BTK inhibitors

BTK 抑制剂
  • 文章类型: Journal Article
    患有淋巴增殖性疾病(LPD)的老年患者容易受到严重急性呼吸综合征冠状病毒2(SARS-CoV-2)感染。这里,我们回顾性分析了2022年11月至2023年4月在中国江苏省淋巴瘤协作组(JCLG)招募的364例老年淋巴瘤患者中OmicronSARS-CoV-2首次感染的临床特征和结局.中位年龄为69岁(范围60-92)。54.4%(198/364)的患者被确认为严重和危重的COVID-19感染。在单变量分析中,年龄>70岁(OR1.88,p=0.003),具有多种合并症(OR1.41,p=0.005),侵袭性淋巴瘤(OR2.33,p<0.001),活动性疾病(进行性或复发性/难治性,OR2.02,p<0.001),积极的抗淋巴瘤治疗(OR1.90,p<0.001)与严重的COVID-19相关。在多变量分析中,先前抗淋巴瘤治疗的多个(三个或更多个)系列(OR3.84,p=0.021)仍然是严重COVID-19的不利因素。此外,过去6个月内基于CD20抗体(利妥昔单抗或奥比妥珠单抗)的治疗与整个队列中的严重COVID-19相关(OR3.42,p<0.001)。在惰性淋巴瘤队列中,连续BTK抑制剂可能对COVID-19感染的预后有保护作用(OR0.44,p=0.043)。总的来说,7.7%(28/364)的患者停止治疗,之前的多线抗淋巴瘤治疗(OR3.46,p=0.016)仍然是死亡率的不良因素.
    Elderly patients with lymphoproliferative diseases (LPD) are vulnerable to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Here, we retrospectively described the clinical features and outcomes of the first time infection of Omicron SARS-CoV-2 in 364 elderly patients with lymphoma enrolled in Jiangsu Cooperative Lymphoma Group (JCLG) between November 2022 and April 2023 in China. Median age was 69 years (range 60-92). 54.4% (198/364) of patients were confirmed as severe and critical COVID-19 infection. In univariable analysis, Age > 70 years (OR 1.88, p = 0.003), with multiple comorbidities (OR 1.41, p = 0.005), aggressive lymphoma (OR 2.33, p < 0.001), active disease (progressive or relapsed/refractory, OR 2.02, p < 0.001), and active anti-lymphoma therapy (OR 1.90, p < 0.001) were associated with severe COVID-19. Multiple (three or more) lines of previous anti-lymphoma therapy (OR 3.84, p = 0.021) remained an adverse factor for severe COVID-19 in multivariable analysis. Moreover, CD20 antibody (Rituximab or Obinutuzumab)-based treatments within the last 6 months was associated with severe COVID-19 in the entire cohort (OR 3.42, p < 0.001). Continuous BTK inhibitors might be protective effect on the outcome of COVID-19 infection (OR 0.44, p = 0.043) in the indolent lymphoma cohort. Overall, 7.7% (28/364) of the patients ceased, multiple lines of previous anti-lymphoma therapy (OR 3.46, p = 0.016) remained an adverse factor for mortality.
