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嵌合抗原受体修饰 T 细胞免疫治疗复发/难治性成人伯基特淋巴瘤

英文原题:Chimeric Antigen Receptor-Modified T Cell Immunotherapy for Relapsed and Refractory Adult Burkitt Lymphoma.

PubMed 2022/05/20(内容时间) Front Immunol Q1 · IF 7(JCR 2025)

研究概要

共入组 28 例 r/r 伯基特淋巴瘤成人患者[试验 A(n = 15)和试验 B(n = 13)]。

中文摘要

初始治疗难治或接受强化化疗和自体干细胞移植(ASCT)后复发的 Burkitt 淋巴瘤患者通常预后较差。嵌合抗原受体(CAR)修饰 T 细胞免疫疗法治疗复发/难治性(r/r)恶性肿瘤已取得显著进展,但成人 r/r Burkitt 淋巴瘤患者的明确数据有限。我们开展了两项单臂临床试验,评估 CD19/CD22 CAR T 细胞免疫疗法单独使用(试验 A)及联合 ASCT(试验 B)治疗成人 r/r Burkitt 淋巴瘤的临床疗效和毒性。共纳入 28 例成人患者[试验 A(n=15),试验 B(n=13)]。CD22 和 CD19 CAR T 细胞输注剂量中位数分别为每千克 4.1×10⁶ 和 4.0×10⁶ 个。输注后,19 例(67.9%)患者获得总体缓解,16 例(57.1%)达到完全缓解。2–4 级细胞因子释放综合征和免疫效应细胞相关神经毒性综合征的累积发生率分别为 39.3%(11/28)和 10.7%(3/28)。中位随访 12.5 个月后,16 例患者存活(试验 A 5 例、试验 B 11 例)。估计 1 年无进展生存率和总生存率均为 55.6%。初步结果提示,单独输注 CD19/CD22 CAR T 细胞以及联合 ASCT 的挽救治疗,对部分成人 r/r Burkitt 淋巴瘤患者有效。

展开英文摘要原文

Patients with Burkitt lymphoma who are refractory to initial therapy or who relapse after undergoing intensive chemotherapy and autologous stem cell transplantation (ASCT) usually have a poor prognosis. While there has been considerable progress in the use of chimeric antigen receptor-modified (CAR) T cell immunotherapy for the treatment of relapsed and refractory (r/r) malignancies, explicit data on adult patients with r/r Burkitt lymphoma are limited. We conducted two single-arm clinical trials to evaluate the clinical efficacy and toxicity of CD19/CD22 CAR T cell immunotherapy both alone (trial A) and in combination with ASCT (trial B) in adult patients with r/r Burkitt lymphoma. In total, 28 adult patients with r/r Burkitt lymphoma were enrolled [trial A (n = 15) and trial B (n = 13)]. The median doses of CD22 and CD19 CAR T cell infusions were 4.1 10 6 /kg and 4.0 10 6 /kg, respectively. Subsequently, after CAR T cell infusion, overall and complete responses were observed in 19 (67.9%) and 16 (57.1%) patients, respectively. The cumulative incidence rates of grade 2-4 cytokine release syndrome and immune effector cell-associated neurotoxicity syndrome were 39.3% (11/28) and 10.7% (3/28), respectively. After a median follow-up duration of 12.5 months, 16 patients (5 in trial A and 11 in trial B) survived. Both the estimated 1-year progression-free and overall survival rates were 55.6%. Our preliminary results indicated that salvage therapy with CD19/CD22 CAR T cell infusion alone and that in combination with ASCT are effective in treating some adult patients with r/r Burkitt lymphoma.

论文信息

作者
Wu J、Cao Y、Zhang Q、Liu W、Zhou X、Ming X、Meng F、Zhang Y
单位
Department of Hematology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.China
文献类型
非美国政府资助研究
期刊
Frontiers in immunology2022
原文标识
PubMed 35669773 · DOI 10.3389/fimmu.2022.879983