Clinical Lymphoma, Myeloma & Leukemia最新文献

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SOHO State of the Art Updates and Next Questions | CAR T Cells in T Cell Acute Lymphoblastic Leukemia and Lymphoblastic Lymphoma CAR T 细胞在 T 细胞急性淋巴细胞白血病和淋巴细胞淋巴瘤中的应用。
IF 2.7 4区 医学
Clinical Lymphoma, Myeloma & Leukemia Pub Date : 2025-02-01 DOI: 10.1016/j.clml.2024.05.018
Daniil Shmidt , Maksim Mamonkin
{"title":"SOHO State of the Art Updates and Next Questions | CAR T Cells in T Cell Acute Lymphoblastic Leukemia and Lymphoblastic Lymphoma","authors":"Daniil Shmidt ,&nbsp;Maksim Mamonkin","doi":"10.1016/j.clml.2024.05.018","DOIUrl":"10.1016/j.clml.2024.05.018","url":null,"abstract":"<div><div>Chimeric antigen receptor (CAR T) therapy produced excellent activity in patients with relapsed/refractory B-lineage malignancies. However, extending these therapies to T cell cancers requires overcoming unique challenges. In the recent years, multiple approaches have been developed in preclinical models and some were tested in clinical trials in patients with treatment-refractory T-cell malignanices with promising early results. Here, we review main hurdles impeding the success of CAR T therapy in T-cell acute lymphoblastic leukemia/lymphoma (T-ALL/LBL), discuss potential solutions, and summarize recent progress in both preclinical and clinical development of CAR T therapy for these diseases.</div></div>","PeriodicalId":10348,"journal":{"name":"Clinical Lymphoma, Myeloma & Leukemia","volume":"25 2","pages":"Pages 77-88"},"PeriodicalIF":2.7,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141491131","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
The Evolving Role of Checkpoint Inhibitors in Multiple Myeloma 检查点抑制剂在多发性骨髓瘤中不断演变的作用。
IF 2.7 4区 医学
Clinical Lymphoma, Myeloma & Leukemia Pub Date : 2025-02-01 DOI: 10.1016/j.clml.2024.08.004
Ritu Chakrabarti , David Siegel , Noa Biran
{"title":"The Evolving Role of Checkpoint Inhibitors in Multiple Myeloma","authors":"Ritu Chakrabarti ,&nbsp;David Siegel ,&nbsp;Noa Biran","doi":"10.1016/j.clml.2024.08.004","DOIUrl":"10.1016/j.clml.2024.08.004","url":null,"abstract":"<div><div>Multiple myeloma (MM) is a plasma cell dyscrasia characterized by production of abnormal levels of a monoclonal immunoglobulin or plasma cell deposition that leads to end organ destruction. The disease remains incurable despite advances in combination treatments with classes of medications that include proteosome inhibitors, immunomodulating agents, monoclonal antibodies, small molecule inhibitors, alkylating agents, T-cell-based immunotherapies, and others. Checkpoint inhibitors (CKP-I), though showing robust efficacy in solid tumor and lymphoma, have had limited success as single agents in the treatment of MM. Furthermore, early FDA holds on trials involving CKP-I in myeloma led to diminished enrollment and data on its potential use. Nevertheless, clearer understanding of the mechanisms of immune dysregulation and unique bone marrow biology in the pathophysiology of MM have opened the opportunity for future uses of CKP-I in multiple myeloma. Herein we provide a comprehensive review of the immunologic basis of multiple myeloma, preclinical and published data from trials utilizing CKP-I in MM patients, and future targets in CKP-I development that may provide promising opportunities in the treatment of MM.</div></div>","PeriodicalId":10348,"journal":{"name":"Clinical Lymphoma, Myeloma & Leukemia","volume":"25 2","pages":"Pages 96-108"},"PeriodicalIF":2.7,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142211680","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Real-Life Management of Patients Aged 80 Years Old and Over With Multiple Myeloma: Results of the EMMY Cohort 80 岁及以上多发性骨髓瘤患者的实际管理:EMMY队列的结果。
IF 2.7 4区 医学
Clinical Lymphoma, Myeloma & Leukemia Pub Date : 2025-02-01 DOI: 10.1016/j.clml.2024.09.006
