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NEJM:Acalabrutinib有望治疗慢性淋巴细胞白血病(CLL)患者

2016-01-05 徐媛 MedSci原创

慢性淋巴细胞白血病(CLL)是一种原发于造血组织的恶性肿瘤。肿瘤细胞为单克隆的B淋巴细胞,形态类似正常成熟的小淋巴细胞,蓄积于血液、骨髓及淋巴组织中。 布鲁顿酪氨酸激酶(BTK)抑制剂依鲁替尼具有不可逆抑制的作用,这种不可逆抑制的作用对慢性淋巴细胞白血病(CLL)治疗具有促进作用。然而,依鲁替尼同时也不可逆地抑制了其他激酶靶点治疗,可能会削弱治疗效果。Acalabrutinib(ACP-19

慢性淋巴细胞白血病(CLL)是一种原发于造血组织的恶性肿瘤。肿瘤细胞为单克隆的B淋巴细胞,形态类似正常成熟的小淋巴细胞,蓄积于血液、骨髓及淋巴组织中。

布鲁顿酪氨酸激酶(BTK)抑制剂依鲁替尼具有不可逆抑制的作用,这种不可逆抑制的作用对慢性淋巴细胞白血病(CLL)治疗具有促进作用。然而,依鲁替尼同时也不可逆地抑制了其他激酶靶点治疗,可能会削弱治疗效果。Acalabrutinib(ACP-196)是一种更具有选择性的不可逆BTK抑制剂,主要为改善一代BTK抑制剂的安全性和有效性而设计。

在这项非对照性、1–2期多中心研究中,研究人员对61名复发性CLL患者进行口服acalabrutinib的安全性、有效性、药代动力学及药效学评估。在剂量递增阶段,患者接受acalabrutinib治疗100-400 mg/次,每日一次;当剂量扩增到第二期则给予acalabrutinib治疗100 mg/次,每日2次。

研究结果,研究人员收纳的患者平均年龄为62岁,在进行平均3种治疗方案治疗的复发性CLL患者中,有31%存在17p13.1缺失,75%的免疫球蛋白重链可变基因未突变。在剂量递增阶段未发生毒副作用。最常见的不良事件为头痛(占比43%),腹泻(占比39%)以及体重增加(占比26%)。大多数不良事件是1级或2级。在平均随访14.3个月后,总缓解率为95%,剩下的5%的患者病情稳定。伴17p13.1缺失的患者,总缓解率为100%。没有发现Richter综合征,只有一个患者在慢性淋巴细胞白血病进展的情况下发生。

在这项研究中,acalabrutinib对慢性淋巴细胞白血病(CLL)患者,包括那些伴17p13.1缺失的患者的治疗具有安全性和有效性。

原始出处

Byrd JC1, Harrington B, O'Brien S, Jones JA, Schuh A, Devereux S, Chaves J, Wierda WG, Awan FT, Brown JR, Hillmen P, Stephens DM, Ghia P, Barrientos JC, Pagel JM, Woyach J, Johnson D, Huang J, Wang X, Kaptein A, Lannutti BJ, Covey T, Fardis M, McGreivy J, Hamdy A, Rothbaum W, Izumi R, Diacovo TG, Johnson AJ, Furman RR.Acalabrutinib (ACP-196) in Relapsed Chronic Lymphocytic Leukemia.N Engl J Med. 2015 Dec 7.

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    2016-02-18 lishizhe
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目的:Ibrutinib导致慢性淋巴细胞白血病(CLL)患者瞬态淋巴球增多,这发生于药物开始的几小时内,是因为从淋巴组织进入血液中有细胞流出。因此,我们试图探讨ibrutinib对体内慢性淋巴细胞白血病细胞迁移和粘附的影响。实验设计:在研究-起始的II期试验阶段,患者接受单一剂量ibrutinib(420毫克每天)。收集预处理的和治疗期间来自体内的功能分析的连续血液样本。结果:慢性淋巴细胞白血病细

诺华白血病药物Arzerra III期临床显著改善复发性CLL无进展生存期

医药行业两大巨头诺华(Novartis)与葛兰素史克(GSK)价值220亿美元的资产置换交易于今年3月初圆满完成。其中,诺华以160亿美元收购葛兰素史克的肿瘤业务,使其在全球肿瘤治疗领域上升到了第二的位置,地位仅次于肿瘤学巨头罗氏(Roche)。近日,诺华公布了该笔交易中的白血病药物Arzerra(ofatumumab)一项III期COMPLEMENT-2研究的数据。该研究在复发性慢性淋巴细胞白血

2010年中国慢性淋巴细胞白血病诊断与治疗专家共识

近十几年来,国际上在慢性淋巴细胞白血病(CLL)基础研究、新的预后标志、诊断标准及治疗选择方面都取得了巨大进展,我国对CLL的研究也取得较大进展,但与国外研究差距较大,需要进一步规范临床诊断与治疗,促使我们制订中国CLL诊断与治疗专家共识,以促进我国各级血液科医生提高CLL及相关慢性B淋巴细胞增殖性疾病(B—LPD)的诊断和鉴别诊断水平,规范CLL的治疗。CLL是一种B淋巴细胞克隆性增殖的肿瘤性疾

Lancet Oncol:Ofatumumab维持治疗慢性淋巴细胞白血病效果

Ofatumumab是人类抗CD20单克隆抗体,其已经被证明在单一治疗难治慢性淋巴细胞白血病方面有疗效。研究人员评估了对于慢性淋巴细胞白血病复发再诱导治疗后的患者,ofatumumab进行维持治疗 vs 观察的安全性和疗效性。在这个开放性,多中心,随机3期研究中,招募的患者年龄在18岁或以上,来自24个国家130中心,这些患者都患有慢性淋巴细胞性白血病并在曾在二线或三线治疗后完全或部分缓解。符合条

GSK单抗药Arzerra III期显著改善复发性CLL无进展生存期

葛兰素史克(GSK)和合作伙伴Genmab制药7月31日宣布,独立数据监测委员会(IDMC)针对抗癌药Arzerra(ofatumumab)一项关键性III期PROLONG研究(OMB 112517)进行的一项既定中期分析表明,该项研究达到了改善疾病无进展生存期(PFS)的主要终点。该项研究在复发性慢性淋巴细胞白血病(CLL)患者中开展,评估了Arzerra维持疗法与未进一步治疗(观察)的差异。该

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