2014年12月10日訊 /生物谷BIOON/ --2014年第56屆美國血液學會年會（ASH）於12月6日-9日在美國舊金山舉行。近日，諾華（Novartis）在會上公布了深受業界期待的CAR-T免疫療法CTL019的最新臨床數據，在這些研究中，CTL019在某些類型淋巴細胞白血病表現出了巨大的治療潛力。此次公布的一項長期兒科研究中，39例復發/難治（r/r）急性淋巴細胞白血病（ALL）兒科患者接受了CTL019的治療，數據顯示，有36例患者經歷了完全緩解（CR），比例高達92%（n=36/39）。(相關閱讀：小車（CAR-T）越滾越快；CAR-T領域新動作：諾華對手Juno牽手NCI擴充CAR-T資產)
兒科r/r ALL研究的其他亮點包括：平均隨訪時間為6個月；持續緩解長達1年或一年以上，6個月無事件存活率為70%，總存活率為75%。6個月CTL019持久性概率為68%並伴隨B細胞發育不全（B cell aplasia），這是CTL019持久性和功能的一個藥效學標誌物。CTL019細胞的持久性可通過流式細胞儀和/或定量PCR檢測，在持續緩解的患者中，伴隨性B細胞發育不全在患者輸注CTL019後可持續長達30個月。
諾華細胞和基因治療單元全球主管Usman Azam表示，目前細胞治療領域的技術創新日新月異，當我們看到兒科ALL患者輸注CTL019後所取得的高達92%完全緩解率時，簡直難以置信！我們將與賓夕法尼亞合作，擴大CTL019的臨床患者覆蓋範圍。
接下來幾天，諾華還將公布CTL019治療B淋巴細胞癌（包括急性淋巴細胞白血病（ALL）、慢性淋巴細胞白血病（CLL）、B細胞非霍奇金淋巴瘤（NHL））一系列臨床研究的驚人數據。
嵌合抗原受體-T細胞（CAR-T）療法代表著當今最先進的腫瘤免疫細胞治療技術，在該領域，諾華處於領先地位，其臨床試驗中有開發用於白血病、淋巴瘤、間皮瘤和胰腺癌的實驗性產品。今年7月，FDA授予CAR-T免疫療法CTL019突破性療法認定。
不過，CAR-T領域的競爭也非常激烈，諾華主要競爭對手Juno開發的CAR-T免疫療法JCAR015也收穫了FDA的突破性療法認定，近日Juno從美國國家癌症研究所（NCI）授權獲得了一種互補性CAR-T產品，使該公司CAR-T管線資產達到了4個之多。該領域中，Kite製藥、藍鳥生物、新基（Celgene）也在迅速跟進。而製藥巨頭強生、葛蘭素史克、輝瑞在今年通過授權合作紛紛進入CAR-T領域。（生物谷Bioon.com）
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].