High rate of durable complete remission in follicular lymphoma after CD19 CAR-T cell immunotherapy
High rate of durable complete remission in follicular lymphoma after CD19 CAR-T cell immunotherapy
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DOI：
10.1182/blood.2019000905
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发表时间：
2019-08-15
期刊：
影响因子：
20.3
通讯作者：
Turtle, Cameron J.
中科院分区：
文献类型：
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作者：
Hirayama, Alexandre V.;Gauthier, Jordan;Turtle, Cameron J.
滤泡性淋巴瘤（FL）患者在初始化学免疫治疗后早期复发、难治性疾病或组织学转化（tFL）的无进展生存期和总生存期有限。我们报告了21例复发性/难治性（R/R）FL（n = 8）和tFL（n = 13）患者的疗效和长期随访，这些患者在1/2期临床试验中接受环磷酰胺和氟达拉滨淋巴细胞清除治疗，然后输注2 x 10（6）CD 19定向嵌合抗原受体修饰的T（CAR-T）细胞/kg。根据Lugano标准，FL和tFL患者的完全缓解（CR）率分别为88%和46%。所有达到CR的FL患者在中位随访24个月时保持缓解。中位随访38个月时，tFL患者的中位缓解持续时间为10.2个月。FL和tFL患者中分别有50%和39%发生细胞因子释放综合征，50%和23%发生神经毒性，无严重不良事件（≥ 3级）。在FL和tFL患者之间未观察到CAR-T细胞体内扩增/持久性的显著差异。CD 19 CAR-T细胞免疫疗法在有或无转化的临床侵袭性R/R FL成人中非常有效，在高比例的FL患者中具有持久缓解。
Patients with follicular lymphoma (FL) with early relapse after initial chemoimmunotherapy, refractory disease, or histologic transformation (tFL) have limited progression-free and overall survival. We report efficacy and long-term follow-up of 21 patients with relapsed/refractory (R/R) FL (n = 8) and tFL (n = 13) treated on a phase 1/2 clinical trial with cyclophosphamide and fludarabine lymphodepletion followed by infusion of 2 x 10(6) CD19-directed chimeric antigen receptor-modified T (CAR-T) cells per kilogram. The complete remission (CR) rates by the Lugano criteria were 88% and 46% for patients with FL and tFL, respectively. All patients with FL who achieved CR remained in remission at a median follow-up of 24 months. The median duration of response for patients with tFL was 10.2 months at a median follow-up of 38 months. Cytokine release syndrome occurred in 50% and 39%, and neurotoxicity in 50% and 23% of patients with FL and tFL, respectively, with no severe adverse events (grade >= 3). No significant differences in CAR-T cell in vivo expansion/persistence were observed between FL and tFL patients. CD19 CAR-T cell immunotherapy is highly effective in adults with clinically aggressive R/R FL with or without transformation, with durable remission in a high proportion of FL patients.