Venetoclax

Eli Lilly is moving to expand the label for Jaypirca (pirtobrutinib) after reporting a fourth Phase III leukaemia study, with new data showing the non-covalent BTK inhibitor significantly prolonged progression-free survival (PFS) when added to a time-limited venetoclax-based regimen.The results "outperformed our expectations," stated Jacob Van Naarden, Lilly Oncology president, in a release Monday.The BRUIN CLL-322 study enrolled 639 patients, most of whom had prior exposure to covalent BTK inhibitors. Participants were randomly assigned to receive Jaypirca added to venetoclax plus rituximab, or venetoclax plus rituximab alone. Treatment in both study arms was given for up to two years, after which patients do not take any CLL therapy until their disease progresses.OS trending in favourThe Jaypirca regimen outperformed venetoclax and rituximab alone in patients with relapsed or refractory chronic lymphocytic leukemia or small lymphocytic lymphoma (CLL/SLL), meeting the study's main goal. The key secondary endpoint of overall survival is "trending in favour" of the Jayprica combo arm, though the data are still immature, according to Lilly.The regimen's overall safety profile was consistent with the known profiles of each drug. More results will be presented at a medical congress and submitted for peer review.Lilly will submit the results to regulators later this year to broaden Jaypirca's use beyond its current approvals in previously treated CLL/SLL following a covalent BTK inhibitor and in later-line mantle cell lymphoma."Modern CLL treatment regimens provide such durable disease control that the vast majority of patients see their entire disease course managed by only one or two lines of therapy," Van Naarden said. The BRUIN CLL-322 results "reinforce the potential role that [Jaypirca] may have, whether as a time-limited combination as a second line treatment or as a continuously dosed monotherapy in either line of therapy."Monday's readout is the latest to emerge from the BRUIN programme. The company previously reported results from the Phase III BRUIN CLL-321 trial in post-covalent BTK inhibitor patients testing Jaypirca against investigator's choice of Gilead Sciences' Zydelig (idelalisib) plus rituximab or bendamustine plus rituximab.Last year, it also unveiled data from BRUIN CLL-313 in which patients with treatment-naïve disease received either Jaypirca or bendamustine plus rituximab; and BRUIN CLL-314, which compared Jaypirca head-to-head with AbbVie and Johnson & Johnson's Imbruvica (ibrutinib) in patients who were treatment-naïve or BTK inhibitor-naïve.

日报精选医学文献 今日精选20篇医学文献，查看更多请点击阅读原文 本文支持继续浏览摘要内容；完整摘要、收藏文章、订阅管理等完整功能，请前往小程序「医研日新」。前往小程序查看更多与订阅收藏 1. Emotional well-being at diagnosis may indicate future mental health risk in patients with juvenile idiopathic arthritis: data from the German inception cohort ICON. [Arthritis, Juvenile] 多中心研究 | RMD open | 2026-04-09 | IF 5.1 AIJIA患者确诊初期的情绪功能评估可预测远期心理健康风险，建议将生活质量量表纳入常规随访以早期干预。 摘要To determine the prevalence of depressive and anxiety symptoms among young people 7 years and 9 years after inclusion in the multicentre, prospective inception cohort (ICON) of newly diagnosed patients with juvenile idiopathic arthritis (JIA) in Germany, and to identify factors associated with mental health problems at study inclusion and in the course of the disease. Patients and controls (health...查看完整摘要 2. Daratumumab in high-risk MGUS and low-risk smoldering myeloma: results of the Phase II D-PRISM study. [Hypertension] Nature communications | 2026-04-08 | IF 14.7 AI单药达雷妥尤单抗在早期MGUS/SMM中安全性可接受但疗效有限，提示精准筛选患者及联合治疗策略可能优于单药早期干预。 摘要Daratumumab is approved for patients with multiple myeloma (MM) and high-risk smoldering MM (HR-SMM). However, HR-SMM is often as genomically complex as MM, suggesting it may be too advanced for single-agent intervention. We report on a Phase II trial of single-agent daratumumab in patients with earlier-stage disease, including high-risk monoclonal gammopathy of undetermined significance and low-r...