小柯机器人

美国墨菲特癌症中心Bijal D Shah团队研究了KTE-X19治疗复发或难治性成人B细胞急性淋巴细胞白血病的疗效。该成果于2021年6月4日发表于《柳叶刀》杂志上。

尽管采用了新型疗法和异基因干细胞移植（allo-SCT）巩固治疗，复发或难治性前体B急性淋巴细胞白血病成人患者的预后仍然很差，这表明需要寻找更有效的疗法。

研究组进行了一项国际、多中心、单臂、开放标签研究，评估自体抗CD19嵌合抗原受体（CAR）T细胞疗法KTE-X19治疗复发或难治性前体B急性淋巴细胞白血病成人患者的有效性和安全性。在美国、加拿大和欧洲的25个机构招募年龄为18岁及以上，东部肿瘤合作组的表现状态为0-1，骨髓中存在形态学病变的患者。

在白细胞去除和条件化疗后，患者接受单次KTE-X19输注。主要终点是总体完全缓解率或中心评估的血液系统不完全恢复的完全缓解率。次要终点为缓解期和无复发生存期、总生存期、最小残留病（MRD）阴性率和allo-SCT率。对治疗人群（所有接受KTE-X19剂量的患者）进行疗效和安全性分析。

2018年10月1日至2019年10月9日，71名患者被纳入并接受了白细胞去除术。65例（92%）患者成功制备KTE-X19，55例（77%）接受给药。治疗患者的中位年龄为40岁。中位随访16.4个月后，39例（71%）患者达到完全缓解或伴血液系统恢复不完全的完全缓解，31例（56%）患者达到完全缓解。中位缓解持续时间为12.8个月，中位无复发生存期为11.6个月，中位总生存期为18.2个月。在未达到中位总生存期的缓解者中，38例（97%）患者MRD阴性。

10例（18%）患者在输注KTE-X19后接受allo-SCT巩固治疗。患者最常见的3级及以上不良事件是贫血（27例[49%]）和发热（20例[36%]患者）。14例（25%）患者出现3级及以上感染。2例患者发生5级KTE-X19相关事件（脑疝和脓毒性休克）。13例（24%）患者发生3级及以上细胞因子释放综合征，14例（25%）患者发生3级及以上神经事件。

研究结果表明，KTE-X19治疗复发或难治性前体B急性淋巴细胞白血病成人患者，显示出较高的完全缓解率或完全缓解伴不完全血液系统恢复，缓解患者中位总生存期未达到，且安全性可控。KTE-X19有望为这些患者带来长期的临床益处。

附：英文原文

Title: KTE-X19 for relapsed or refractory adult B-cell acute lymphoblastic leukaemia: phase 2 results of the single-arm, open-label, multicentre ZUMA-3 study

Author: Bijal D Shah, Armin Ghobadi, Olalekan O Oluwole, Aaron C Logan, Nicolas Boissel, Ryan D Cassaday, Thibaut Leguay, Michael R Bishop, Max S Topp, Dimitrios Tzachanis, Kristen M ODwyer, Martha L Arellano, Yi Lin, Maria R Baer, Gary J Schiller, Jae H Park, Marion Subklewe, Mehrdad Abedi, Monique C Minnema, William G Wierda, Daniel J DeAngelo, Patrick Stiff, Deepa Jeyakumar, Chaoling Feng, Jinghui Dong, Tong Shen, Francesca Milletti, John M Rossi, Remus Vezan, Behzad Kharabi Masouleh, Roch Houot

Issue&Volume: 2021-06-04

Abstract:

Background

Despite treatment with novel therapies and allogeneic stem-cell transplant (allo-SCT) consolidation, outcomes in adult patients with relapsed or refractory B-precursor acute lymphoblastic leukaemia remain poor, underlining the need for more effective therapies.

Methods

We report the pivotal phase 2 results of ZUMA-3, an international, multicentre, single-arm, open-label study evaluating the efficacy and safety of the autologous anti-CD19 chimeric antigen receptor (CAR) T-cell therapy KTE-X19 in adult patients with relapsed or refractory B-precursor acute lymphoblastic leukaemia. Patients were enrolled at 25 sites in the USA, Canada, and Europe. Eligible patients were aged 18 years or older, with Eastern Cooperative Oncology Group performance status of 0–1, and morphological disease in the bone marrow (>5% blasts). After leukapheresis and conditioning chemotherapy, patients received a single KTE-X19 infusion (1×106 CAR T cells per kg bodyweight). The primary endpoint was the rate of overall complete remission or complete remission with incomplete haematological recovery by central assessment. Duration of remission and relapse-free survival, overall survival, minimal residual disease (MRD) negativity rate, and allo-SCT rate were assessed as secondary endpoints. Efficacy and safety analyses were done in the treated population (all patients who received a dose of KTE-X19). This study is registered with ClinicalTrials.gov, NCT02614066.

Findings

Between Oct 1, 2018, and Oct 9, 2019, 71 patients were enrolled and underwent leukapheresis. KTE-X19 was successfully manufactured for 65 (92%) patients and administered to 55 (77%). The median age of treated patients was 40 years (IQR 28–52). At the median follow-up of 16·4 months (13·8–19·6), 39 patients (71%; 95% CI 57–82, p<0·0001) had complete remission or complete remission with incomplete haematological recovery, with 31 (56%) patients reaching complete remission. Median duration of remission was 12·8 months (95% CI 8·7–not estimable), median relapse-free survival was 11·6 months (2·7–15·5), and median overall survival was 18·2 months (15·9–not estimable). Among responders, the median overall survival was not reached, and 38 (97%) patients had MRD negativity. Ten (18%) patients received allo-SCT consolidation after KTE-X19 infusion. The most common adverse events of grade 3 or higher were anaemia (27 [49%] patients) and pyrexia (20 [36%] patients). 14 (25%) patients had infections of grade 3 or higher. Two grade 5 KTE-X19-related events occurred (brain herniation and septic shock). Cytokine release syndrome of grade 3 or higher occurred in 13 (24%) patients and neurological events of grade 3 or higher occurred in 14 (25%) patients.

Interpretation

KTE-X19 showed a high rate of complete remission or complete remission with incomplete haematological recovery in adult patients with relapsed or refractory B-precursor acute lymphoblastic leukaemia, with the median overall survival not reached in responding patients, and a manageable safety profile. These findings indicate that KTE-X19 has the potential to confer long-term clinical benefit to these patients.

DOI: 10.1016/S0140-6736(21)01222-8

Source: https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(21)01222-8/fulltext

LANCET：《柳叶刀》，创刊于1823年。隶属于爱思唯尔出版社，最新IF：202.731
官方网址：http://www.thelancet.com/
投稿链接：http://ees.elsevier.com/thelancet