Division of Hematology and Hemostaseology and Comprehensive Cancer Center, Department of Medicine I, Medical University of Vienna, Vienna, Austria.
Department of Blood Group Serology and Transfusion Medicine, Medical University of Vienna, Vienna, Austria.
Blood Adv. 2023 Jun 13;7(11):2283-2286. doi: 10.1182/bloodadvances.2022007779.
Tisagenlecleucel demonstrated high response rates and a manageable safety profile in adults with relapsed/refractory diffuse large B-cell lymphoma (r/r DLBCL) in the JULIET trial. However, lack of response and chimeric antigen receptor (CAR) T-cell exhaustion were observed in patients with programmed cell death protein 1 (PD-1) overexpression. Hence, pembrolizumab, a PD-1 inhibitor, was hypothesized to improve efficacy and cellular expansion of CAR T-cells in vivo. Here, we report the final analysis of the PORTIA trial in adult patients with r/r DLBCL who had ≥2 prior lines of therapy and had an Eastern Cooperative Oncology Group performance status of ≤1. Patients received 1 tisagenlecleucel infusion on day 1. Pembrolizumab (200 mg) was given every 21 days, for up to 6 doses. Three cohorts initiated pembrolizumab on days 15 (n = 4), 8 (n = 4), or -1 (n = 4). Safety, efficacy, cellular kinetics, and biomarker analyses were included. Tisagenlecleucel plus pembrolizumab was feasible and showed a manageable safety profile, without dose-limiting toxicities. Emerging efficacy with tisagenlecleucel was observed when pembrolizumab was given the day before tisagenlecleucel; however, the limited patient sample and short follow-up do not allow for definitive conclusions. Adding pembrolizumab to tisagenlecleucel did not augment the cellular expansion of tisagenlecleucel but delayed peak expansion if given the day before tisagenlecleucel (NCT03630159).
在 JULIET 试验中，Tisagenlecleucel 在既往接受过治疗的复发性/难治性弥漫性大 B 细胞淋巴瘤（r/r DLBCL）成年患者中表现出高缓解率和可管理的安全性特征。然而，在程序性细胞死亡蛋白 1（PD-1）过表达的患者中观察到缺乏反应和嵌合抗原受体（CAR）T 细胞衰竭。因此，假设 PD-1 抑制剂 pembrolizumab 可以提高 CAR T 细胞在体内的疗效和细胞扩增。在这里，我们报告了 PORTIA 试验在既往接受过≥2 线治疗且东部合作肿瘤学组（ECOG）体能状态≤1 的 r/r DLBCL 成年患者中的最终分析结果。患者在第 1 天接受 1 次 tisagenlecleucel 输注。pembrolizumab（200mg）每 21 天给药 1 次，最多 6 个剂量。3 个队列分别在第 15 天（n=4）、第 8 天（n=4）或第-1 天（n=4）开始使用 pembrolizumab。包括安全性、疗效、细胞动力学和生物标志物分析。Tisagenlecleucel 联合 pembrolizumab是可行的，具有可管理的安全性特征，无剂量限制毒性。当 pembrolizumab 在 tisagenlecleucel 前一天给予时，观察到 tisagenlecleucel 的疗效出现；然而，由于患者样本量有限且随访时间短，无法得出明确结论。在 tisagenlecleucel 前一天给予 pembrolizumab 并没有增强 tisagenlecleucel 的细胞扩增，但会延迟其峰值扩增（NCT03630159）。