查看完整摘要 3. Chitinase-like proteins de-N-glycosylating CD36 modify cholesterol metabolism in atherosclerotic macrophages. [Atherosclerosis] Nature communications | 2026-04-08 | IF 14.7 AI针对CHI3L2的中和抗体可能成为动脉粥样硬化新型治疗策略，为高危患者提供精准干预手段。 摘要Polymorphisms of mouse chitinase-like protein 3 (Chil3), a member of the mammalian chitinase-like protein (CLP) family, have been demonstrated to be associated with inflammatory diseases by regulating lipid metabolism. However, the specific immunomodulatory impacts of CLPs, mainly mouse CHIL3 and its human functional homologue chitinase-3-like 2 (CHI3L2), on macrophage cholesterol metabolism and a...查看完整摘要 4. Neoadjuvant and adjuvant nivolumab associated with irreversible electroporation in patients with BCLC a hepatocellular carcinoma and high risk of recurrence (NIVOLEP trial). [Carcinoma] Hepatology (Baltimore, Md.) | 2026-04-08 | IF 12.9 AI免疫检查点抑制剂与IRE联合治疗可降低HCC局部复发率，免疫激活与病理缓解相关，为高危HCC患者的综合治疗提供新策略。 摘要Irreversible electroporation (IRE) is a non-thermal ablation technique suited for difficult-to-treat hepatocellular carcinoma (HCC) with one-year local recurrence (LR) rates above 50. We hypothesized that peri-procedural immunotherapy could synergize with IRE to decrease local recurrence. NIVOLEP is a multicenter phase 2 trial evaluating nivolumab combined with IRE in patients with BCLC A HCC. Pat...查看完整摘要 5. Correction: Exploiting PRMT5 as a target for combination therapy in mantle cell lymphoma characterized by frequent ATM and TP53 mutations. [Lymphoma] Published Erratum | Blood cancer journal | 2026-04-08 | IF 12.9 AIPRMT5靶向联合治疗在ATM/TP53突变型套细胞淋巴瘤中具有治疗潜力，临床医生应关注该分子标志物的检测以指导精准治疗策略。 6. Dietary intake and the risk of monoclonal gammopathy of undetermined significance: results from the population-based iStopMM screening study. [Multiple Myeloma] Blood cancer journal | 2026-04-08 | IF 12.9 AI对于临床实践而言，该研究结果表明饮食干预可能不是预防MGUS进展为MM的主要策略，但仍需关注高乳制品摄入与IgA型MGUS的潜在关联。 摘要Monoclonal gammopathy of undetermined significance (MGUS) is the asymptomatic precursor of multiple myeloma (MM) and related disorders. Understanding the causes of MGUS is key to elucidating the causes of these malignancies. The association of MGUS and diet, including dietary patterns, remains unclear. We therefore assessed the relationship between diet and MGUS in the iStopMM a nationwide screeni...查看完整摘要 7. Filament sensing tension: A bionic artificial tendon for self-force-regulated artificial muscle-driven wearable robotics. [Stroke] Science advances | 2026-04-08 | IF 11.7 AI仿生ExoTendon可实现可穿戴外骨骼的力自适应调节，为中风后步态康复提供精准、个性化的力辅助支持，有望提升康复效率。 摘要Artificial muscles have been in development for decades and play a crucial role in the field of wearable robotics. However, a universal device for both sensing and regulating forces in artificial muscles is still absent, rendering scenario-required force control unfeasible. Inspired by Golgi tendon organs, this work proposes bionic ExoTendon for force sensing and regulating in artificial muscles a...查看完整摘要 8. From vibrations to function: Spectroscopic detection and quantification of π-π stacking in drug-responsive protein complexes. [COVID-19] Science advances | 2026-04-08 | IF 11.7 AITRIP技术通过监测苯丙氨酸环呼吸振动模式，可实时、无标记地评估药物与靶蛋白的结合强度及抗病毒效力，为优化COVID-19药物设计提供快速、定量的评估工具。 摘要Aromatic π-π stacking interactions are fundamental to protein architecture, molecular recognition, and drug efficacy, yet directly quantifying them under near-physiological conditions has remained challenging. Here, we use a recently developed spectroscopic platform, thermostable Raman interaction profiling (TRIP), that enables direct, label-free detection and quantification of aromatic π-π intera...