T. Chalopin , M. Macro , O. Decaux , B. Royer , R. Gounot , A. Bobin , L. Karlin , M. Mohty , L. Frenzel , A. Perrot , S. Manier , L. Vincent , M. Dib , B. Slama , V. Richez , O. Allangba , P. Zunic , M. Newinger-Porte , C. Mariette , B. Joly , C. Hulin
{"title":"Real-Life Management of Patients Aged 80 Years Old and Over With Multiple Myeloma: Results of the EMMY Cohort","authors":"T. Chalopin ,&nbsp;M. Macro ,&nbsp;O. Decaux ,&nbsp;B. Royer ,&nbsp;R. Gounot ,&nbsp;A. Bobin ,&nbsp;L. Karlin ,&nbsp;M. Mohty ,&nbsp;L. Frenzel ,&nbsp;A. Perrot ,&nbsp;S. Manier ,&nbsp;L. Vincent ,&nbsp;M. Dib ,&nbsp;B. Slama ,&nbsp;V. Richez ,&nbsp;O. Allangba ,&nbsp;P. Zunic ,&nbsp;M. Newinger-Porte ,&nbsp;C. Mariette ,&nbsp;B. Joly ,&nbsp;C. Hulin","doi":"10.1016/j.clml.2024.09.006","DOIUrl":"10.1016/j.clml.2024.09.006","url":null,"abstract":"<div><h3>Introduction</h3><div>Multiple myeloma patients aged 80 years and older are a population more prone to comorbidities and frailty. We aim to describe the real-life management and outcomes of this population. EMMY is a descriptive large-scale study.</div></div><div><h3>Patients</h3><div>Between 2017 and 2021 we included 4383 patients of which 894 (20.3%) were aged ≥ 80 years. Four cohorts of patients aged ≥ 80 years were analysed: line 1 (L1), line 2 (L2), line 3 (L3) or line 4+ (L4+).</div></div><div><h3>Results</h3><div>The proportion of patients ≥ 80 years old was 20.8% in L1, 21.3% in L2, 20.9% in L3 and 17.8% in L4+. L1 patients received more treatment including a proteasome inhibitor (PI) (42.9%), L2 patients received mainly an immunomodulator (IMID) (65.9%) or an anti-CD38 (31.5%). For L3, IMID was used in 71.4% than an anti-CD38 (33.5%). L4+ patients received a PI (40.6%), IMID (33.2%) or an anti-CD38 (29.1%). Regarding efficacy, the median progression-free survival was 18.4 months in L1, 15.1 months in L2, 10.4 months in L3 and 6.5 months in L4+. The median overall survival was 49 months in L1, 31.3 months in L2, 21.4 months in L3 and 13.6 months in L4+.</div></div><div><h3>Conclusion</h3><div>EMMY cohort confirmed that patients ≥ 80 years of age represent an important proportion of MM patients, in the de novo or relapse setting. This study is an important step in improving our comprehension and management of treatment in elderly patients.</div></div>","PeriodicalId":10348,"journal":{"name":"Clinical Lymphoma, Myeloma & Leukemia","volume":"25 2","pages":"Pages e103-e109.e1"},"PeriodicalIF":2.7,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142496280","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Impact of Gut Microbiota on Lymphoma: New Frontiers in Cancer Research 肠道微生物群对淋巴瘤的影响:癌症研究的新前沿
IF 2.7 4区 医学
Clinical Lymphoma, Myeloma & Leukemia Pub Date : 2025-02-01 DOI: 10.1016/j.clml.2024.08.008
Sabri Saeed Sanabani
{"title":"Impact of Gut Microbiota on Lymphoma: New Frontiers in Cancer Research","authors":"Sabri Saeed Sanabani","doi":"10.1016/j.clml.2024.08.008","DOIUrl":"10.1016/j.clml.2024.08.008","url":null,"abstract":"<div><div>The gut microbiome (GMB), which is made up of various microorganisms, plays a crucial role in maintaining the health of the host. Disruptions in this delicate ecosystem, known as microbial dysbiosis, have been linked to various diseases, including hematologic malignancies such as lymphoma. This review article explores the complex relationship between the GMB and the development of lymphoma and highlights its implications for diagnostic and therapeutic approaches. It discusses how GMB influences lymphoma development directly through the presence of certain microorganisms and indirectly through changes in the immune system. The clinical relevance of GMB is highlighted and its potential utility for diagnosis, predicting treatment outcomes and developing personalized therapeutic strategies for lymphoma patients is demonstrated. The review also looks at microbiome-targeted interventions such as fecal microbiome transplantation and dietary modification, which have shown promise for treating microbial dysbiosis and improving patient outcomes. In addition, it highlights the analytical challenges and the need for further research to fully elucidate the mechanistic functions of the GMB in the context of lymphoma. This review emphasizes the critical role of GMB in lymphomagenesis and its potential for the development of diagnostic and therapeutic strategies.