Mantle cell lymphoma (MCL)

  • 文章类型: Journal Article
    背景:随着慢性淋巴细胞白血病(CLL)和套细胞淋巴瘤(MCL)治疗的最新进展,医疗保健专家可能会面临挑战,根据最新证据为这些疾病的患者提供最佳护理,做出治疗和管理决策。本研究旨在确定特定的知识,技能,以及影响CLL和MCL治疗的信心差距,为未来的教育活动提供信息。
    方法:血液学家和血液肿瘤学家(HCP,n=224)来自法国(学术环境),德国,美国(学术和社区环境)回应了15分钟的定量需求评估调查,该调查测量了感知知识,技能,以及对CLL和MCL患者治疗和管理不同方面的信心水平,以及临床病例问题。进行描述性统计(交叉表)和卡方检验。
    结果:确定了四个教育需求领域:(1)治疗指南的次优知识;(2)分子测试的次优知识,以告知CLL/MCL治疗决策;(3)根据患者概况做出治疗决策时的次优技能(合并症,分子检测结果);和(4)挑战平衡毒性风险与治疗益处。超过三分之一的受访者表示,在选择合适的治疗方案和处方疗法时存在技能差距,并且缺乏启动和管理治疗的信心。MCL在患者评估的指南知识和技能方面存在较大差距,与CLL相比。
    结论:这项研究表明需要继续医学教育,特别是提高治疗指南的知识。并协助临床医生在面对具有特定合并症和/或分子检测结果的患者的临床决策情景时发展技能和信心,例如,通过基于案例的学习活动。
    BACKGROUND: With recent advancements in the treatment of chronic lymphocytic leukemia (CLL) and mantle cell lymphoma (MCL), healthcare specialists may face challenges making treatment and management decisions based on latest evidence for the optimal care of patients with these conditions. This study aimed to identify specific knowledge, skills, and confidence gaps impacting the treatment of CLL and MCL, to inform future educational activities.
    METHODS: Hematologists and hemato-oncologists (HCPs, n = 224) from France (academic settings), Germany, and the United States (academic and community settings) responded to a 15-minute quantitative needs assessment survey that measured perceived knowledge, skills, and confidence levels regarding different aspects of treatment and management of CLL and MCL patients, as well as clinical case questions. Descriptive statistics (cross tabulations) and Chi-square tests were conducted.
    RESULTS: Four areas of educational need were identified: (1) sub-optimal knowledge of treatment guidelines; (2) sub-optimal knowledge of molecular testing to inform CLL/MCL treatment decisions; (3) sub-optimal skills when making treatment decisions according to patient profile (co-morbidities, molecular testing results); and (4) challenges balancing the risk of toxicities with benefits of treatment. Over one-third of the respondents reported skill gaps when selecting suitable treatment options and prescribing therapies and reported a lack in confidence to initiate and manage treatment. Larger gaps in knowledge of guidelines and skills in patient assessment were identified in MCL, compared to CLL.
    CONCLUSIONS: This study suggests the need for continuing medical education specifically to improve knowledge of treatment guidelines, and to assist clinicians in developing skills and confidence when faced with clinical decision-making scenarios of patients with specific comorbidities and/or molecular test results, for example, through case-based learning activities.
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  • 文章类型: Journal Article
    在前线高剂量3期FIL-MCL0208试验(NCT02354313)中,8%的登记套细胞淋巴瘤(MCL)患者不能随机接受来那度胺(LEN)维持与自体干细胞移植(ASCT)后观察,由于血液学恢复不足,52%的开始LEN的患者,由于毒性需要减少剂量。因此,我们专注于CD34造血干细胞(PBSC)收获和回输对毒性和结果的作用。总的来说,90%(n=245)接受首次白细胞去除术的患者收集≥4×106PBSC/kg,2.6%(n=7)动员<4×106PBSC/kg,7.7%(n=21)未能收集。计划的第二次白细胞分离术获得了类似的结果,只有一个病人两次尝试都失败了。重新输注的PBSC的中位数计数为5×106/kg,从中性粒细胞减少症G4恢复的中位数时间为ASCT的10天。没有注意到动员亚型或再注入PBSC的数量对血液学恢复和LEN剂量减少的影响。在ASCT的中位随访75个月时,移植患者的PFS和OS分别为50%和73%,分别。ASCT后持续的G4中性粒细胞减少症(>10天)与更差的结果相关。在PFS和OS方面。总之,虽然手术对年轻的MCL患者来说是可行的,ASCT后持续的血细胞减少症仍然是一个重要问题:这可能阻碍有效的维持疗法的管理,可能增加复发率并对生存结局产生负面影响.
