决定异体 CAR T 细胞排斥与扩增的细胞和分子机制
Cellular and molecular mechanisms determining allogeneic CAR T cell rejection and expansion.
我们评估了11例接受单一批次cemacabtagene ansegedleucel(cema-cel)治疗的大B细胞淋巴瘤患者,cemacabtagene ansegedleucel是一种异体抗CD19 CAR T产品。
英文原题:Treatment and survival outcomes for patients with follicular lymphoma and POD24: a systematic review and meta-analysis.
24 个月内疾病进展(POD24)的滤泡性淋巴瘤预后不良,是临床上的挑战。
进展性疾病在24个月内发生(POD24)的滤泡性淋巴瘤与预后不良相关,且带来临床挑战。因此,我们对POD24患者开展系统综述和汇总分析。共纳入21项试验、1242名参与者,评估总缓解率(ORR)、完全缓解(CR)、缓解持续时间和无进展生存期。在部分试验中,我们比较相同治疗方案下POD24与非POD24人群的汇总应答率。4项试验评估CAR-T细胞疗法治疗POD24患者。汇总分析显示,ORR为91.2%(95%置信区间[CI] 83.7–98.7),存在显著异质性(P=0.0414;I²=68.61%);CR率为75.7%(95% CI 55.1–96.4),异质性显著(P<0.0001;I²=93.99%)。对POD24患者使用不同双特异性抗体的特定应答率进行汇总分析,ORR为81.6%(95% CI 75.9–87.3),无异质性(P=0.6958;I²=0%);CR率为65.7%(95% CI 57.1–74.3),存在中度异质性(P=0.2148;I²=34.99%)。抗CD19抗体药物偶联物(ADC)/单克隆抗体(mAb)方面,loncastuximab联合rituximab以及tafasitamab联合R2(lenalidomide+rituximab)的ORR和CR率分别为100%和79.3%、87.5%和43.2%。研究还汇总分析了磷脂酰肌醇3-激酶抑制剂及含抗CD20 mAb的方案。结果显示抗CD19 CAR-T疗法取得最高CR率。此外,双特异性抗体、抗CD19 ADC/mAb,以及lenalidomide联合obinutuzumab或rituximab也显示出良好疗效。值得注意的是,lenalidomide联合obinutuzumab疗效优于R2方案。
Follicular lymphoma with progression of disease within 24 months (POD24) is associated with poor prognosis and represents clinical challenges. Therefore, we performed a systematic review and pooled analysis of patients with POD24. Twenty-one trials involving 1242 participants were included, assessing the overall response rate (ORR), complete response (CR), duration of response, and progression-free survival. In some trials, we compared pooled response rates between POD24 and non-POD24 populations with the same treatment regimen. Four trials evaluated chimeric antigen receptor (CAR) T-cell therapy in patients with POD24. Pooled analysis showed an ORR of 91.2% (95% confidence interval [CI], 83.7-98.7) with significant heterogeneity (P = .0414; I2 = 68.61%) and a CR of 75.7% (95% CI, 55.1-96.4) with significant heterogeneity (P< .0001; I2 = 93.99%). The specific response rates for different bispecific antibodies in POD24 were pooled analysis, the ORR was 81.6% (95% CI, 75.9-87.3) with no heterogeneity (P = .6958; I2 = 0%), and the CR was 65.7% (95% CI, 57.1-74.3) with moderate heterogeneity (P = .2148; I2 = 34.99%). For anti-CD19 antibody-drug conjugates (ADCs)/monoclonal antibodies (mAbs), the ORR and CR rate for loncastuximab plus rituximab and tafasitamab plus R2 (lenalidomide + rituximab) were 100% and 79.3%, and 87.5% and 43.2%, respectively. Phosphatidylinositol 3-kinase inhibitors and anti-CD20 mAb-containing regimens were also analyzed in pooled analyses. Our results demonstrated that anti-CD19 CAR T-cell therapy achieved the highest CR rate. Additionally, bispecific antibodies, anti-CD19 ADCs/mAbs, and the combination of lenalidomide with obinutuzumab or rituximab also exhibited excellent efficacy. Notably, lenalidomide plus obinutuzumab showed superior efficacy compared with R2.
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