Blood Neoplasia最新文献

Ibrutinib and venetoclax in combination for chronic lymphocytic leukemia: synergy in practice 伊布替尼和 venetoclax 联合治疗慢性淋巴细胞白血病：实践中的协同作用

Blood Neoplasia Pub Date : 2024-09-01 DOI: 10.1016/j.bneo.2024.100034

{"title":"Ibrutinib and venetoclax in combination for chronic lymphocytic leukemia: synergy in practice","authors":"","doi":"10.1016/j.bneo.2024.100034","DOIUrl":"10.1016/j.bneo.2024.100034","url":null,"abstract":"<div><h3>Abstract</h3><p>The combination of ibrutinib and venetoclax has emerged as a promising therapeutic strategy for patients with chronic lymphocytic leukemia (CLL). Preclinical investigations demonstrated a synergistic antitumor effect through multiple mechanisms, providing a robust foundation for translating this regimen into clinical trials. Beyond the dual inhibition by 2 small molecules, another innovative concept being tested with this combination is the use of measurable residual disease (MRD)–driven treatment vs fixed-duration treatment to meet the escalating demand for oral, convenient, cost-effective, and time-limited therapeutic approaches. The clinical translation of this combination has yielded remarkable outcomes with significant improvements in the progression-free survival and overall survival rates for both treatment-naïve patients and those with relapsed/refractory CLL. Notably, a substantial proportion of patients achieved undetectable MRD. Clinical trial updates following the initial published results have shown consistency and durability of responses over time. In this review, the initial investigator-initiated trial results for ibrutinib and venetoclax are discussed, several multicenter clinical trial designs and outcomes are examined, variables such as chromosome 17p deletion that influence treatment responses are addressed, and the safety of the regimen is discussed. In addition, we reviewed the usage of this combination in other B-cell malignancies and discussed how current knowledge can be used for shaping the future CLL treatment regimens.</p></div>","PeriodicalId":100189,"journal":{"name":"Blood Neoplasia","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2950328024000347/pdfft?md5=6d685af44e4971629738466491360299&pid=1-s2.0-S2950328024000347-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142095128","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Augmented use of L-asparaginase markedly improves AYA ALL outcomes: FBMTG prospective MRD2014 study 加强使用 L-天冬酰胺酶可显著改善 AYA ALL 的预后：FBMTG前瞻性MRD2014研究

Blood Neoplasia Pub Date : 2024-09-01 DOI: 10.1016/j.bneo.2024.100033

{"title":"Augmented use of L-asparaginase markedly improves AYA ALL outcomes: FBMTG prospective MRD2014 study","authors":"","doi":"10.1016/j.bneo.2024.100033","DOIUrl":"10.1016/j.bneo.2024.100033","url":null,"abstract":"<div><h3>Abstract</h3><p>The enhanced utilization of native L-asparaginase (L-Asp) aims to improve treatment outcomes for adult patients with non-Philadelphia chromosome (Ph) acute lymphoblastic leukemia (ALL). In this measurable residual disease 2014 (MRD2014) study, we modified our protocol to include an augmented dose of native L-Asp. Compared with former MRD2008, the total dose of L-Asp was raised from 36 000 U/m<sup>2</sup> to 232 000 U/m<sup>2</sup> in patients aged 16 to 35 and from 36 000 U/m<sup>2</sup> to 132 000 U/m<sup>2</sup> in patients aged 36 to 65 years. Adult patients with ALL were enrolled between January 2014 and December 2019 based on the following eligibility criteria: non-L3 ALL, age 16 to 65 years, Eastern Cooperative Oncology Group performance status of 0 to 2, and adequate liver and kidney functions (serum bilirubin ≤ 2.0 mg/dL; serum creatinine ≤ 2.0 mg/dL). The median follow-up time was 1128 days (range, 35-2400). A total of 81 patients with non-Ph ALL (40 males and 41 females; median age, 39 years [range, 16-64]) in whom MRD status was assessed were included. Complete remission was achieved in 72 patients (89%). The probability of 3-year event-free survival (EFS) and overall survival (OS) in these patients were 55% and 72%, respectively. The outcomes for patients aged 16 to 35 years demonstrated remarkable improvement. The 3-year EFS of MRD2008 at 45% significantly increased to 71% for MRD2014. Our study unequivocally demonstrated the beneficial effects of augmented use of L-Asp in this adolescent and young adult population. This trial was registered at UMIN Clinical Trials Registry as #UMIN000012382.</p></div>","PeriodicalId":100189,"journal":{"name":"Blood Neoplasia","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2950328024000335/pdfft?md5=bbf499ae9c9b69c23bb21aa6d69f4833&pid=1-s2.0-S2950328024000335-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142095183","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

