依鲁替尼和TGR-1202联合治疗白血病和淋巴瘤效果惊人

两种靶向药物的联用（其中一种药物依鲁替尼已获美国食品药品监督管理局（FDA）批准，而另外一种药物正在试验中）已在复发或难治性慢性淋巴细胞性白血病（CLL）或套细胞淋巴瘤（MCL）患者的1期试验中证明了其安全性和有效性。丹娜法伯癌症研究所的研究员将在第58届美国血液学协会（ASH）的年会上报告这项研究成果。

本试验通过血液癌症研究Partnership,以及由美国白血病淋巴瘤协会资助的丹娜法伯血液恶性肿瘤研究学会入组一定数量的CLL患者，其余由MCL患者补充，而且该项研究在其他几个机构也是开放的。丹娜法伯研究员将从以下两个方面进行研究。

其一，患者联合使用已获批的药物依鲁替尼和正在试验中的新型药物TGR-1202以确定二者是否可以同时安全服用；其二，与单使用依鲁替尼相比较，两药物联用是否使CLL和MCL患者获得更长时间的完全消退。

虽然依鲁替尼靶向作用于细胞蛋白BTK，而且常常降低复发或耐药CLL或MCL患者的癌症数量，但是在消除癌症或在治疗MCL或高风险CLL方面几乎不能产生长久的治疗效果。通过阻断P13K-delta蛋白的TGR-1202与依鲁替尼的配对结合，研究者希望能使癌症细胞生长周期中重要的两部分失活。

   截止7月末，研究者已使用上述两种药物联合疗法治疗28名患者，其中包括17名CLL患者，11名CLL患者。实验方案结果显示安全，同时也发现800mg剂量的TGR-1202适用于进一步研究。

   丹娜法伯Mattew David，研究者发起试验的主要研究者，说到“两药物联合应用获得可喜的治疗效果。”David将在12月5日圣地亚哥会议中心展示研究成果。David还补充说到“研究过程中已发现有一名CLL患者完全消退，没有癌症迹象，其他几名患者也接近完全消退。”

   David还指出：“两种药物联用的另一个潜在优势是其能在治疗中提供较大的灵活性”。因暂时出现的并发症需停用任意一种药物的患者可继续服用另一种药物，而当并发症消失时，可以继续采用两种药物治疗方案。（丹娜法伯癌症研究院 麻省医疗国际郭娜）

Drug combination yields encouraging results in patients with relapsed forms of leukemia or lymphoma in early stage study Share

Matthew Davids, MD

A combination of two targeted agents – one approved by the Food and Drug Administration and one undergoing testing – has demonstrated safety as well as encouraging signs of effectiveness in a phase 1 clinical trial in patients with relapsed or hard-to-treat chronic lymphocytic leukemia (CLL) or mantle cell lymphoma (MCL). Dana-Farber Cancer Institute researchers will report the findings at the 58th annual meeting of the American Society of Hematology (ASH).

The combination of the approved drug ibrutinib and the novel agent TGR-1202 is being tested in patients to determine if the two agents can be safely given at the same time and whether they lead to more durable remissions in CLL and MCL compared to ibrutinib alone. While ibrutinib, which targets the cell protein BTK, often reduces the amount of cancer in patients with relapsed or drug-resistant CLL or MCL, it rarely eliminates the cancer or generates long-lasting results in MCL or high-risk forms of CLL. By pairing it with TGR-1202, which blocks the P13K-delta protein, researchers hope to disable two key parts of cancer cells’ growth circuitry.

As of late July, investigators had treated 28 patients – 17 with CLL, 11 with MCL – with the tandem therapy. The regimen was shown to be safe, with an 800 mg dose of TGR-1202 found to be suitable for further study.

“The efficacy of the combination looks promising as well,” said Dana-Farber’s Matthew Davids, MD, principal investigator of the investigator-initiated trial. Davids will present the findings Monday, December 5, at 8 a.m. in Room 5AB of the San Diego Convention Center. “We have already seen a complete response – no evidence of cancer – in one patient with CLL, and several other patients are approaching complete response,” Davids added.

Another potential benefit of the two-drug combination is that it could offer greater flexibility in treatment, Davids remarked. Patients who need to discontinue one of the drugs because of temporary complications could continue with the other and resume the two-drug regimen when the complications subside.

While enrollment of patients with CLL in the trial is complete, openings remain for patients with MCL, and the study is open at several sites across the country through the Blood Cancer Research Partnership, a Dana-Farber-led hematologic malignancies research consortium funded through the Leukemia & Lymphoma Society.