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.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Associations of granulocyte colony-stimulating factor with toxicities and efficacy of chimeric antigen receptor T-cell therapy in relapsed or refractory B-cell acute lymphoblastic leukemia.
Associations of granulocyte colony-stimulating factor with toxicities and efficacy of chimeric antigen receptor T-cell therapy in relapsed or refractory B-cell acute lymphoblastic leukemia.
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复发/难治性(R/R)B细胞急性淋巴细胞白血病(B-ALL)患者接受嵌合抗原受体(CAR)T细胞治疗后,粒细胞集落刺激因子(G-CSF)与细胞因子释放综合征(CRS)、神经毒性事件(NE)和疗效之间的关联研究较少。
我们回顾性分析了67例接受抗CD19 CAR-T 治疗的R/R B-ALL患者,其中41例(61.2%)接受G-CSF(G-CSF组),26例(38.8%)未接受(非G-CSF组)。两组3–4级中性粒细胞减少持续时间相似。G-CSF组CRS和NE发生率更高,但严重程度无差异。
进一步分层分析显示,对于骨髓(BM)肿瘤负荷低的患者,CRS发生率和严重程度均与G-CSF给药无关,且无低BM肿瘤负荷患者发生NE。
然而,对于BM肿瘤负荷高的患者,给予G-CSF后CRS发生率显著增加。接受G-CSF患者的CRS持续时间更长。CAR-T 输注后1个月和3个月的缓解率以及两组总生存期(OS)均无显著差异。
总之,对于BM肿瘤负荷低的患者,G-CSF给药与CRS发生率或严重程度无关;而对于BM肿瘤负荷高的患者,G-CSF给药后CRS发生率较高,且CRS持续时间在G-CSF组延长。G-CSF给药与CAR-T 疗效无关。
Few studies have reported the associations of granulocyte colony-stimulating factor (G-CSF) with cytokine release syndrome (CRS), neurotoxic events (NEs) and efficacy after chimeric antigen receptor (CAR) T-cell therapy for relapsed or refractory (R/R) B-cell acute lymphoblastic leukemia (B-ALL).
We present a retrospective study of 67 patients with R/R B-ALL who received anti-CD19 CAR T-cell therapy, 41 (61. 2%) patients received G-CSF (G-CSF group), while 26 (38. 8%) did not (non-G-CSF group). Patients had similar duration of grade 3-4 neutropenia between the two groups. The incidences of CRS and NEs were higher in G-CSF group, while no differences in severity were found.
Further stratified analysis showed that the incidence and severity of CRS were not associated with G-CSF administration in patients with low bone marrow (BM) tumor burden. None of the patients with low BM tumor burden developed NEs.
However, there was a significant increase in the incidence of CRS after G-CSF administration in patients with high BM tumor burden. The duration of CRS in patients who used G-CSF was longer. There were no significant differences in response rates at 1 and 3 months after CAR T-cell infusion, as well as overall survival (OS) between the two groups.
In conclusion, our results showed that G-CSF administration was not associated with the incidence or severity of CRS in patients with low BM tumor burden, but the incidence of CRS was higher after G-CSF administration in patients with high BM tumor burden. The duration of CRS was prolonged in G-CSF group. G-CSF administration was not associated with the efficacy of CAR T-cell therapy.
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