替代化疗？

A newly approved drug for the treatment of chronic lymphocytic leukemia (CLL), studied in clinical trials at MD Anderson, is showing significant promise. In February, the U.S. Food and Drug Administration granted accelerated approval of Imbruvica, for use in previously treated CLL patients.

“Ibrutinib产生持久的反应患者after other treatments have failed, and with very little toxicity. The main side effect is mild diarrhea that usually resolves over time," says Susan O'Brien, M.D., a professor in Leukemia who led the phase I clinical trial of the drug.

O’Brien and her MD Anderson colleagues were instrumental in bringing the drug, developed by Pharmacyclics, Inc., to clinical trial and helped solve a puzzle about ibrutinib’s initial effects, which appeared to be alarming. Today they continue advanced clinical trials, including a combination trial through MD Anderson’s Moon Shots Program.

"This is an exciting time for CLL, with ibrutinib and other drugs in clinical trials providing new approaches that move us away from reliance on chemotherapy combinations," O’Brien says. One important advantage is that ibrutinib does not suppress bone marrow production of normal blood cells such as red cells, platelets and infection-fighting white cells. CLL already does that, exposing patients to potentially lethal infections and to bleeding. Chemotherapy also can worsen this effect, known as myelosuppression.

Even successful drug regimens such as the fludarabine-cyclophosphamide-rituximab (FCR) combination, developed at MD Anderson and now considered the CLL standard of care, can be difficult for older patients to tolerate. Chemotherapy also raises a patient’s risk of developing other cancers later on.

“我们现在的目标是消除在治疗CLL化疗的需要，说：”迈克尔·基廷，医学博士，教授，白血病。

依罗替尼块布鲁顿酪氨酸激酶（BTK），B细胞受体信号传导的重要组成部分。在这样做时，它破坏了许多对于CLL细胞的存活和生长的重要分子信号的网络。

高响应率，阻碍疾病进展

In December, O’Brien reported on a clinical trial involving 140 CLL patients that showed ibrutinib alone produces complete or partial responses in 88% of patients who have had previous treatment, and 86% of those who have received the drug as initial therapy. At the 30-month mark, 76% remained on the drug and showed no sign of the disease progressing.

组合药物与抗体利妥昔单抗升压后的反应率95％在临床试验中为首扬汉堡，医学博士，在白血病副教授。在18个月内，有40患者组的78％，表现出没有进展。

驾驶CLL细胞从躲藏处出来

CLL发展缓慢，往往是几年前监控高白细胞计数等指标指向需要治疗。

令人担忧的是，谁在I期临床试验早期参加试验的患者服用表现依罗替尼后，增加了他们的白细胞计数。“这是正常疾病进展的一个标志，会导致患者被带下药物，”奥布莱恩说。

But there were offsetting clinical observations that discouraged jumping to conclusions.

“CLL细胞积聚在淋巴结，故这类病人有很多肿胀，尤其是在脖子上，”奥布莱恩说。正如白细胞计数上升，臃肿的淋巴结开始撤退和患者报告感觉好多了。最终，白数开始回落。

汉堡进行该照明发生了什么事情的实验室研究。

“依罗替尼冲白血病细胞从骨髓，淋巴结和脾脏进入它们失去它们从周围组织获取和慢慢死去的支持下，血液中的，”伯格说。“CLL细胞一般寿命长，即使没有存活的信号。”

快速反应

它可以采取血细胞计数和骨髓受累个月才能恢复正常所造成的依罗替尼中断生长信号慢慢的伤亡事故。谁在他们的CLL细胞缺乏某种基因突变有些患者反应更为迅速。

CLL登月推进事业

So far, ibrutinib has led to few complete remissions. The drug tamps down CLL, but so far doesn’t cure it, Burger reports. However, complete response rates are increasing in the group of patients taking the ibrutinib/rituximab combination. O’Brien suspects that, over time, more complete remissions will emerge as the ibrutinib slowly destroys CLL cells and patients are followed longer.

新药正在酝酿中。Idelalisib块不同的分子途径称为PI3K。奥布莱恩联合牵头药物利妥昔单抗联合的临床试验中，美罗华独自一人，为严重预处理CLL患者谁没有资格获得联合化疗相比。

结合得如此出众的临床试验早期的数据分析后，在十月停止。

CLL被选为MD安德森的登月一个，一个方案，以显着降低癌症死亡，开始有六个努力这一目标8种癌症。汉堡导致在十二月推出的新组合试验，比较依罗替尼对依罗替尼加上利妥昔单抗在208名以前治疗CLL患者。

Genomic analyses of patients’ CLL cells will be done before and during treatment and at the point of resistance, when it develops, to reveal how the disease changes during treatment.

汉堡和他的同事试图通过研究，其中白血病成为耐依罗替尼的情况下保持领先CLL的。“我们需要识别和理解这些机制，使我们能够开发方式，因为它产生战胜的阻力。”