Phase 2 CAR-T study reports significant remission rates at 15-month follow up

MD安德森News Release December 10, 2017

一个studyinvolving the recently approved CD19-targeting chimeric antigen receptor (CAR) T cell therapy shows that 42 percent of patients with aggressive large B-cell lymphoma remained in remission at 15 months following treatment with axi-cel (marketed as Yescarta™).

The study, named ZUMA-1, also reported measurable responses in 82 percent of patients and complete responses in 54 percent. Fifty-six percent were alive at 15 months following therapy, with some remaining cancer free two years post-treatment.

The findings, reported in the Dec. 10 online issue of新英格兰医学杂志，并在的年会上提交12月11日一个merican Society of Hematology（ASH）在亚特兰大，源于为首的22机构研究有情Neelapu, M.D.，教授Lymphoma & Myeloma在The University of Texas MD Anderson Cancer CenterandFrederick Locke医学博士，副主席，血液和骨髓移植和细胞免疫治疗在莫菲特癌症中心部的会员。

“With the FDA’s recent approval of this therapy, we believe this is a major advance in the treatment of patients with relapsed or refractory large B-cell lymphoma and is likely to save or prolong lives of many patients,” said Neelapu. “This study demonstrated that axi-cel provides remarkable improvement in outcomes over existing therapies for these patients who have no curative options.”

The study, which began in April 2015, administered axi-cel to 108 patients who had failed prior chemotherapy and autologous stem cell transplantation. In some cases, the patients who had received chemotherapy were too far progressed to undergo stem cell transplantation and were placed on the trial following chemotherapy. The patients’ T-cells were extracted through a process called leukapheresis and genetically reengineered with CAR molecules that help T-cells attack cancer cells. The reengineered T cells are infused back into the patient.

“This is the first FDA-approved gene therapy to treat adult lymphoma. Axi-cel consists of the patients’ own T cells that have been reprogrammed, and then reinfused to detect and destroy lymphoma. Many patients’ lymphoma tumors melted away within a month. The long term follow-up results of the ZUMA-1 trial show that axi-cel remissions can last years, and these are patients that did not respond to chemotherapy,” said Locke.

患者最完整的答复弥漫性大B细胞淋巴瘤（最常见的侵袭性非霍奇金淋巴瘤），原发性纵隔B细胞淋巴瘤和转化滤泡性淋巴瘤，发生由治疗的第一个月，虽然有些报道晚到一个一年了，从治疗。持续持久的缓解已经在患者中观察到2年后的治疗。而调查正在进行，对治疗的抗性中的一个机制似乎是由于在肿瘤细胞中的CD19靶的损失。理解性的这些机制预计将导致新的方法发展，进一步增强该疗法的疗效。

一个bout the study patients
The drug was manufactured for 99 percent of the 108 study participants and given to 91 percent of enrolled patients. On average, it took 17 days from the time T-cells were harvested from the patient to when the drug was administered, a relatively quick turnaround time for patients with a rapidly growing disease such as large B-cell lymphoma.

在与AXI-CEL治疗的患者，中位年龄为58，从23到76岁。患者八五％的III期或IV期疾病。该研究还报道了之前接收为轴CEL，患者的77％继续有以下二线或更高的治疗侵袭性疾病进展，和21％的人干细胞移植后疾病复发。患者至少有69％接受至少三个先前治疗，26％有原发性难治性疾病史。

所有108例患者经历了一些不利的影响，虽然不是所有有联系的AXI-CEL具有95级3项％的活动，包括发热，低白细胞和血小板计数，和贫血。细胞因子释放综合征，炎症反应的一种形式，发生率为93％，但大多数是低档。患者大约有64％经历过神经系统事件，包括脑病，一般的混乱和说话困难，这通常发生五天左右到治疗，两周内解决。

该研究报告的相关不良反应包括三名病人死亡。其中两名病人有细胞因子释放综合征，由于AXI-CEL，和一个经历了肺栓塞被认为无关的AXI-CEL。这些死亡发生在研究和响应过程的早期，额外的安全准则，在所有22位研究采用以确保一致的监督和不良反应及时管理。研究观察到，CAR-T水平的患者的血液系统达到峰值的14天内和输注后的180天呈在大多数患者中检测到。谁在2年后的治疗停留在完全缓解三名病人继续有检测CAR-T的水平。

Only treatment centers certified to provide stem cell transplantation are eligible to be considered as axi-cel treatment sites. The drug’s manufacturer, Kite Pharma, a Gilead company, ultimately anticipates certifying up to 90 centers across the U.S. Physicians must undergo special training and follow stringent guidelines and procedures before administering the new therapy.

一个t MD Anderson, the study also included participation by Jason Westin, M.D., Department of Lymphoma & Myeloma. Other participating institutions included Moffitt Cancer Center, Tampa, Fla.; Washington University, St. Louis; University of Miami; Stanford University; Dana-Farber Cancer Institute, Boston; Montefiore Medical Center, New York; Vanderbilt University Medical Center, Nashville, Tenn.; City of Hope National Medical Center, Duarte, CA; Mayo Clinic, Rochester, Minn.; University of California at Los Angeles; Loyola University of Rochester School of Medicine, Rochester, N.Y.; Sarah Cannon Research Institute, Nashville; John Theurer Cancer Center, Hackensack, N.J.; Cleveland Clinic; Karmanos Cancer Center, Wayne State University, Detroit; University of Iowa Carver College of Medicine, Iowa City, Iowa; Colorado Blood Cancer Institute, Denver; Banner MD Anderson Cancer Center, Gilbert, Ariz.; Tel-Aviv Sourasky Medical Center, Tel Aviv; University of California at San Diego; and Kite Pharma, Santa Monica, Calif.

The study was funded by Kite Pharma and in part by the Leukemia & Lymphoma Society Therapy Acceleration Program. Neelapu serves as a scientific advisory board member and Locke is a scientific advisory for Kite.