD may provide clarity and could lead to future therapies for this increasingly prevalent disease. While treatment options remain limited in TBD-associated liver disease, recent studies point to the safety and efficacy of liver transplantation among patients with end-stage liver disease.</p>","PeriodicalId":10852,"journal":{"name":"Current Hematologic Malignancy Reports","volume":" ","pages":"75-81"},"PeriodicalIF":2.9,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139899450","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":"How Do We Manage Chronic Lymphocytic Leukemia in India.","authors":"Parathan Karunakaran, Nidhi Jain, Deepesh P Lad","doi":"10.1007/s11899-023-00722-7","DOIUrl":"10.1007/s11899-023-00722-7","url":null,"abstract":"<p><strong>Purpose of review: </strong>Chronic lymphocytic leukemia was an ignored leukemia in India until a decade back, given its low prevalence and absence of novel drugs to treat it. Healthcare in India is heterogeneous, with variations in population, health systems, and reimbursement options. We have focused on opinions from three hemato-oncologists incorporating an opinion poll from 44 hemato-oncologists across India on the common issues in CLL to give an idea of the practice pan-India.</p><p><strong>Recent findings: </strong>More CLL patients are being diagnosed in their early stages. There is an attempt to use prognostic and predictive markers in making shared decisions for managing CLL. There is still a role for chemoimmunotherapy (CIT) in India, given limited health insurance coverage. But with the availability of inexpensive generics, the patient preference for non-CIT options like Bruton's tyrosine kinase (BTK) inhibitors is palpable. The CLL scene in India is changing rapidly. With the wide availability of economical generic small molecule inhibitors, monoclonal antibodies, and coverage by social health insurance schemes, India is poised to cater to most CLL patient needs.</p>","PeriodicalId":10852,"journal":{"name":"Current Hematologic Malignancy Reports","volume":" ","pages":"56-64"},"PeriodicalIF":2.9,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139650465","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":"Frontline Therapy of CLL-Changing Treatment Paradigms.","authors":"Catherine C Coombs","doi":"10.1007/s11899-024-00726-x","DOIUrl":"10.1007/s11899-024-00726-x","url":null,"abstract":"<p><strong>Purpose of review: </strong>The therapeutic landscape for chronic lymphocytic leukemia (CLL) has undergone a complete makeover following the introduction of highly effective targeted therapies, beginning with ibrutinib which first attained regulatory approval for CLL in 2014.</p><p><strong>Recent findings: </strong>In recent years, we have seen further refinement of therapeutic options with the development of newer-generation Bruton's tyrosine kinase inhibitors (BTKi) including acalabrutinib and zanubrutinib that improve upon the safety of ibrutinib. Additionally, venetoclax-based approaches, combined with anti-CD20 antibodies, have allowed for time-limited targeted therapeutic strategies which are particularly attractive for certain subsets of patients though have demonstrated efficacy across all subgroups. Lastly, there is an ongoing movement toward the development of time-limited strategies inclusive of both a BTKi and venetoclax that may further widen potential options. CLL patients requiring frontline therapy have a unique burden of choice between highly effective therapies that differ substantially with respect to side effect profiles and schedules. This review will focus on the frontline management of CLL in the setting of these rapidly changing options.</p>","PeriodicalId":10852,"journal":{"name":"Current Hematologic Malignancy Reports","volume":" ","pages":"65-74"},"PeriodicalIF":2.9,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139711767","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":"Treatment of Richter's Transformation with Novel Therapies.","authors":"Amneet Bajwa, Alma Habib, Adam S Kittai","doi":"10.1007/s11899-023-00721-8","DOIUrl":"10.1007/s11899-023-00721-8","url":null,"abstract":"<p><strong>Purpose of review: </strong>This review presents recently published clinical trial data and ongoing investigations regarding the treatment of Richter's transformation (RT).</p><p><strong>Recent findings: </strong>Recently, numerous approaches have been investigated for the treatment of RT including: traditional chemoimmunotherapy regimens combined with targeted agents such as BTKi and BCL2i; immunotherapy combined with targeted agents; non-covalent BTKis; bispecific T cell engagers; and CART therapy. In addition, various novel targeted agents are currently being studied for the treatment of RT in phase 1 and 2 clinical trials. Standard of care treatment with chemoimmunotherapy for RT has limited efficacy in achieving durable remissions. Here, we review recent data on the use of combination treatments and targeted agents in RT. Although some progress has been made in the investigation to optimize treatment of RT, further study is needed to evaluate long term outcomes of recently published trials and test efficacy of upcoming novel agents.