T-cell lymphoblastic lymphoma compared with T-cell acute lymphoblastic leukemia: similar subtypes and different fusions T 细胞淋巴细胞淋巴瘤与 T 细胞急性淋巴细胞白血病的比较：相似的亚型和不同的融合

Blood Neoplasia Pub Date : 2024-09-01 DOI: 10.1016/j.bneo.2024.100029

引用次数: 0

Clinical and pathological features of pediatric peripheral T-cell lymphoma after solid organ transplantation 实体器官移植后小儿外周T细胞淋巴瘤的临床和病理特征

Blood Neoplasia Pub Date : 2024-08-28 DOI: 10.1016/j.bneo.2024.100039

引用次数: 0

CD38-CAR human NK cells in combination with ATRA enhance cytotoxicity against CD38-expressing hematologic malignancies CD38-CAR 人 NK 细胞与 ATRA 结合使用可增强对表达 CD38 的血液恶性肿瘤的细胞毒性

Blood Neoplasia Pub Date : 2024-07-31 DOI: 10.1016/j.bneo.2024.100032

{"title":"CD38-CAR human NK cells in combination with ATRA enhance cytotoxicity against CD38-expressing hematologic malignancies","authors":"","doi":"10.1016/j.bneo.2024.100032","DOIUrl":"10.1016/j.bneo.2024.100032","url":null,"abstract":"<div><h3>Abstract</h3><div>CD38 is a metabolically active enzyme broadly expressed on the surface of normal and malignant hematologic cells. It has been targeted clinically with anti-CD38 monoclonal antibodies (mAbs), for which efficacy may be limited by natural killer (NK)–cell fratricide. Isatuximab is an anti-CD38 mAb that uniquely inhibits CD38 metabolic activity. Here, we used CRISPR/adeno-associated virus (AAV) to generate fratricide–resistant and metabolically–enhanced CD38<sup>KO</sup>/CD38-chimeric antigen receptor (CAR) NK cells using 2 isatuximab-based CD38 single-chain variable fragments (scFvs; reversing heavy and light chain orientation) on the same CD8α/4-1BB/CD3ζ base, and we demonstrate their activity against a range of CD38<sup>+</sup> hematologic malignancies (acute myeloid leukemia, multiple myeloma, Burkitt lymphoma, and T-cell leukemia/lymphoma). The cytotoxicity of the CAR NK cells was enhanced by upregulating CD38 expression on the malignant targets with all-trans retinoic acid (ATRA). By generating CD38<sup>KO</sup>/CD38-CAR T cells using the same engineering approach, we show that the CAR NK cells had higher cytotoxicity than CAR T cells against all hematologic tumor targets. Additionally, AAVS1<sup>KO</sup>/CD38-CAR NK cells were capable of targeting CD38 without experiencing fratricide and have a similar enhanced metabolic activity via the inhibitory activity of the cis-acting isatuximab-based scFv. Finally, we report fratricide-resistant CD38-CAR NK cells with enhanced metabolism and cytotoxicity toward CD38<sup>+</sup> hematologic malignancies, further increased by combination treatment with ATRA.</div></div>","PeriodicalId":100189,"journal":{"name":"Blood Neoplasia","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142319604","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Effect of clofarabine and fludarabine exposure on outcome after pediatric allogeneic hematopoietic cell transplantation 氯法拉滨和氟达拉滨暴露对小儿异基因造血细胞移植术后结果的影响