</div></div>","PeriodicalId":10348,"journal":{"name":"Clinical Lymphoma, Myeloma & Leukemia","volume":"25 2","pages":"Pages e82-e89"},"PeriodicalIF":2.7,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142281223","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
A Real-World Evaluation of Frontline Treatment for Acute Myeloid Leukemia With Azacitidine Plus Venetoclax 阿扎胞苷联合Venetoclax一线治疗急性髓系白血病的现实世界评价。
IF 2.7 4区 医学
Clinical Lymphoma, Myeloma & Leukemia Pub Date : 2025-02-01 DOI: 10.1016/j.clml.2025.01.024
Joseph Brandwein, David Page, Elena Liew, Mark Hnatiuk, Lauren Bolster, Marlene Hamilton, Daniel Sawler, Peng Wang
{"title":"A Real-World Evaluation of Frontline Treatment for Acute Myeloid Leukemia With Azacitidine Plus Venetoclax","authors":"Joseph Brandwein,&nbsp;David Page,&nbsp;Elena Liew,&nbsp;Mark Hnatiuk,&nbsp;Lauren Bolster,&nbsp;Marlene Hamilton,&nbsp;Daniel Sawler,&nbsp;Peng Wang","doi":"10.1016/j.clml.2025.01.024","DOIUrl":"10.1016/j.clml.2025.01.024","url":null,"abstract":"<div><h3>Background</h3><div>The combination of venetoclax + azacitidine (VenAza) has become the standard frontline treatment for older unfit AML patients.</div></div><div><h3>Methods</h3><div>We analyzed outcomes using VenAza for previously untreated unfit AML patients at a single center between 2020-2024.</div></div><div><h3>Results</h3><div>The overall response rate (ORR) was 69/105 (66%), was highest for patients with NPM1 (78%) and IDH1/2 (82%) mutations and lowest with TP53 mutations (40%). The median overall survival (OS) was 9.6 months, and 16.3 months for those achieving CR/CRi. There was no significant difference in OS between those achieving CR and CRi (<em>p</em> = 0.077). Patients treated between 2022-24 had a lower early death rate (8% vs. 22%) and better OS (median 10.4 vs 5.8 mos, <em>p</em> = 0.033) than those treated between 2020-21. There was no difference in OS between by age grouping or for patients with prior hypomethylating agent exposure. Patients with FLT3-ITD/RAS or TP53 mutations had an inferior OS compared with the other patients (median OS 8.1, 1.7 and 16 months, respectively). On multivariate analysis, achievement of CR/CRi was associated with better OS (<em>p</em> &lt; 0.001), and FLT3-ITS/RAS/TP53 mutations were associated with inferior OS (<em>p</em> = 0.003), while ELN2022 risk group was not associated with OS. The median DFS for patients achieving CR/CRi was 7.1, 4.9 and 21 mos, for those with FLT3-ITD/RAS, TP53 and others, respectively (<em>p</em> = 0.003).</div></div><div><h3>Conclusions</h3><div>This real-world analysis confirmed the prognostic importance of the mutational risk classification with VenAza treatment. OS was inferior to that reported in the VIALE A study but did improve over time.</div></div>","PeriodicalId":10348,"journal":{"name":"Clinical Lymphoma, Myeloma & Leukemia","volume":"25 7","pages":"Pages e435-e442"},"PeriodicalIF":2.7,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143536701","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Enhancing Multiple Myeloma Care: Implementation of Pharmacist-Led Prescribing of Immunomodulatory Drugs in an Academic Medical Setting 加强多发性骨髓瘤护理:在学术医疗机构实施药剂师开具免疫调节药物处方。
IF 2.7 4区 医学
Clinical Lymphoma, Myeloma & Leukemia Pub Date : 2025-01-29 DOI: 10.1016/j.clml.2025.01.013
Amy Indorf , Mary Kwok , Mark Jao , Ashley Chen , Grace T. Baek , Rahul Banerjee , Kara I. Cicero , Andrew J. Cowan , Andrew J. Portuguese , Linda Yoon , Eve M. Segal
