Department of Hematology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Wuhan Bio-Raid Biotechnology Co. Ltd., Wuhan, China.
Front Immunol. 2022 May 20;13:879983. doi: 10.3389/fimmu.2022.879983. eCollection 2022.
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/kg and 4.0 × 10/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.
对于初始治疗耐药或在接受强化化疗和自体干细胞移植 (ASCT) 后复发的伯基特淋巴瘤患者,通常预后较差。虽然嵌合抗原受体修饰 (CAR) T 细胞免疫疗法在治疗复发和难治性 (r/r) 恶性肿瘤方面取得了相当大的进展,但关于 r/r 伯基特淋巴瘤成年患者的数据有限。我们进行了两项单臂临床试验,以评估 CD19/CD22 CAR T 细胞免疫疗法单独(试验 A)和联合 ASCT(试验 B)在 r/r 伯基特淋巴瘤成年患者中的临床疗效和毒性。共有 28 例 r/r 伯基特淋巴瘤成年患者入组 [试验 A(n=15)和试验 B(n=13)]。CD22 和 CD19 CAR T 细胞输注的中位剂量分别为 4.1×10/kg 和 4.0×10/kg。随后,在 CAR T 细胞输注后,19 例(67.9%)和 16 例(57.1%)患者分别观察到总体和完全缓解。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(试验 A 中 5 例,试验 B 中 11 例)存活。估计 1 年无进展生存率和总生存率分别为 55.6%。我们的初步结果表明,单独使用 CD19/CD22 CAR T 细胞输注和联合 ASCT 的挽救疗法在治疗一些 r/r 伯基特淋巴瘤成年患者中是有效的。
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