查看完整摘要 9. Microtubules in the axon are GDP bound but adopt a stable GTP-like expanded state. [Stroke] Nature structural & molecular biology | 2026-04-08 | IF 10.1 AI这项研究揭示了神经元轴突微管的独特稳定性机制，可能为理解神经发育异常和神经退行性疾病的微管功能障碍提供新靶点。 摘要Microtubules scaffold cells, supporting signaling and cargo transport. They assemble from GTP-tubulin, which hydrolyzes to GDP-tubulin during polymerization. GTP-microtubule lattices are stable; GDP lattices depolymerize rapidly. In vitro, hydrolysis triggers lattice compaction. Lattice spacing regulates motors and microtubule-associated proteins; however, the conformation of tubulin in microtubul...查看完整摘要 10. Recurrent Genomic Alterations in BCRi-Experienced CLL Patients Treated With Venetoclax: Extended Phase 2 Follow-Up. [Lymphoma] 信函 | American journal of hematology | 2026-04-08 | IF 10.1 AIBCRi经治CLL患者使用维奈托克后存在特定的基因组再现性改变模式，提示需在治疗前和治疗中进行全面的基因组监测以指导治疗决策。 11. The AGPS regulatory variant rs113671272 confers esophageal squamous cell carcinoma susceptibility through allele-specific MEIS3 binding and NF-κB activation in Chinese populations. [Carcinoma] EBioMedicine | 2026-04-08 | IF 9.7 AIrs113671272变异通过MEIS3/AGPS/NF-κB轴增加ESCC风险，A等位基因携带者预后较差，AGPS有望成为高风险中国人群ESCC早筛及精准干预的新靶点。 摘要Esophageal squamous cell carcinoma (ESCC) demonstrates pronounced ethnic disparities, being prevalent in Asian populations. However, the genetic mechanisms underlying this disparity remain poorly understood. This study aims to characterise the functional contribution of the regulatory variant rs113671272 in alkylglycerone phosphate synthase (AGPS) to ESCC susceptibility and prognosis in Chinese co...查看完整摘要 12. Disease insights from brain somatic mosaicism. [Neurodegenerative Diseases] 综述 | Experimental & molecular medicine | 2026-04-08 | IF 9.5 AI脑体细胞嵌合变异分析为神经精神疾病的精准诊治提供了基因组层面的新视角，有助于识别疾病特异性体细胞突变。 摘要Brain somatic mosaicism (BSM) refers to genome variation within brain cells that results from accumulated postzygotic mutations. These mutations can be used to understand cell lineage, molecular dynamics and disease processes. Unlike most other organs, brain cells are mostly fixed in position and not replaced throughout life. Thus, assessing mosaic variants (MVs) within the brain, including their ...查看完整摘要 13. Structure basis for C-C chemokine receptor 4 modulation by orthosteric and allosteric antagonists. [Lymphoma] Proceedings of the National Academy of Sciences of the United States of America | 2026-04-08 | IF 9.4 AI该研究首次系统解析了CCR4与多种临床候选药物的结合模式，明确了正构与别构拮抗剂的不同作用机制，为临床医生选择CCR4靶向治疗方案及未来药物开发提供了关键的分子结构依据。 摘要The chemokine system, comprising a network of chemokines and their receptors, orchestrates leukocyte migration and plays a central role in immune surveillance and inflammation. Targeting this system has emerged as a promising strategy in cancer immunotherapy and the treatment of immune-related disorders. C-C chemokine receptor 4 (CCR4), the receptor for chemokines CCL17 and CCL22, is a clinically ...查看完整摘要 14. SARS-CoV-2 and MERS-CoV disrupt host protein synthesis via nsp1 with differential effects on the integrated stress response. [COVID-19] Proceedings of the National Academy of Sciences of the United States of America | 2026-04-08 | IF 9.4 AISARS-CoV-2通过nsp1激活PERK通路诱导eIF2α磷酸化从而抑制宿主蛋白合成，而MERS-CoV采取不同策略，提示针对不同冠状病毒抗病毒药物研发需个体化策略。 摘要Coronaviruses pose a serious threat to public health, driving the need for antiviral therapeutics and vaccines. Therefore, it is paramount to understand how this family of viruses evades cellular antiviral responses and establishes productive infection. The conserved coronavirus nonstructural protein 1 (nsp1) has been shown to inhibit host protein synthesis and, in some coronaviruses, promote host...查看完整摘要 15. Loss of FoxO in skeletal muscle leads to disrupted muscle metabolism and exacerbates starvation-induced hepatic steatosis. [Obesity] Proceedings of the National Academy of Sciences of the United States of America | 2026-04-08 | IF 9.4 AI骨骼肌FoxO转录因子可能成为治疗代谢相关脂肪性肝病的新靶点，通过调控肌肉脂质代谢间接改善肝脏脂肪沉积。 