{"title":"Enhancing Multiple Myeloma Care: Implementation of Pharmacist-Led Prescribing of Immunomodulatory Drugs in an Academic Medical Setting","authors":"Amy Indorf ,&nbsp;Mary Kwok ,&nbsp;Mark Jao ,&nbsp;Ashley Chen ,&nbsp;Grace T. Baek ,&nbsp;Rahul Banerjee ,&nbsp;Kara I. Cicero ,&nbsp;Andrew J. Cowan ,&nbsp;Andrew J. Portuguese ,&nbsp;Linda Yoon ,&nbsp;Eve M. Segal","doi":"10.1016/j.clml.2025.01.013","DOIUrl":"10.1016/j.clml.2025.01.013","url":null,"abstract":"<div><h3>Background</h3><div>The oncology healthcare landscape has transformed and has demonstrated the need for efficient care delivery models due to improved survival resulting in larger patient panels. Pharmacists can prescribe oral anticancer agents (OAA), laboratory orders, and supportive care treatments as licensed independent practitioners (LIP) under their pharmacist license. Using immunomodulators (IMiDs) for patients with multiple myeloma (MM) has complexities with regulatory requirements for prescribing. At our institution, the care team was spending about 240 hours per month satisfying regulatory activities. We aim to characterize the effectiveness of pharmacist LIPs for patients with MM receiving IMiD treatment.</div></div><div><h3>Methods</h3><div>A multidisciplinary quality improvement team implemented a model for OAA management with pharmacist LIPs. Patients were evaluated for IMiD adherence. Medication possession ratios (MPR) were collected using fill history for patients with 6 months of fill history pre and postpharmacist LIPs involvement, and paired McNemar's Test assessed differences in adherence. A care team survey gauged satisfaction.</div></div><div><h3>Results</h3><div>The pharmacist patient panel comprised 246 patients. There were similar adherence rates, with an MPR of 96% preintervention and 96.55% postintervention. All survey participants recommended the pharmacist prescriber for IMiDs and reported positive reviews of pharmacist involvement.</div></div><div><h3>Conclusion</h3><div>Management of OAAs by pharmacist LIPs is viable clinical model. The care team reduced their administrative burden while empowering pharmacists to practice at the top of their license. This framework serves as a guide for institutions to adapt and optimize OAA management in an increasingly complex therapeutic landscape.</div></div>","PeriodicalId":10348,"journal":{"name":"Clinical Lymphoma, Myeloma & Leukemia","volume":"25 6","pages":"Pages e424-e434"},"PeriodicalIF":2.7,"publicationDate":"2025-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143522695","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Role of Pulmonary Function Tests to Predict Complications After Chimeric Antigen Receptor T-Cell Therapy 肺功能测试在预测嵌合抗原受体t细胞治疗后并发症中的作用
IF 2.7 4区 医学
Clinical Lymphoma, Myeloma & Leukemia Pub Date : 2025-01-28 DOI: 10.1016/j.clml.2025.01.019
Jeremy Walder , Felipe Soto-Lanza , Lei Feng , Sairah Ahmed , Sattva Neelapu , Amy Ayers , Horiana B. Grosu , Saadia A. Faiz , Loretta Nastoupil , Ajay Sheshadri
{"title":"Role of Pulmonary Function Tests to Predict Complications After Chimeric Antigen Receptor T-Cell Therapy","authors":"Jeremy Walder ,&nbsp;Felipe Soto-Lanza ,&nbsp;Lei Feng ,&nbsp;Sairah Ahmed ,&nbsp;Sattva Neelapu ,&nbsp;Amy Ayers ,&nbsp;Horiana B. Grosu ,&nbsp;Saadia A. Faiz ,&nbsp;Loretta Nastoupil ,&nbsp;Ajay Sheshadri","doi":"10.1016/j.clml.2025.01.019","DOIUrl":"10.1016/j.clml.2025.01.019","url":null,"abstract":"<div><h3>Background</h3><div>Chimeric antigen receptor T-cell therapy (CAR-T) has transformed the treatment of certain hematologic malignancies, but toxicities limit efficacy. The role of pre-CAR-T pulmonary function testing (PFT) to predict toxicities is unclear.</div></div><div><h3>Objective</h3><div>Our aim was to examine the association between PFTs obtained prior to CAR-T and subsequent complications in patients with lymphoma.