Blood Neoplasia Pub Date : 2024-07-17 DOI: 10.1016/j.bneo.2024.100030

引用次数: 0

Data-driven flow cytometry classification of blast differentiation in older patients with acute myeloid leukemia 数据驱动的流式细胞仪对老年急性髓性白血病患者的胚泡分化进行分类

Blood Neoplasia Pub Date : 2024-06-19 DOI: 10.1016/j.bneo.2024.100027

引用次数: 0

Correlation between peripheral blood and bone marrow mutations among patients with MDS from the National MDS Study 全国骨髓增生异常综合征研究骨髓增生异常综合征/新生物患者外周血和骨髓突变之间的相关性

Blood Neoplasia Pub Date : 2024-06-12 DOI: 10.1016/j.bneo.2024.100026

引用次数: 0

An EMT-like signature as a potential driver of myeloid sarcoma 髓系肉瘤的潜在驱动因素--EMT 样特征

Blood Neoplasia Pub Date : 2024-06-12 DOI: 10.1016/j.bneo.2024.100024

引用次数: 0

Impact of ibrutinib dose adjustment on TTNT in first-line CLL/SLL: a real-world analysis using target trial emulation 伊布替尼剂量调整对一线CLL/SLL患者TTNT的影响：利用目标试验模拟进行的真实世界分析

Blood Neoplasia Pub Date : 2024-06-10 DOI: 10.1016/j.bneo.2024.100022

{"title":"Impact of ibrutinib dose adjustment on TTNT in first-line CLL/SLL: a real-world analysis using target trial emulation","authors":"","doi":"10.1016/j.bneo.2024.100022","DOIUrl":"10.1016/j.bneo.2024.100022","url":null,"abstract":"<div><h3>Abstract</h3><p>Ibrutinib, a once-daily Bruton tyrosine kinase inhibitor, is a standard-of-care first-line (1L) treatment for patients with chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL). Dosing flexibility (adjustment to daily dose of <420 mg/d) with ibrutinib can help prevent recurrence or worsening of adverse events while maintaining long-term efficacy. This study compared time to next treatment among patients with CLL/SLL in the United States initiating 1L single-agent ibrutinib at 420 mg/d (index date) and staying on this dose vs patients with dose adjustment (DA) within 3 to 12 months. Two databases were used: Komodo claims (a majority from community practices) and Acentrus electronic medical records (from academic and nonteaching hospital systems). To account for immortal time bias (patients with DA survived on 1L therapy until DA) and overlap between follow-up time and definition of treatment strategies, a target trial emulation approach was used, in which patients were cloned at index date and contributed follow-up to both treatment strategy arms until deviation from the strategy. Among 3343 patients in Komodo (mean age: 67.5 years; 37.6% female) and 1171 patients in Acentrus (mean age: 70.4 years; 34.6% female) who initiated 1L single-agent ibrutinib 420 mg/d, 18.0% and 19.6%, respectively, had a DA. DA was not associated with an increased risk of having a next treatment in both databases (adjusted hazard ratio [95% confidence interval]: Komodo: 0.95 [0.80-1.14], Acentrus: 1.14 [0.80-1.62]). These findings suggest that a flexible dosing approach with ibrutinib may be effective in allowing patients to achieve optimal outcomes while remaining on long-term continuous 1L treatment.</p></div>","PeriodicalId":100189,"journal":{"name":"Blood Neoplasia","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2950328024000220/pdfft?md5=51d92c6d6c422926088b47d7e3e1747f&pid=1-s2.0-S2950328024000220-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141408894","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0