    In the frontline high-dose phase 3 FIL-MCL0208 trial (NCT02354313), 8% of enrolled mantle cell lymphoma (MCL) patients could not be randomised to receive lenalidomide (LEN) maintenance vs observation after autologous stem cell transplantation (ASCT) due to inadequate hematological recovery and 52% of those who started LEN, needed a dose reduction due to toxicity. We therefore focused on the role played by CD34 + hematopoietic stem cells (PBSC) harvesting and reinfusion on toxicity and outcome. Overall, 90% (n = 245) of enrolled patients who underwent the first leukapheresis collected ≥ 4 × 106 PBSC/kg, 2.6% (n = 7) mobilized < 4 × 106 PBSC/kg and 7.7% (n = 21) failed the collection. Similar results were obtained for the planned second leukapheresis, with only one patient failing both attempts. Median count of reinfused PBSC was 5 × 106/kg and median time to recovery from neutropenia G4 was 10 days from ASCT. No impact of mobilizing subtype or number of reinfused PBSC on hematological recovery and LEN dose reduction was noted. At a median follow-up of 75 months from ASCT, PFS and OS of transplanted patients were 50% and 73%, respectively. A long lasting G4 neutropenia after ASCT (> 10 days) was associated with a worse outcome, both in terms of PFS and OS. In conclusion, although the harvesting procedures proved feasible for younger MCL patients, long-lasting cytopenia following ASCT remains a significant issue: this can hinder the administration of effective maintenance therapies, potentially increasing the relapse rate and negatively affecting survival outcomes.
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  • 文章类型: Journal Article
    共价Bruton酪氨酸激酶抑制剂(BTKi)治疗代表了治疗复发或难治性套细胞淋巴瘤的重要进展。但是这些治疗方法并不能治愈,许多患者最终会复发。皮尔托替尼,一个高度选择性的,非共价(可逆)BTKi,抑制野生型和C481突变型BTK,具有相同的低nM效力,并且具有良好的口服药物学,无论BTK周转的内在速率如何,都可以在整个给药间隔内连续抑制BTK。Pirtobrutinib具有良好的耐受性,并且在先前治疗后预后不良的B细胞恶性肿瘤患者中表现出了有希望的疗效。包括共价BTKi。第三阶段,头对头,随机研究(NCT04662255)将评估吡托布替尼是否优于研究者选择的共价BTKi,BTKi-幼稚套细胞淋巴瘤。
    MCL是一种罕见的B细胞非霍奇金淋巴瘤,免疫系统的癌症.它始于淋巴结的一部分,称为地幔区,不寻常的B细胞聚集并排挤淋巴结中健康的B细胞,脾,脾骨髓和/或其他器官。MCL可由不适当的细胞信号传导引起。BTK已被确定为异常细胞信号传导的关键驱动因素,阻断BTK已被证明有助于杀死癌细胞。共价(不可逆的)BTK抑制剂已经促进了MCL的治疗,但是这些治疗的有效性受到副作用和治疗抗性的限制。皮尔托替尼,一种非共价(可逆)BTK抑制剂,已被证明具有可控的副作用,并且在先前治疗后对MCL患者有效,包括用共价BTK抑制剂治疗。BRUINMCL-321研究将pirtobrutinib与三种目前批准的共价BTK抑制剂(ibrutinib,阿卡拉布替尼或扎努布替尼),从未接受过任何形式的BTK抑制剂的MCL患者。这项试验将研究有多少人患有这种疾病而不会变得更糟。像其他癌症治疗一样,pirtobrutinib可能会影响健康细胞和肿瘤细胞,这可能会导致副作用,这也将在本研究中进行研究。这项研究很活跃,目前正在招募新的患者,他们至少接受过一次MCL治疗,但从未接受过BTK抑制剂治疗。临床试验注册:NCT04662255(ClinicalTrials.gov)。
    Treatment with covalent Bruton tyrosine kinase inhibitors (BTKi) represents an important advance in the management of relapsed or refractory mantle cell lymphoma, but these treatments are not curative and many patients ultimately relapse. Pirtobrutinib, a highly selective, noncovalent (reversible) BTKi, inhibits both wild type and C481-mutant BTK with equal low nM potency, and has favorable oral pharmacology that enables continuous BTK inhibition throughout the dosing interval regardless of intrinsic rate of BTK turnover. Pirtobrutinib is well tolerated and has demonstrated promising efficacy in patients with poor prognosis B-cell malignancies following prior therapy, including covalent BTKi. This phase III, head-to-head, randomized study (NCT04662255) will evaluate whether pirtobrutinib is superior to investigator\'s choice of covalent BTKi in patients with previously treated, BTKi-naive mantle cell lymphoma.