</p>","PeriodicalId":10852,"journal":{"name":"Current Hematologic Malignancy Reports","volume":" ","pages":"45-55"},"PeriodicalIF":2.9,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10894755/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139402178","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":"Transplantation and Cellular Therapy for Older Adults-The MSK Approach.","authors":"Richard J Lin, Parastoo B Dahi, Beatriz Korc-Grodzicki, Armin Shahrokni, Ann A Jakubowski, Sergio A Giralt","doi":"10.1007/s11899-024-00725-y","DOIUrl":"10.1007/s11899-024-00725-y","url":null,"abstract":"<p><strong>Purpose of review: </strong>Hematologic malignances more commonly affect older individuals and often present with advanced, higher risk disease than younger patients. Allogeneic and autologous hematopoietic cell transplantation is well-established treatment modalities with curative potential following either frontline treatments for these diseases or salvage therapy in the relapsed or refractory setting. More recently, novel cellular immunotherapy such as chimeric antigen receptor T-cell therapy has been shown to lead to high response rate and durable remission in many patients with advanced blood cancers.</p><p><strong>Recent findings: </strong>Given unique characteristics of older patients, how best to deliver these higher-intensity and time sensitive treatment modalities for them remains challenging. Moreover, their short-term and potential long-term impact on their functional status, cognitive status, and quality of life may be significant considerations for many older patients. All these issues contributed to the lack of access and significant underutilization of these potential curative treatment strategies. In this review, we present up to date evidence to support potential benefits of transplantation and cellular therapy for older adults, their steady improving outcomes, and most importantly, highlight the use of geriatric assessment to help select appropriate older patients and optimize them prior to and following transplantation and cellular therapy. We specifically describe our approach at Memorial Sloan Kettering Cancer Center and encouraging early results from its implementation.</p>","PeriodicalId":10852,"journal":{"name":"Current Hematologic Malignancy Reports","volume":" ","pages":"82-91"},"PeriodicalIF":2.9,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11126330/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139706318","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":"Blinatumomab in Practice.","authors":"Jeffrey Lantz, Natalie Pham, Caroline Jones, Daniel Reed, Firas El Chaer, Michael Keng","doi":"10.1007/s11899-023-00714-7","DOIUrl":"10.1007/s11899-023-00714-7","url":null,"abstract":"<p><strong>Purpose of review: </strong>Acute lymphoblastic leukemia (ALL) is a rare hematologic neoplasm in adults, with most cases defined by pathology related to abnormal B cell proliferation known as B-cell ALL. The course is challenging, with less-than-optimal survival outcomes, even with aggressive multiagent chemotherapy and consideration for stem cell transplantation. Novel therapies focused on targetable pathways are being investigated to improve outcomes while simultaneously decreasing toxicity. In our review, we aim to evaluate the utilization of blinatumomab in B-cell ALL and provide insight on how this guides our management.</p><p><strong>Recent findings: </strong>Blinatumomab is a bispecific T-cell engager (BiTE) immunotherapy that neutralizes malignant cells by instigating CD3-positive T cells to target CD19-positive B cells. However, this therapy targets both malignant and non-malignant lymphocytes with potentially severe side effects such as cytokine release syndrome or neurotoxicity. Evidence evaluating utilization in the relapsed or refractory setting has been most supported; however, newer trials have also indicated improved survival in the frontline treatment of B-cell ALL. As this therapy is relatively new, the treatment team may include members who are less experienced with the typical treatment course and drug mechanics. This review synthesized available data investigating the effectiveness of blinatumomab effectiveness and its adverse events in addition to providing guidance on safe administration methods utilizing a multidisciplinary healthcare team. When care is coordinated in these settings, serious side effects can be recognized early, allowing for necessary intervention leading to improved quality of life and overall survival. Future research will continue to evaluate blinatumomab in different lines of therapy and expand its way into community settings.</p>","PeriodicalId":10852,"journal":{"name":"Current Hematologic Malignancy Reports","volume":" ","pages":"1-8"},"PeriodicalIF":2.9,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138498040","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}