Background

Patients with relapsed or refractory mantle-cell lymphoma who have disease progression during or after the receipt of Bruton’s tyrosine kinase (BTK) inhibitor therapy have a poor prognosis. KTE-X19, an anti-CD19 chimeric antigen receptor (CAR) T-cell therapy, may have benefit in patients with relapsed or refractory mantle-cell lymphoma.

Methods

In a multicenter, phase 2 trial, we evaluated KTE-X19 in patients with relapsed or refractory mantle-cell lymphoma. Patients had disease that had relapsed or was refractory after the receipt of up to five previous therapies; all patients had to have received BTK inhibitor therapy previously. Patients underwent leukapheresis and optional bridging therapy, followed by conditioning chemotherapy and a single infusion of KTE-X19 at a dose of 2×10⁶ CAR T cells per kilogram of body weight. The primary end point was the percentage of patients with an objective response (complete or partial response) as assessed by an independent radiologic review committee according to the Lugano classification. Per the protocol, the primary efficacy analysis was to be conducted after 60 patients had been treated and followed for 7 months.

Results

A total of 74 patients were enrolled. KTE-X19 was manufactured for 71 patients and administered to 68. The primary efficacy analysis showed that 93% (95% confidence interval [CI], 84 to 98) of the 60 patients in the primary efficacy analysis had an objective response; 67% (95% CI, 53 to 78) had a complete response. In an intention-to-treat analysis involving all 74 patients, 85% had an objective response; 59% had a complete response. At a median follow-up of 12.3 months (range, 7.0 to 32.3), 57% of the 60 patients in the primary efficacy analysis were in remission. At 12 months, the estimated progression-free survival and overall survival were 61% and 83%, respectively. Common adverse events of grade 3 or higher were cytopenias (in 94% of the patients) and infections (in 32%). Grade 3 or higher cytokine release syndrome and neurologic events occurred in 15% and 31% of patients, respectively; none were fatal. Two grade 5 infectious adverse events occurred.

Conclusions

KTE-X19 induced durable remissions in a majority of patients with relapsed or refractory mantle-cell lymphoma. The therapy led to serious and life-threatening toxic effects that were consistent with those reported with other CAR T-cell therapies. (Funded by Kite, a Gilead company; ZUMA-2 ClinicalTrials.gov number, NCT02601313.)

中文翻译：

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KTE-X19 CAR T细胞疗法在复发性或难治性套细胞淋巴瘤中的应用。

背景

在接受布鲁顿酪氨酸激酶（BTK）抑制剂治疗期间或之后疾病进展的复发性或难治性套细胞淋巴瘤患者的预后较差。KTE-X19是一种抗CD19嵌合抗原受体（CAR）T细胞疗法，可能对复发或难治的套细胞淋巴瘤患者有益。

方法

在一项多中心2期试验中，我们评估了复发或难治性套细胞淋巴瘤患者的KTE-X19。在接受多达五种先前的治疗后，患者的疾病已复发或难治；所有患者以前都必须接受BTK抑制剂治疗。患者接受白细胞分离术和可选的桥接治疗，然后进行条件化疗和单次输注KTE-X19，剂量为2×10 ⁶每千克体重CAR T细胞。主要终点是由独立放射学审查委员会根据Lugano分类评估的具有客观缓解（完全缓解或部分缓解）的患者百分比。根据方案，将在治疗60例患者后进行7个月的主要疗效分析。

结果

共有74名患者入选。生产的KTE-X19可治疗71例患者，可治疗68例。主要疗效分析显示，在60例主要疗效分析中，有93％（95％置信区间[CI]为84至98）有客观反应。67％（95％CI，53至78）完全反应。在涉及所有74例患者的意向性治疗分析中，有85％的患者有客观反应。59％的人有完整的回应。在中位随访时间为12.3个月（范围7.0至32.3）中，主要疗效分析中60例患者中有57％处于缓解状态。在12个月时，估计的无进展生存期和总生存期分别为61％和83％。3级或更高级别的常见不良事件是血细胞减少（94％的患者）和感染（32％）。15％和31％的患者发生3级或更高级别的细胞因子释放综合征和神经系统事件；没有一个是致命的。发生了两个5级感染不良事件。

结论

KTE-X19在大多数复发或难治的套细胞淋巴瘤患者中引起持久缓解。该疗法导致严重且危及生命的毒性作用，与其他CAR T细胞疗法报道的结果一致。（由Gilead公司Kite资助； ZUMA-2 ClinicalTrials.gov编号，NCT02601313。）