    MCL is an uncommon type of B-cell non-Hodgkin lymphoma, a cancer of the immune system. It starts in the part of the lymph node called the mantle zone, where unusual B cells gather and crowd out healthy B cells in the lymph nodes, spleen, bone marrow and/or other organs. MCL can be caused by inappropriate cell signaling. BTK has been identified as a key driver of unusual cell signaling and blocking BTK has been shown to help kill the cancer cells. Covalent (not reversible) BTK inhibitors have advanced the treatment of MCL, but the effectiveness of these treatments is limited by side effects and treatment resistance. Pirtobrutinib, a noncovalent (reversible) BTK inhibitor, has been shown to have manageable side effects and to be effective in patients with MCL following previous treatment, including treatment with covalent BTK inhibitors. The BRUIN MCL-321 study compares pirtobrutinib with three currently approved covalent BTK inhibitors (ibrutinib, acalabrutinib or zanubrutinib), in patients with MCL who have never received any form of BTK inhibitor. This trial will look at how many people live with the disease without it getting worse. Like other cancer treatments, pirtobrutinib may affect both healthy cells and tumor cells, which can result in side effects that will also be looked at in this study. This study is active and currently recruiting new patients who have received at least one previous therapy for MCL and have never been treated with a BTK inhibitor. Clinical Trial Registration: NCT04662255 (ClinicalTrials.gov).
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  • 文章类型: Journal Article
    背景:很少报道CD10和BCL-6共表达的套细胞淋巴瘤(MCL),其生物学特征在很大程度上仍然未知。因此,这项研究旨在描述临床和生物学特征,以及CD10和BCL-6共表达的MCL患者的预后。
    方法:选取我院2011年1月至2018年10月收治的MCL患者104例。这些患者根据2016年世界卫生组织(WHO)的造血和淋巴组织肿瘤分类系统进行诊断,符合细胞形态学和免疫组织化学分析的结果。通过电话采访对患者进行了随访,医疗记录。年龄差异,性别,白细胞计数,乳酸脱氢酶(LDH)水平,分析β-2微球蛋白(β2-MG)水平及免疫组化结果。然后用Kaplan-Meier法和log-rank检验进行无事件生存率(EFS)和总生存率(OS)。
    结果:结果表明,总的来说,5例患者浅表淋巴结肿大,2例患者腹部不适,1例患者的红细胞(RBC)计数在诊断时异常。所有患者均处于IV期,75%有骨髓受累,75%和100%的患者LDH和β2-MG水平升高,分别。这8例患者涉及3个经典基因和5个变异。CD10和BCL-6共表达的MCL患者Ki-67指数较高,白细胞(WBC)计数,LDH水平,和β2-MG水平高于无CD10和BCL-6共表达的水平(P分别为0.025、0.038、0.015和0.021)。此外,CD10和BCL-6共表达的MCL患者的OS和EFS较短(χ2分别为6.401和5.975;P分别为0.011和0.015)。表明患者易患复杂核型和TP53异常。
    结论:CD10和BCL-6共表达的MCL患者更可能有骨髓受累,较高的Ki-67指数,白细胞计数增加,诊断时LDH和β2-MG水平升高,然后可能有复杂的细胞遗传学和不良预后。
    BACKGROUND: Mantle cell lymphoma (MCL) with co-expression of CD10 and BCL-6 was scarcely reported, and its biological features were largely remained unknown. Thus, this study aimed to describe the clinical and biological features, as well as outcome of MCL patients with co-expression of CD10 and BCL-6.
    METHODS: A total of 104 cases of MCL who were admitted to our hospital between January 2011 and October 2018 were recruited. Those patients were diagnosed according to the 2016 World Health Organization (WHO) classification system for tumors of the hematopoietic and lymphoid tissues, in compliance with the results of cytomorphology and immunohistochemical analysis. Patients were followed up through telephone interviews, medical records. Differences in age, gender, leukocyte count, lactate dehydrogenase (LDH) level, beta-2 microglobulin (β2-MG) level and results of immunohistochemistry were analyzed. Then the event-free survival (EFS) rate and overall survival (OS) rate were performed by the Kaplan-Meier method and log-rank test.
    RESULTS: The results showed that, in total, 5 patients had superficial lymph node enlargement, 2 patients suffered from abdominal discomfort, and 1 patient\'s red blood cell (RBC) count was abnormal at the time of diagnosis. All patients were in stage IV, 75% had bone marrow involvement, and 75% and 100% of patients had elevated levels of LDH and β2-MG, respectively. Three classic genes and five variants were involved in the 8 patients. MCL patients with the co-expression of CD10 and BCL-6 had higher Ki-67 index, white blood cell (WBC) count, LDH level, and β2-MG level than those of without co-expression of CD10 and BCL-6 (P=0.025, 0.038, 0.015, and 0.021, respectively). Besides, MCL patients with CD10 and BCL-6 co-expression had shorter OS and EFS (χ2=6.401 and 5.975; P=0.011 and 0.015, respectively), indicating patients\' susceptibility to get complex karyotype and TP53 abnormality.
    CONCLUSIONS: MCL patients with co-expression of CD10 and BCL-6 were more likely to have bone marrow involvement, higher Ki-67 index, increased WBC count, and elevated levels of LDH and β2-MG at the time of diagnosis, then might has complex cytogenetic and poor prognosis.
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