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:Efficacy and safety of CD19-specific CAR-T cell-based therapy in secondary central nervous system lymphoma.
在此,我们回顾性分析了15例接受CD19特异性CAR-T细胞治疗的R/R继发性CNSL患者。
在复发/难治性(R/R)B细胞淋巴瘤中,CAR-T(CAR-T)细胞治疗已取得令人鼓舞的缓解。CAR-T细胞在中枢神经系统淋巴瘤(CNSL)中的疗效和安全性仍不明确。在此,我们回顾性分析了15例接受CD19特异性CAR-T细胞治疗的R/R继发性CNSL患者。患者在环磷酰胺和氟达拉滨预处理方案后输注CD19、CD19/CD20或CD19/CD22 CAR-T细胞。总缓解率为73.3%(11/15),其中9例(60%)达到完全缓解(CR),2例(13.3%)达到部分缓解(PR)。在中位随访12个月期间,中位无进展生存期(PFS)为4个月,中位总生存期(OS)为9个月。在12例伴有全身肿瘤浸润的患者中,7例(58.3%)在CNS中达到CR,5例(41.7%)在全身和CNS中均达到CR。CNS和全身疾病的中位DOR分别为8个月和4个月。在观察终点时,7例达到CNS疾病CR的患者中,1例仍存活,CNS疾病和全身疾病均持续CR。其余6例死于全身进展。在15例患者中,11例(73.3%)发生1-2级CRS,无患者发生3-4级CRS。免疫效应细胞相关神经毒性综合征(ICANS)发生于3例(20%)患者,包括1例(6.6%)4级ICANS。所有CRS或ICANS均可控制。基于其抗肿瘤效应和可接受的副作用特征,CD19特异性CAR-T细胞治疗似乎是继发性CNSL的一种有前景的治疗方法,同时需要更多策略来维持缓解。
Encouraging response has been achieved in relapsed/refractory (R/R) B-cell lymphoma treated by chimeric antigen receptor T (CAR-T) cells. The efficacy and safety of CAR-T cells in central nervous system lymphoma (CNSL) are still elusive. Here, we retrospectively analyzed 15 patients with R/R secondary CNSL receiving CD19-specific CAR-T cell-based therapy. The patients were infused with CD19, CD19/CD20 or CD19/CD22 CAR-T cells following a conditioning regimen of cyclophosphamide and fludarabine. The overall response rate was 73.3% (11/15), including 9 (60%) with complete remission (CR) and 2 (13.3%) with partial remission (PR). During a median follow-up of 12 months, the median progression-free survival (PFS) was 4 months, and the median overall survival (OS) was 9 months. Of 12 patients with systemic tumor infiltration, 7 (58.3%) achieved CR in CNS, and 5 (41.7%) achieved CR both systemically and in CNS. Median DOR for CNS and systemic disease were 8 and 4 months, respectively. At the end point of observation, of the 7 patients achieved CNS disease CR, one was still alive with sustained CR of CNS disease and systemic disease. The other 6 died of systemic progression. Of the 15 patients, 11 (73.3%) experienced grades 1-2 CRS, and no patient had grades 3-4 CRS. Immune effector cell-associated neurotoxicity syndrome (ICANS) occurred in 3 (20%) patients, including 1 (6.6%) with grade 4 ICANS. All the CRS or ICANS were manageable. The CD19-specific CAR-T cell-based therapy appeared to be a promising therapeutic approach in secondary CNSL, based on its antitumor effects and an acceptable side effect profile, meanwhile more strategies are needed to maintain the response.
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