From the University of Texas M.D. Anderson Cancer Center, Houston (M.W.), and Texas Oncology, Dallas (H.H.); Banner M.D. Anderson Cancer Center, Gilbert, AZ (J.M.); John Theurer Cancer Center, Hackensack, NJ (A.G.); Moffitt Cancer Center, Tampa (F.L.L.), and the University of Miami, Miami (A.B.) - both in Florida; Dana-Farber Cancer Institute, Boston (C.A.J.); Cleveland Clinic Foundation, Cleveland (B.T.H.), and the Ohio State University Comprehensive Cancer Center, Columbus (S.J.); David Geffen School of Medicine at UCLA, Los Angeles (J.M.T.), Stanford University School of Medicine, Stanford (D.B.M.), and Kite, a Gilead company, Santa Monica (W.P., L.Z., J.M.R., R.K.J., A.V.R.) - all in California; Sarah Cannon Research Institute-Tennessee Oncology, Nashville (I.W.F.); Colorado Blood Cancer Institute, Denver (P.A.M.); Swedish Cancer Institute, Seattle (J.M.P.); the Academic Medical Center, University of Amsterdam, Amsterdam, for the Lunenburg Lymphoma Phase I/II Consortium (M.-J.K.); Centre Hospitalier Universitaire (CHU) Bordeaux, Service d'Hematologie et Therapie Cellulaire, Bordeaux (N.M.), and CHU Rennes, INSERM French Blood Establishment, Rennes (R.H.) - both in France; Fox Chase Cancer Center, Philadelphia (H.F.); Universitätsklinikum Würzburg, Würzburg, Germany (M.S.T.); and the University of Rochester Medical Center, Rochester, NY (P.M.R.).
N Engl J Med. 2020 Apr 2;382(14):1331-1342. doi: 10.1056/NEJMoa1914347.
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.
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 2×10 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.
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.
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.).
接受布鲁顿酪氨酸激酶（BTK）抑制剂治疗后疾病进展的复发或难治性套细胞淋巴瘤患者预后不良。嵌合抗原受体（CAR）T 细胞疗法 KTE-X19 可能对复发或难治性套细胞淋巴瘤患者有益。
在一项多中心、2 期试验中，我们评估了 KTE-X19 在复发或难治性套细胞淋巴瘤患者中的疗效。患者疾病在接受多达 5 种先前治疗后复发或难治；所有患者之前均接受过 BTK 抑制剂治疗。患者接受白细胞分离术和可选的桥接治疗，然后接受化疗预处理，并输注 2×10 CAR T 细胞/每千克体重的 KTE-X19。主要终点是根据卢加诺分类，由独立放射学审查委员会评估的客观缓解率（完全或部分缓解）。根据方案，主要疗效分析在 60 例患者接受治疗并随访 7 个月后进行。
共纳入 74 例患者。71 例患者接受了 KTE-X19 的生产，并给 68 例患者输注了药物。主要疗效分析显示，60 例主要疗效分析患者中 93%（95%置信区间 [CI]，84%至 98%）有客观缓解；67%（95%CI，53%至 78%）有完全缓解。在包括 74 例患者的意向治疗分析中，85%的患者有客观缓解；59%的患者有完全缓解。在中位随访 12.3 个月（范围为 7.0 至 32.3）时，60 例主要疗效分析患者中有 57%处于缓解状态。12 个月时，无进展生存率和总生存率分别为 61%和 83%。3 级或更高级别的常见不良事件为血细胞减少症（94%的患者）和感染（32%的患者）。3 级或更高级别的细胞因子释放综合征和神经系统事件分别发生在 15%和 31%的患者中，均无致命事件。2 例 5 级感染性不良事件。
KTE-X19 诱导大多数复发或难治性套细胞淋巴瘤患者持久缓解。该疗法导致严重和危及生命的毒性作用，与其他 CAR T 细胞疗法报告的毒性作用一致。（由 Kite，一家吉利德公司资助；ZUMA-2 临床试验.gov 编号，NCT02601313。）
