Chimeric Antigen Receptor-Modified T Cell Immunotherapy for Relapsed and Refractory Adult Burkitt Lymphoma.
Chimeric Antigen Receptor-Modified T Cell Immunotherapy for Relapsed and Refractory Adult Burkitt Lymphoma.
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嵌合抗原受体修饰 T 细胞免疫疗法治疗复发性和难治性成人伯基特淋巴瘤
DOI：
10.3389/fimmu.2022.879983
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发表时间：
2022
影响因子：
7.3
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中科院分区：
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伯基特淋巴瘤的患者谁是难治性的初始治疗或复发后，接受强化化疗和自体干细胞移植（ASCT）通常有预后不良。虽然在使用嵌合抗原受体修饰的（CAR）T细胞免疫疗法治疗复发性和难治性（r/r）恶性肿瘤方面取得了相当大的进展，但关于成人r/r伯基特淋巴瘤患者的明确数据有限。我们进行了两项单臂临床试验，以评估CD 19/CD 22 CAR T细胞免疫疗法单独（试验A）和与ASCT联合（试验B）治疗成人r/r伯基特淋巴瘤患者的临床疗效和毒性。总共入组了28例成人r/r伯基特淋巴瘤患者[试验A（n = 15）和试验B（n = 13）]。CD 22和CD 19 CAR T细胞输注的中位剂量分别为4.1 × 106/kg和4.0 × 106/kg。随后，在CAR T细胞输注后，分别在19例（67.9%）和16例（57.1%）患者中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）。中位随访时间为12.5个月后，16例患者（试验A中5例，试验B中11例）存活。1年无进展生存率和总生存率均为55.6%。我们的初步结果表明，单独输注CD 19/CD 22 CAR T细胞以及与ASCT联合输注的挽救治疗可有效治疗一些成人r/r Burkitt淋巴瘤患者。
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 × 106/kg and 4.0 × 106/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.