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  • 文章类型: Observational Study
    背景:慢性淋巴细胞白血病(CLL)和其他非霍奇金淋巴瘤(NHL)导致广泛的免疫抑制,赋予SARS-CoV-2发病率和死亡率更大的风险。我们的研究分析了这些癌症患者SARS-CoV-2疫苗接种的抗体(Ab)血清阳性。
    方法:最终分析,240名患者参与其中,和血清阳性定义为阳性的总或尖峰蛋白Ab。
    结果:CLL中血清阳性为50%,68%的WM,其余的NHL占70%。在所有癌症中,与辉瑞疫苗接种相比,Moderna疫苗接种导致更高的血清阳性(64%vs.49%;P=0.022),特别是CLL患者(59%vs.43%;P=0.029)。这种差异不能通过治疗状态或先前的抗CD20单克隆Ab治疗的差异来解释。在CLL患者中,与未接受治疗的患者相比,目前或之前的癌症治疗导致较低的血清阳性(36%vs.68%;P=.000019)。与辉瑞相比,接受布鲁顿酪氨酸激酶(BTK)抑制剂治疗的CLL患者在接受Moderna疫苗接种后具有更好的血清阳性(50%vs.23%;P=.015)。在所有癌症中,与超过一年相比,1年内的抗CD20药物导致较低的Ab反应(13%vs.40%;P=.022),加强疫苗接种后仍然存在差异。
    结论:无痛性淋巴瘤患者的抗体反应低于一般人群。在有抗白血病药物治疗史或用辉瑞疫苗免疫的患者中发现较低的Ab血清阳性。该数据表明,Moderna疫苗接种可能会在惰性淋巴瘤患者中对SARS-CoV-2产生更大程度的免疫力。
    Chronic lymphocytic leukemia (CLL) and other non-Hodgkin\'s lymphomas (NHLs) lead to broad immunosuppression, conferring a greater risk for morbidity and mortality from SARS-CoV-2. Our study analyzed antibody (Ab) seropositivity from SARS-CoV-2 vaccination in patients with these cancers.
    In the final analysis, 240 patients were involved, and seropositivity was defined as a positive total or spike protein Ab.
    Seropositivity was 50% in CLL, 68% in WM, and 70% in the remaining NHLs. Moderna vaccination led to higher seropositivity compared to Pfizer vaccination across all cancers (64% vs. 49%; P = .022) and specifically CLL patients (59% vs. 43%; P = .029). This difference was not explainable by differences in treatment status or prior anti-CD20 monoclonal Ab therapy. In CLL patients, current or prior cancer therapy led to lower seropositivity compared to treatment-naïve patients (36% vs. 68%; P = .000019). CLL patients treated with Bruton\'s tyrosine kinase (BTK) inhibitors had better seropositivity after receiving the Moderna vaccination compared to Pfizer (50% vs. 23%; P = .015). Across all cancers, anti-CD20 agents within 1 year led to a lower Ab response compared to greater than one year (13% vs. 40%; P = .022), a difference which persisted after booster vaccination.
    Antibody response is lower in patients with indolent lymphomas compared to the general population. Lower Ab seropositivity was found in patients with a history of anti-leukemic agent therapy or those immunized with Pfizer vaccine. This data suggests that Moderna vaccination may confer a greater degree of immunity against SARS-CoV-2 in patients with indolent lymphomas.
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  • 文章类型: Journal Article
    在本文中,提出了基于LQTA-QSAR方法和MIA-QSAR分析的4D-QSAR分析。建立了具有较好预测性能的4D-QSAR模型和MIA-QSAR模型的组合模型。4D-QSAR描述符是通过计算探针之间的相互作用能和分子动力学模拟产生的对齐构象集合曲线(CEP)获得的。从化学结构的对齐图像生成MIA描述符。这些描述符被过滤并用于偏最小二乘(PLS)回归。通过合并4D-QSAR和MIA-QSAR两种分析方法生成的描述符,建立了组合模型。这些模型是使用作者编写的程序构建的,任何人都可以在https://github.com/masgils下载这些程序。
    In this paper, 4D-QSAR analysis base on LQTA-QSAR method and MIA-QSAR analysis were presented. And a combination model of 4D-QSAR model and MIA-QSAR model with better predictive performance was built. The 4D-QSAR descriptors were obtained by calculating the interaction energies between the probes and aligned conformational ensemble profiles (CEP) resulting from molecular dynamics simulation. The MIA descriptors were generated from aligned images of chemical structure. Those descriptors were filtered and employed in partial least squares (PLS) regression. The combination model was built by the merging the descriptors generated by the two methods of 4D-QSAR and MIA-QSAR analysis. Those models were built using programs written by authors, and anyone can download those programs at https://github.com/masgils.
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  • 文章类型: Clinical Trial, Phase I
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