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:A multicenter retrospective study of polatuzumab vedotin in patients with large B-cell lymphoma after CAR T-cell therapy.
A multicenter retrospective study of polatuzumab vedotin in patients with large B-cell lymphoma after CAR T-cell therapy.
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Polatuzumab vedotin(PV)是一种靶向CD79b的抗体药物偶联物,已获批用于复发/难治性大B细胞淋巴瘤(LBCL)患者。注册研究未纳入嵌合抗原受体(CAR)T细胞治疗后复发的患者,CAR-T 治疗后使用PV的报告也有限。本项多中心回顾性分析纳入2019年7月至2021年5月间CAR-T 治疗后复发或进展、随后接受PV单药或联合利妥昔单抗和苯达莫司汀治疗的LBCL患者。根据2014年Lugano标准评估治疗应答和疾病进展。共纳入57例患者:18例(32%)对CAR-T 治疗原发难治;34例(60%)在CAR-T 治疗后立即接受PV方案。54例(95%)PV联合利妥昔单抗,35例(61%)联合苯达莫司汀。25例(44%)达到应答,其中8例(14%)完全缓解。未观察到基线特征与应答之间存在显著关联。中位随访47周(95%置信区间[CI],40–54)后,46例(81%)患者出现疾病进展或死亡,中位无进展生存期为10周(95% CI,5–15)。多变量分析显示,骨髓受累(风险比5.2;95% CI,1.8–15;P=0.003)和乳酸脱氢酶水平升高(风险比5.0;95% CI,1.4–16;P=0.01)与较短无进展生存期相关。需要开展研究,更好地描述这些患者的内在耐药机制并确定最佳巩固策略。
Polatuzumab vedotin (PV) is an antibody-drug conjugate targeting CD79b that is approved for patients with relapsed/refractory large B-cell lymphoma (LBCL). Patients who relapse after chimeric antigen receptor (CAR) T-cell therapy were not included in the registration study, and reports of PV use after CAR T cells are limited. This multicenter retrospective analysis included patients with LBCL who relapsed or progressed after CAR T-cell therapy and subsequently received PV with or without rituximab and bendamustine between July 2019 and May 2021. Response to treatment and progression were assessed based on the 2014 Lugano criteria. Fifty-seven patients were included in the study: 18 (32%) patients were primary refractory to CAR T-cell therapy, and 34 (60%) patients received PV-based therapy immediately after CAR T-cell therapy.
PV was combined with rituximab in 54 (95%) patients and administered with bendamustine in 35 (61%) patients. A response was achieved in 25 (44%) patients, including complete remission in 8 (14%). No significant association between baseline characteristics and response was observed. After a median follow-up of 47 weeks (95% confidence interval [CI], 40-54), 46 (81%) patients had disease progression or died, and the median progression-free survival was 10 weeks (95% CI, 5-15).
On a multivariate analysis, bone marrow involvement (hazard ratio, 5. 2; 95% CI, 1. 8-15; P = . 003) and elevated lactate dehydrogenase levels (hazard ratio, 5. 0; 95% CI, 1. 4-16; P = . 01) were associated with shorter progression-free survival. Studies aimed at better characterizing the intrinsic mechanism of resistance and identifying optimal consolidation strategies for these patients are warranted.
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