</div></div><div><h3>Study Design</h3><div>We conducted a retrospective study of patients who underwent standard-of-care CAR-T at our institution with pretherapy PFTs. Race-neutral normative equations from the Global Lung Initiative were used to generate percent-predicted values (PPV) for spirometry and diffusing capacity of the lungs for carbon monoxide (DLCO). Lung function score (LFS) was calculated by combining the forced expiratory volume in the first second (FEV<sub>1</sub>) and the diffusion capacity of the lung for carbon monoxide corrected for hemoglobin level (cDLCO) in an equally distributed manner, with higher score denoting worse lung function. Binary logistic regression models were used to compare the association of PFTs with complications after CAR-T. Cox regression models were additionally fit to identify predictors of mortality.</div></div><div><h3>Results</h3><div>Of 218 individuals who underwent CAR-T therapy, 66 had PFTs performed within 12 months prior to lymphodepletion. Higher LFS was associated with higher risk of CRS (OR 4.3, 95% CI, 1.4-29, <em>P</em> = .048), after adjusting for lines of treatment. When adjusting for lines of treatment, both FEV<sub>1</sub> (OR = 0.96, 95% CI, 0.93-0.99, <em>P</em> = .05) and FVC (OR = 0.96, 95% CI 0.92-0.99, <em>P</em> = .03) are protective for ICANS. PFT abnormalities were not associated with early or late mortality.</div></div><div><h3>Conclusion</h3><div>The combination of pre-CAR-T spirometry and cDLCO may help clinicians understand the risk for toxicities after CAR-T cell therapy.</div></div>","PeriodicalId":10348,"journal":{"name":"Clinical Lymphoma, Myeloma & Leukemia","volume":"25 7","pages":"Pages 520-526"},"PeriodicalIF":2.7,"publicationDate":"2025-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143499439","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Follicular Lymphoma: Paving the Path to Cures Through Philanthropy 滤泡性淋巴瘤:通过慈善事业为治疗铺平道路。
IF 2.7 4区 医学
Clinical Lymphoma, Myeloma & Leukemia Pub Date : 2025-01-28 DOI: 10.1016/j.clml.2025.01.020
Mitchell R. Smith , Michel Azoulay , Lee M. Greenberger
{"title":"Follicular Lymphoma: Paving the Path to Cures Through Philanthropy","authors":"Mitchell R. Smith ,&nbsp;Michel Azoulay ,&nbsp;Lee M. Greenberger","doi":"10.1016/j.clml.2025.01.020","DOIUrl":"10.1016/j.clml.2025.01.020","url":null,"abstract":"","PeriodicalId":10348,"journal":{"name":"Clinical Lymphoma, Myeloma & Leukemia","volume":"25 7","pages":"Pages e507-e509"},"PeriodicalIF":2.7,"publicationDate":"2025-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143457101","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
SOHO State of the Art Updates and Next Questions | Novel Immunotherapy Combinations for the Treatment of Indolent B-Cell Lymphoma SOHO最新进展和下一个问题|治疗惰性b细胞淋巴瘤的新免疫疗法组合。
IF 2.7 4区 医学
Clinical Lymphoma, Myeloma & Leukemia Pub Date : 2025-01-28 DOI: 10.1016/j.clml.2025.01.021
Tony Z. Zhuang , Chen Zhang , Paolo Strati
{"title":"SOHO State of the Art Updates and Next Questions | Novel Immunotherapy Combinations for the Treatment of Indolent B-Cell Lymphoma","authors":"Tony Z. Zhuang ,&nbsp;Chen Zhang ,&nbsp;Paolo Strati","doi":"10.1016/j.clml.2025.01.021","DOIUrl":"10.1016/j.clml.2025.01.021","url":null,"abstract":"<div><div>Chemoimmunotherapy (CIT) is the standard frontline treatment for advanced indolent non-Hodgkin lymphomas (iNHL). While lenalidomide-based immunotherapy remains the standard of care for relapsed iNHL, its frontline use is limited, due to nonsuperiority as compared to CIT. Agents that engage T-cells, polarize macrophage phenotype to a more antitumoral phenotype, and/or to target epigenetic pathways could enhance immunotherapy. We summarize in this review safety plus efficacy data from published and/or ongoing clinical trials investigating the combination of lenalidomide-based immunotherapy with T-cell engagers (including anti-CD3/CD20 bispecific antibodies), macrophage-targeting agents (including BTK inhibitors and anti-CD47 antibodies), and epigenetic modifiers (including EZH2 inhibitors). We also summarize the activity in iNHL of agents targeting antigens other than CD20 (including CD19 and CD79b), and novel immunotherapies and cellular therapies (including NK-cell based treatments). The therapeutic landscape of iNHL is soon to significantly change.</div></div>","PeriodicalId":10348,"journal":{"name":"Clinical Lymphoma, Myeloma & Leukemia","volume":"25 7","pages":"Pages 455-464"},"PeriodicalIF":2.7,"publicationDate":"2025-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143514876","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
