2014年12月10日讯 /生物谷BIOON/ --2014年第56届美国血液学会年会（ASH）于12月6日-9日在美国旧金山举行。近日，诺华（Novartis）在会上公布了深受业界期待的CAR-T免疫疗法CTL019的最新临床数据，在这些研究中，CTL019在某些类型淋巴细胞白血病表现出了巨大的治疗潜力。此次公布的一项长期儿科研究中，39例复发/难治（r/r）急性淋巴细胞白血病（ALL）儿科患者接受了CTL019的治疗，数据显示，有36例患者经历了完全缓解（CR），比例高达92%（n=36/39）。
儿科r/r ALL研究的其他亮点包括：平均随访时间为6个月；持续缓解长达1年或一年以上，6个月无事件存活率为70%，总存活率为75%。6个月CTL019持久性概率为68%并伴随B细胞发育不全（B cell aplasia），这是CTL019持久性和功能的一个药效学标志物。CTL019细胞的持久性可通过流式细胞仪和/或定量PCR检测，在持续缓解的患者中，伴随性B细胞发育不全在患者输注CTL019后可持续长达30个月。
诺华细胞和基因治疗单元全球主管Usman Azam表示，目前细胞治疗领域的技术创新日新月异，当我们看到儿科ALL患者输注CTL019后所取得的高达92%完全缓解率时，简直难以置信！我们将与宾夕法尼亚合作，扩大CTL019的临床患者覆盖范围。
接下来几天，诺华还将公布CTL019治疗B淋巴细胞癌（包括急性淋巴细胞白血病（ALL）、慢性淋巴细胞白血病（CLL）、B细胞非霍奇金淋巴瘤（NHL））一系列临床研究的惊人数据。
嵌合抗原受体-T细胞（CAR-T）疗法代表着当今最先进的肿瘤免疫细胞治疗技术，在该领域，诺华处于领先地位，其临床试验中有开发用于白血病、淋巴瘤、间皮瘤和胰腺癌的实验性产品。今年7月，FDA授予CAR-T免疫疗法CTL019突破性疗法认定。
不过，CAR-T领域的竞争也非常激烈，诺华主要竞争对手Juno开发的CAR-T免疫疗法JCAR015也收获了FDA的突破性疗法认定，近日Juno从美国国家癌症研究所（NCI）授权获得了一种互补性CAR-T产品，使该公司CAR-T管线资产达到了4个之多。该领域中，Kite制药、蓝鸟生物、新基（Celgene）也在迅速跟进。而制药巨头强生、葛兰素史克、辉瑞在今年通过授权合作纷纷进入CAR-T领域。
英文原文：Novartis highlights new CTL019 clinical data showing complete remissions in children and young adults with relapsed/refractory acute lymphoblastic leukemia
Data shows 36 of 39 pediatric patients with relapsed/refractory acute lymphoblastic leukemia (r/r ALL) (92%) experienced complete remissions
Additionally, sustained remissions were achieved up to one year or more with 6-month event-free survival of 70% and overall survival of 75%, in most cases without further therapy
Novartis and Penn have exclusive global collaboration to research, develop and commercialize CAR T cell therapies for the investigational treatment of cancers
Basel, Switzerland, December 6, 2014 - Findings from continued clinical studies of investigational chimeric antigen receptor (CAR) therapy, CTL019, demonstrate its potential role in the treatment of certain types of lymphocytic leukemia. In one long-term study of pediatric patients with acute lymphoblastic leukemia (ALL), results showed that 36 of 39 pediatric patients with relapsed/refractory (r/r) ALL, or 92%, experienced complete remissions (CR) with CTL019[1].
These results, which will be presented in an oral session at the 56th American Society of Hematology (ASH) annual meeting in San Francisco, continue to increase scientific understanding of CTL019 (Abstract #380, December 8, 10:45 AM)[1]. Additional abstracts will be presented at ASH that evaluate the efficacy and safety of CTL019 in the treatment of B cell cancers including ALL, chronic lymphocytic leukemia (CLL) and B cell non-Hodgkin lymphoma (NHL).
"We`re seeing pediatric patients who have not responded to any other therapy achieve complete remission as a result of treatment with CTL019," said lead investigator Stephan Grupp, MD, PhD, the Yetta Deitch Novotny Professor of Pediatrics at the Perelman School of Medicine at the University of Pennsylvania and director of Translational Research in the Center for Childhood Cancer Research at the Children`s Hospital of Philadelphia (CHOP). "However, this is only the first step. Now that these patients have been followed for a longer period of time, we`re seeing that a number of them remain in remission for one year or more. This leads me to believe the persistence and durability of CAR-modified cells may help protect against relapse."
Additional highlights of the pediatric r/r ALL study include findings that patients have ongoing CR. Median follow-up was 6 months. Sustained remissions were achieved up to one year or more with 6-month event-free survival of 70% and overall survival of 75%, in most cases without further therapy[1]. The probability of six-month CTL019 persistence was 68%, which was accompanied by B cell aplasia, a pharmacodynamic marker of CTL019 persistence and function[2]. Persistence of CTL019 cells detected by flow cytometry and/or qPCR, and accompanied by B cell aplasia, continued for up to 30 months after infusion in patients with ongoing responses[1].
All responding patients developed cytokine release syndrome (CRS) at peak T cell expansion. Treatment for CRS was required for hemodynamic or respiratory instability in 33% of patients and CRS was managed with an IL-6 receptor antagonist, together with corticosteroids in five patients. These events were delayed, and few patients experienced infusional toxicities, including infusion-associated fever[1].
"Innovation in the cellular therapy field is accelerating right now. When we see the response patients have to CTL019 when they have few options left, it`s incredibly inspiring," said Usman Azam, Global Head, Cell & Gene Therapies Unit, Novartis Pharmaceuticals. "Novartis will leverage our facility in Morris Plains, the first FDA-approved Good Manufacturing Practices quality site for a cell therapy, and the multi-center study for CTL019 in collaboration with the University of Pennsylvania, to broaden the reach of this therapy to additional patients in the clinical setting."
Also included among the presentations at ASH is a study investigating CTL019 in the treatment of individuals with CD19+ B cell lymphomas (Abstract #3087; December 7, 6:00 PM - 8:00 PM) that reveals complete responses in patients with advanced, relapsed or refractory diffuse large B-cell lymphoma and follicular lymphoma[3]. In addition, data will be presented on three cases of refractory cytokine release syndrome (CRS) in adult patients with ALL (Abstract #2296, December 7, 6:00 PM - 8:00 PM)[4]. CRS is correlated with CTL019 proliferation and the severity of CRS is correlated with disease burden[1],[2],[4].