Efficacy and safety of CD19-specific CAR-T cell-based therapy in secondary central nervous system lymphoma.
Efficacy and safety of CD19-specific CAR-T cell-based therapy in secondary central nervous system lymphoma.
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CD19特异性CAR-T细胞治疗继发性中枢神经系统淋巴瘤的疗效和安全性
DOI：
10.3389/fimmu.2022.965224
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发表时间：
2022
影响因子：
7.3
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中科院分区：
文献类型：
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在通过嵌合抗原受体T（CAR-T）细胞治疗的复发性/难治性（R/R）B细胞淋巴瘤中已经实现了令人鼓舞的应答。CAR-T细胞在中枢神经系统淋巴瘤（CNSL）中的有效性和安全性仍然难以捉摸。在这里，我们回顾性分析了15例接受基于CD 19特异性CAR-T细胞治疗的R/R继发性CNSL患者。在环磷酰胺和氟达拉滨的预处理方案后，患者输注了CD 19、CD 19/CD 20或CD 19/CD 22 CAR-T细胞。总有效率为73.3%（11/15），其中完全缓解（CR）9例（60%），部分缓解（PR）2例（13.3%）。中位随访12个月，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例全身肿瘤浸润的患者中，7例（58.3%）CNS达到CR，5例（41.7%）CNS和全身均达到CR。CNS和全身性疾病的中位DOR分别为8个月和4个月。在观察终点，7例患者达到CNS疾病CR，1例患者仍然存活，CNS疾病和全身性疾病持续CR。其余6例死于全身性进展。15例患者中，11例（73.3%）发生1-2级CRS，无患者发生3-4级CRS。3例（20%）患者发生免疫效应细胞相关神经毒性综合征（ICANS），其中1例（6.6%）为4级ICANS。所有CRS或ICANS都是可管理的。基于CD 19特异性CAR-T细胞的治疗似乎是继发性CNSL的一种有前途的治疗方法，基于其抗肿瘤作用和可接受的副作用特征，同时需要更多的策略来维持应答。
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.