摘要Up to a third of the global population is afflicted by metabolic dysfunction-associated steatotic liver disease with excessive triglyceride accumulation in the liver. Prolonged fasting rapidly causes hepatic steatosis via excessive influx of free fatty acids from adipose tissue. However, it is unclear whether skeletal muscle is involved in the etiology of hepatic steatosis during starvation. Here,...查看完整摘要 16. Interpretable Multimodal Learning for Cardiovascular Hemodynamics Assessment. [Heart Failure] IEEE transactions on medical imaging | 2026-04-08 | IF 8.9 AI该可解释多模态学习方法可无创预测肺动脉楔压，为大规模筛查心力衰竭高危患者提供了高效、可靠的临床决策支持工具。 摘要Pulmonary Arterial Wedge Pressure (PAWP) is an essential cardiovascular hemodynamics marker to detect heart failure. In clinical practice, Right Heart Catheterization is considered a gold standard for assessing cardiac hemodynamics while non-invasive methods are often needed to screen high-risk patients from a large population. In this paper, we propose a multimodal learning pipeline to predict PA...查看完整摘要 17. Epilepsy surgery outcomes and their determinants: a systematic review and individual patient data meta-analysis. [Epilepsy] Journal of neurology, neurosurgery, and psychiatry | 2026-04-08 | IF 8.7 AI颞叶和岛叶癫痫手术成功率最高（~68%），肿瘤患者预后显著优于其他病理类型，多脑叶切除预后较差，提示临床应充分评估患者特征以优化手术决策。 摘要Despite advances in epilepsy surgery, seizure freedom is achieved in only ~50-70% of cases, highlighting the need to better understand factors driving surgical success. A preregistered systematic review and individual patient data meta-analysis was conducted on studies reporting clinical outcomes in epilepsy surgery, based on a comprehensive literature search through August 2024. Data were extract...查看完整摘要 18. Folic Acid Intake, Genetic Variations, and DNA Methylation in Hypertensive Disorders of Pregnancy : A Prospective Cohort and Epigenome-Wide Association Study. [Hypertension] European journal of preventive cardiology | 2026-04-08 | IF 8.4 AI孕前合理补充叶酸可优化叶酸代谢平衡，但需关注遗传背景对叶酸代谢的影响，过量未代谢叶酸可能反而增加妊娠期高血压风险。 摘要Research on folate levels in relation to hypertensive disorders of pregnancy (HDP) has yielded inconsistent results, often overlooking the roles of folic acid intake, genetic variations in folate metabolism, and DNA methylation. This study investigates the relationships among these factors and HDP risk. A prospective cohort of 4,079 Chinese pregnant women (2022-2024) assessed the association betwe...查看完整摘要 19. Hypersensitivity to Excipients in Drugs: An EAACI Position Paper. [Drug Hypersensitivity] Allergy | 2026-04-08 | IF 8.2 AI对不明原因多次对无关药物发生过敏反应的患者，应警惕辅料过敏可能，查阅药品说明书并针对性进行纯辅料及对照药物检测以明确诊断，避免反复暴露于致敏辅料。 摘要Drugs contain active pharmaceutical ingredients and excipients, compounds which enhance the pharmacokinetics, stability and palatability of the pharmaceutical formulation. While most drug hypersensitivity reactions (DHR) are caused by active ingredients, excipients may also be involved. Excipient-related DHR are easily overlooked and may lead to repeated anaphylaxis in patients exposed to pharmace...查看完整摘要 20. Perforin-2 enhances antigen-specific CTL immune response by promoting cross presentation. [Sepsis] Cell death & disease | 2026-04-08 | IF 8.1 AI穿孔素-2可能成为增强肿瘤免疫治疗效果的新靶点，通过调控DCs的交叉递呈功能来优化CD8⁺ T细胞抗肿瘤应答。 摘要Antigen cross-presentation is essential for initiating CD8+ cytotoxic T lymphocyte (CTL) response. Perforin-2 (P2), a pore-forming protein constitutively expressed in dendritic cells (DCs), has been implicated in endocytic cargo escape, but its role in cross-presentation remains poorly defined. Here, we show that loss of P2 markedly impairs DC-mediated cross-presentation of both soluble...查看完整摘要 在小程序获取完整功能 收藏文章、管理订阅、查看本期完整摘要与个性化内容，请前往小程序「医研日新」。 前往小程序查看更多内容 免责声明：仅供学术交流参考，不构成任何医学建议或诊疗指导