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:An alternative fully human anti-BCMA CAR-T shows response for relapsed or refractory multiple myeloma with anti-BCMA CAR-T exposures previously.
1-2 级细胞因子释放综合征(CRS)发生于 3 例患者(42.9%),3 级发生于 2 例患者(28.6%)。
CAR-T(CAR-T)细胞疗法在复发/难治性多发性骨髓瘤(R/R MM)治疗中取得显著进展。遗憾的是,即使接受抗BCMA CAR-T治疗,患者最终仍可能出现疾病进展或复发。目前,对于抗BCMA CAR-T治疗后进展的患者,可选治疗方案的数据有限。本研究评估了全人源抗BCMA CAR-T(HRC0202)在7例既往接受过抗BCMA CAR-T治疗的R/R MM患者中的安全性和疗效。3例患者接受6.0×10⁶ CAR+ T细胞/kg,1例接受10.0×10⁶ CAR+ T细胞/kg,3例接受15.0×10⁶ CAR+ T细胞/kg。3例患者(42.9%)发生1–2级细胞因子释放综合征(CRS),2例(28.6%)发生3级CRS。所有患者均未观察到免疫效应细胞相关神经毒性综合征(ICANS)。最佳总体缓解率(ORR)为71.4%(5/7),其中3例达到严格完全缓解/完全缓解(sCR/CR)。无进展生存期(PFS)中位数为269天,所有患者的总生存期(OS)中位数尚未达到。HRC0202的中位峰值浓度(Cmax)为30,117.70拷贝/μg DNA(范围:6,084.35–147,415.10)。本研究提示,对于既往接受抗BCMA CAR-T输注后复发或难治的R/R MM患者,全人源抗BCMA CAR-T(HRC0202)是一种有前景的治疗选择。
Chimeric antigen receptor T (CAR-T) cells therapy has made remarkable progress in relapsed/refractory multiple myeloma (R/R MM) treatment. Unfortunately, patients still eventually experience disease progression or relapse even after receiving anti-BCMA CAR-T therapy. At present, there are limited data on available treatment options for patients who have progressed on anti-BCMA CAR-T therapy. In this study, we evaluated the safety and efficacy of fully human anti-BCMA CAR-T (HRC0202) in seven R/R MM patients who were previously exposed to anti-BCMA CAR-T therapy. Three patients received 6.0 10 6 CAR + T cells/kg, one patient received 10.0 10 6 CAR + T cells/kg and three patients received 15.0 10 6 CAR + T cells/kg. Cytokine release syndrome (CRS) of grades 1-2 occurred in three patients (42.9%) and grade 3 in two patients (28.6%). Immune effector cell-associated neurotoxic syndrome (ICANS) was not observed in any of the patients. The best overall response rate (ORR) was 71.4% (5/7), with a stringent complete response/complete response (sCR/CR) achieved in three patients. The median progression-free survival (PFS) was 269 days, and median overall survival (OS) for all patients was not reached. The median peak concentration (C max ) of HRC0202 was 30117.70 (range, 6084.35-147415.10) copies/ g DNA. This study indicated that fully human anti-BCMA CAR-T (HRC0202) is a promising treatment for R/R MM patients who relapsed or refractory from prior anti-BCMA CAR-T infusion.
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