Introduction

Outcomes with salvage regimens in pts with MCL who progress after Bruton tyrosine kinase inhibitor (BTKi) therapy are poor. ZUMA-2 is a Phase 2, registrational, multicenter study evaluating KTE-X19, an autologous anti-CD19 CAR T cell therapy, in pts with R/R MCL (1-5 therapies, including a BTKi). We present interim efficacy and safety results.

Objectives

Evaluate efficacy and safety of KTE-X19 in R/R MCL.

Methods

Eligible pts (≥ 18 y) with R/R MCL had an ECOG of 0-1 and ≤ 5 prior therapies, including chemotherapy, an anti-CD20 antibody, and a BTKi. Pts underwent leukapheresis and conditioning chemotherapy followed by KTE-X19 infusion at 2 × 10⁶ cells/kg. Bridging therapy with dexamethasone, ibrutinib, or acalabrutinib was permitted. The primary endpoint was objective response rate (ORR; complete response [CR] + partial response) assessed by an Independent Review Committee per the Lugano Classification (Cheson, et al. J Clin Oncol. 2014). Interim efficacy endpoints were investigator-assessed using the revised IWG Response Criteria for Malignant Lymphoma (Cheson, et al. J Clin Oncol. 2007). Key secondary endpoints were duration of response (DOR), progression-free survival (PFS), overall survival (OS), frequency of adverse events (AEs), and blood levels of CAR T cells and cytokines. Sixty pts received KTE-X19; here, we present results in pts with ≥ 1 y follow-up. Updated results in all 60 pts will be reported in the presentation.

Results

As of May 30, 2018, 28 pts received KTE-X19 with ≥ 1 y follow-up (median, 13.2 mo). The median age was 65 y; 43% of pts had an ECOG score of 1; 21% had blastoid morphology; 82% had stage IV disease; 50% had intermediate/high-risk MIPI; and 86% received a median of 4 prior therapies. In 20 of 28 pts with available data, the median Ki-67 index was 38%. Eight pts received bridging therapy; all had disease present post-bridging. Investigator-assessed ORR was 86% (95% CI, 67-96) with a CR rate of 57% (95% CI, 37-76). As of May 30, 2018, 75% of responders remained in response, and 64% of treated pts had ongoing responses. The 12-month rates of DOR, PFS, and OS were 83% (95% CI, 60-93), 71% (95% CI, 50-84), and 86% (95% CI, 66-94), respectively; medians were not reached. The most common Grade ≥ 3 AEs were anemia (54%), platelet count decreased (39%), and neutropenia (36%). Grade 3/4 cytokine release syndrome (CRS) assessed by Lee et al. (Blood. 2014) and Grade 3/4 neurologic events (NE) occurred in 18% and 46% of pts, respectively, with no Grade 5 events. CRS and NE were generally reversible. There was 1 Grade 5 AE of organizing pneumonia. Median CAR T cell levels measured by peak and area under the curve were 99 cells/µL (range, 0.4-2589) and 1542 cells/µL (range, 5.5-27239), respectively.

Conclusion

With ≥ 1 y follow-up, KTE-X19 demonstrated significant and durable clinical benefit, with a manageable safety profile in pts with R/R MCL for whom there are no curative treatment options.

中文翻译：

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KTE-X19，一种抗CD19嵌合抗原受体（CAR）T细胞疗法，用于复发/难治性套细胞淋巴瘤（R / R MCL）患者（Pts）：ZUMA-2 2期研究的结果

介绍

在布鲁顿酪氨酸激酶抑制剂（BTKi）治疗后进展为MCL的患者中，挽救方案的结果较差。ZUMA-2是一项2期注册，多中心研究，评估了KTE-X19（一种自体抗CD19 CAR T细胞疗法）在R / R MCL（1-5种疗法，包括BTKi）中的应用。我们提供中期疗效和安全性结果。

目标

评估KTE-X19在R / R MCL中的功效和安全性。

方法

符合条件的R / R MCL患者（≥18年）的ECOG为0-1，而先前的疗法包括化疗，抗CD20抗体和BTKi≤5。对患者进行白细胞分离和条件化疗，然后以2×10 ⁶细胞/ kg的剂量输注KTE-X19 。允许使用地塞米松，依鲁替尼或acalabrutinib进行桥接治疗。主要终点是根据卢加诺分类（Cheson等人，J Clin Oncol。2014）由独立审查委员会评估的客观缓解率（ORR；完全缓解[CR] +部分缓解）。研究者使用修订的IWG恶性淋巴瘤缓解标准对中期疗效终点进行了研究者评估（Cheson等，J Clin Oncol。2007）。主要的次要终点是反应持续时间（DOR），无进展生存期（PFS），总生存期（OS），不良事件发生率（AEs）以及CAR T细胞和细胞因子的血液水平。60例获得了KTE-X19；在这里，我们以≥1 y的随访时间给出结果。演示中将报告所有60分的最新结果。

结果

截至2018年5月30日，有28名患者接受了KTE-X19≥1年的随访（中位数为13.2 mo）。中位年龄为65岁；43％的患者的ECOG得分为1；21％具有胚泡形态；82％患有IV期疾病；50％的患者患有中/高危MIPI；有86％的人接受过4次中位治疗。在可获得数据的28分中，有20分中，Ki-67指数中位数为38％。八名患者接受了桥接治疗；桥接后都出现疾病。研究者评估的ORR为86％（95％CI，67-96），CR率为57％（95％CI，37-76）。截至2018年5月30日，仍有75％的反应者仍然有反应，而64％的接受治疗的患者持续反应。DOR，PFS和OS的12个月率为83％（95％CI，60-93），71％（95％CI，50-84）和86％（95％CI，66-94），分别; 没有达到中位数。最常见的≥3级AE是贫血（54％），血小板计数下降（39％），和中性粒细胞减少症（36％）。Lee等人评估的3/4级细胞因子释放综合征（CRS）。（血液。2014年）和3/4级神经系统事件（NE）分别发生在18％和46％的患者中，没有5级事件。CRS和NE通常是可逆的。组织性肺炎发生1次5级AE。通过曲线下的峰和面积测得的CAR T细胞中值分别为99个细胞/ µL（范围0.4-2589）和1542个细胞/ µL（范围5.5-27239）。

结论

经过≥1年的随访，KTE-X19表现出显着而持久的临床益处，对于R / R MCL且无治疗选择的患者，其安全性可控。