CAR-T(CAR-T)细胞疗法在非肿瘤性疾病中的应用
Chimeric antigen receptor T (CAR-T) cell therapy in non-oncological diseases.
CAR-T(CAR-T)细胞在血液系统恶性肿瘤中的应用推动了这种免疫治疗形式的显著进展。
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:CAR19/22 T cell cocktail therapy for B-ALL relapsed after allogeneic hematopoietic stem cell transplantation.
CAR19/22 T cell cocktail therapy for B-ALL relapsed after allogeneic hematopoietic stem cell transplantation.
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B细胞急性淋巴细胞白血病(B-ALL)患者在接受造血干细胞移植(HSCT)后复发预后较差,目前尚无标准治疗方法。嵌合抗原受体(CAR)-T细胞在B细胞恶性肿瘤患者中,尤其是B-ALL,可诱导高初始缓解率和长期缓解。
同时,序贯输注CAR19/22 T细胞已被证明可有效预防肿瘤免疫逃逸。在本研究中,我们回顾性分析了本中心2016年7月至2020年7月期间23例接受异基因(allo)-HSCT后复发并接受序贯输注CAR19/22 T细胞的B-ALL患者,其中9例为供者来源,14例为受者来源,以评估两种单特异性CAR-T 细胞联合方案在移植后复发B-ALL患者中的安全性和疗效。除1例患者拒绝评估外,其余22例患者在CAR-T 输注后30天内均达到微小残留病(MRD)阴性完全缓解。大多数毒性轻微且可逆。估计12个月无进展生存期(PFS)率为59.2%(95%置信区间[CI],35.9%至76.5%),估计12个月总生存期(OS)率为67.4%(95% CI,43.2%至83.1%)。仅2例患者出现CD19阴性复发。
此外,移植后早期复发、移植物抗宿主病(GVHD)和CAR-T 输注后严重感染是不良预后因素。我们的结果表明,序贯输注CAR19/22 T细胞对HSCT后复发的ALL患者安全有效。该试验已在www.chictr.org.cn注册,注册号为#ChiCTR-OPN-16008526。
B cell acute lymphocytic leukemia (B-ALL) patients who have relapsed after hematopoietic stem cell transplantation (HSCT) have a poor prognosis, and there is currently no standard approach available. Chimeric antigen receptor (CAR)-T cells induce high rates of initial response and long-term remission among patients with B-cell malignancies, especially B-ALL. Meanwhile, sequential infusion of CAR19/22 T cells has been proven to be effective at preventing tumor immune escape. In the present study, we retrospectively analyzed 23 B-ALL patients who relapsed after allogeneic (allo)-HSCT and underwent sequential infusion of CAR19/22 T cells, including nine donor-derived and 14 recipient-derived, in our center from July 2016 to July 2020, to evaluate the safety and efficacy of the cocktail of two single-specific CAR-T cells in B-ALL patients relapsed after transplantation.
Except for one patient refusing evaluation, the remaining 22 patients achieved minimal residual disease (MRD)-negative complete remission within 30 days after CAR-T infusion. Most toxicities were slight and reversible. The estimated 12-month progression-free survival (PFS) rate was 59. 2% (95% confidence interval [CI], 35. 9% to 76. 5%), and the estimated 12-month overall survival (OS) rate was 67. 4% (95% CI, 43. 2% to 83. 1%). Only two patients had CD19-negative recurrence.
In addition, early recurrence after transplantation, graft-versus-host disease (GVHD) and severe infection after CAR-T infusion were poor prognostic factors.
Our results indicate that sequential infusion of CAR19/22 T cells is safe and effective for relapsed ALL patients after HSCT. This trial was registered at www. chictr. org. cn as #ChiCTR-OPN-16008526.
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