CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
儿童、青少年和年轻成人中 tisagenlecleucel 治疗 B 细胞急性淋巴细胞白血病失败的特征和结局决定因素
英文原题：Characteristics and outcome determinants in children, adolescents and young adults who failed tisagenlecleucel for B-cell acute lymphoblastic leukemia.
查看英文原题
Characteristics and outcome determinants in children, adolescents and young adults who failed tisagenlecleucel for B-cell acute lymphoblastic leukemia.
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中文摘要
自体抗CD19嵌合抗原受体（CAR）T细胞疗法替沙仑赛（tisa-cel）显著改善了复发/难治性B细胞前体急性淋巴细胞白血病（R/R BCP-ALL）儿童、青少年和青年患者的结局。
然而，仍有30%–50%的患者发生早期治疗失败或复发。我们回顾性分析了52例早期治疗失败（n=13）或复发（n=39）病例，评估tisa-cel治疗后的结局及预后因素。CD19抗原丢失是唯一与挽救治疗后完全缓解率较低相关的因素（OR=0.16，95% CI：0.03–0.90，p=0.04）。总生存期（OS）中位数为14.5个月，2年OS率为37.4%（95% CI：24.4–50.4）；早期失败组（38.5%）与复发组（37.0%）相近（p=0.78）。挽救治疗开始时仅存在可测量残留病的患者，其2年OS显著更高，为61.9%（95% CI：38.1–78.8），而显性疾病患者为20.7%（95% CI：8.4–36.7，p=0.008）。与OS较差相关的因素包括输注前肿瘤负荷较高（HR=3.57，p<0.01）及既往接受奥加伊妥珠单抗治疗（HR=3.81，p<0.01）。尽管挽救治疗和造血干细胞移植可使部分患者获益，但18例移植患者中有5例死于治疗相关毒性，凸显其相关风险显著。研究结果显示tisa-cel治疗失败后预后较差，亟需新的治疗策略。
展开英文摘要原文
Tisagenlecleucel (tisa-cel), an autologous anti-CD19 CAR T-cell therapy, has significantly improved outcomes in pediatric, adolescents and young adults with relapsed/refractory B-cell precursor acute lymphoblastic leukemia (R/R BCP-ALL).
However, 30-50% experience early failure or relapse. We retrospectively analyzed 52 cases of early failures (n = 13) or relapses (n = 39), evaluating post-tisa-cel outcomes and prognostic factors. CD19 antigen loss was the only factor associated with a lower complete remission rate after salvage therapy (OR = 0. 16, 95%CI [0. 03-0. 90], p = 0. 04). Median overall survival (OS) was 14. 5 months, with a 2-year OS of 37. 4% (95%CI [24. 4-50. 4]), similar between early failure (38. 5%) and relapse (37. 0%) groups (p = 0. 78).
Patients with measurable residual disease only at salvage initiation had significantly improved 2-year OS (61. 9%, (95%CI [38. 1-78. 8])) compared to those with overt disease (20. 7%, (95%CI [8. 4-36. 7], p = 0. 008)). Factors associated with inferior OS included high pre-infusion tumor burden (HR = 3.
57, p < 0. 01), and prior inotuzumab ozogamicin exposure (HR = 3. 81, p < 0. 01). Although salvage therapies and hematopoietic stem cell transplantation benefit some patients, 5 of 18 transplanted patients died from treatment-related toxicity, underscoring the significant associated risks.
These findings highlight the poor prognosis of tisa-cel failures and the urgent need for novel strategies.
论文信息
- 作者
- Lecornec N、Rabian F、Dourthe ME、Chevillon F、Yakouben K、Chaillou D、Caillat-Zucman S、Cuffel A
- 第一作者单位
- Department of Pediatric Hematology and Immunology, Hôpital Universitaire Robert Debré, AP-HP and Université Paris Cité, Paris, France.France
- 通讯作者单位
- Adolescents and Young Adults Unit, Hôpital Universitaire Saint Louis, AP-HP and Université Paris Cité, Paris, France. nicolas.boissel@aphp.fr.France
- 期刊
- Leukemia2026 May
- 原文标识
- PubMed 41735483 · DOI 10.1038/s41375-026-02867-9