A First-in-Human Phase I Study of LOXO-338, an Oral Selective Bcl-2 Inhibitor, in Patients With Advanced Hematologic Malignancies LOXO-338是一种口服选择性Bcl-2抑制剂,用于晚期血液恶性肿瘤患者的首次人体I期研究。
IF 2.7 4区 医学
Clinical Lymphoma, Myeloma & Leukemia Pub Date : 2025-01-28 DOI: 10.1016/j.clml.2025.01.018
Michal Kwiatek , Guru Subramanian Guru Murthy , Marc Hoffmann , Benoit Tessoulin , Alexey Danilov , Alvaro J. Alencar , Nirav N. Shah , Hervé Ghesquieres , Steven Le Gouill , Wojciech Jurczak , Hongmei Han , Eunice Yuen , Vishalkumar Patel , Yingying Guo-Avrutin , James M. Pauff , Lindsey E. Roeker
{"title":"A First-in-Human Phase I Study of LOXO-338, an Oral Selective Bcl-2 Inhibitor, in Patients With Advanced Hematologic Malignancies","authors":"Michal Kwiatek ,&nbsp;Guru Subramanian Guru Murthy ,&nbsp;Marc Hoffmann ,&nbsp;Benoit Tessoulin ,&nbsp;Alexey Danilov ,&nbsp;Alvaro J. Alencar ,&nbsp;Nirav N. Shah ,&nbsp;Hervé Ghesquieres ,&nbsp;Steven Le Gouill ,&nbsp;Wojciech Jurczak ,&nbsp;Hongmei Han ,&nbsp;Eunice Yuen ,&nbsp;Vishalkumar Patel ,&nbsp;Yingying Guo-Avrutin ,&nbsp;James M. Pauff ,&nbsp;Lindsey E. Roeker","doi":"10.1016/j.clml.2025.01.018","DOIUrl":"10.1016/j.clml.2025.01.018","url":null,"abstract":"<div><h3>Background</h3><div>LOXO-338 is a novel, orally bioavailable small-molecule inhibitor of Bcl-2, designed to achieve selectivity for Bcl-2 over Bcl-xL, thus avoiding dose-limiting thrombocytopenia associated with Bcl-xL inhibition. This first-in-human, open-label, Phase 1 study investigated LOXO-338 in patients with chronic lymphocytic leukemia (CLL), small lymphocytic lymphoma (SLL), or B-cell non–Hodgkin lymphoma (NHL) (NCT05024045).</div></div><div><h3>Patients and Methods</h3><div>Patients with histologically confirmed advanced B-cell malignancies who had received ≥ 2 prior therapies were enrolled in Phase 1 dose escalation (interval 3 + 3 design). LOXO-338 was administered orally as 50 to 300 mg once-daily dose until discontinuation due to progressive disease or unacceptable toxicity. The primary objective was to determine the maximum tolerated dose (MTD)/recommended Phase 2 dose of LOXO-338. Secondary objectives included safety, tolerability, pharmacokinetics, and preliminary antitumor activity.</div></div><div><h3>Results</h3><div>In total, 27 patients with CLL/SLL (<em>n</em> = 10) or NHL (<em>n</em> = 17) were treated. No dose-limiting toxicities occurred and the MTD was not reached. Treatment-emergent adverse events occurred in 23 patients (85%); anemia (22%) and fatigue (22%) were the most prevalent. Treatment-related adverse events (TRAEs) occurred in 15% and were mostly grade 1 (11%) or 2 (4%); grade ≥ 3 or serious TRAEs were not reported. Tumor lysis syndrome was not observed. The overall response rate was 19% (95% CI: 6.3, 38.1) and disease control rate was 67% (95% CI: 46, 83.5). LOXO-338 was orally bioavailable with dose-dependent increases in exposure.</div></div><div><h3>Conclusion</h3><div>LOXO-338 was well tolerated with a favorable safety profile in previously treated patients with advanced hematologic malignancies. Preliminary efficacy was observed in this heavily pretreated population supporting further investigation.</div></div>","PeriodicalId":10348,"journal":{"name":"Clinical Lymphoma, Myeloma & Leukemia","volume":"25 7","pages":"Pages 512-519"},"PeriodicalIF":2.7,"publicationDate":"2025-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143499406","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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