Department of Medicine V, University of Heidelberg, Heidelberg, Germany; and.
Institute for Clinical Transfusion Medicine and Cell Therapy, Heidelberg, Germany.
Blood Adv. 2020 Dec 22;4(24):6157-6168. doi: 10.1182/bloodadvances.2020003036.
CD19-directed chimeric antigen receptor (CAR) T-cell treatment has evolved as standard of care (SOC) for multiply relapsed/refractory (R/R) large B-cell lymphoma (LBCL). However, its potential benefit over allogeneic hematopoietic cell transplantation (alloHCT) remains unclear. We compared outcomes with both types of cellular immunotherapy (CI) by intention to treat (ITT). Eligble were all patients with R/R LBCL and institutional tumor board decision recommending SOC CAR T-cell treatment between July 2018 and February 2020, or alloHCT between January 2004 and February 2020. Primary end point was overall survival (OS) from indication. Altogether, 41 and 60 patients for whom CAR T cells and alloHCT were intended, respectively, were included. In both cohorts, virtually all patients had active disease at indication. CI was recommended as part of second-line therapy for 21 alloHCT patients but no CAR T-cell patients. Median OS from indication was 475 days with CAR T cells vs 285 days with alloHCT (P = .88) and 222 days for 39 patients for whom alloHCT beyond second line was recommended (P = .08). Of CAR T-cell and alloHCT patients, 73% and 65%, respectively, proceeded to CI. After CI, 12-month estimates for nonrelapse mortality, relapse incidence, progression-free survival, and OS for CAR T cells vs alloHCT were 3% vs 21% (P = .04), 59% vs 44% (P = .12), 39% vs 33% (P = .97), and 68% vs 54% (P = .32), respectively. In conclusion, CAR T-cell outcomes were not inferior to alloHCT outcomes, whether measured by ITT or from CI administration, supporting strategies preferring CAR T cells over alloHCT as first CI for multiply R/R LBCL.
CD19 导向嵌合抗原受体 (CAR) T 细胞治疗已成为多发性复发/难治性 (R/R) 大 B 细胞淋巴瘤 (LBCL) 的标准治疗方法 (SOC)。然而,其相对于异基因造血细胞移植 (alloHCT) 的潜在益处尚不清楚。我们通过意向治疗 (ITT) 比较了这两种细胞免疫疗法 (CI) 的结果。合格的是所有 R/R LBCL 患者,以及机构肿瘤委员会决定建议在 2018 年 7 月至 2020 年 2 月期间进行 SOC CAR T 细胞治疗,或在 2004 年 1 月至 2020 年 2 月期间进行 alloHCT。主要终点是从适应症开始的总生存期 (OS)。总共纳入了 41 名和 60 名分别计划接受 CAR T 细胞和 alloHCT 的患者。在两个队列中,几乎所有患者在适应症时都有活动疾病。21 名 alloHCT 患者和 0 名 CAR T 细胞患者将 CI 作为二线治疗的一部分推荐。从适应症开始,CAR T 细胞的中位 OS 为 475 天,alloHCT 为 285 天,39 名患者推荐二线以上 alloHCT 的中位 OS 为 222 天(P =.88)。CAR T 细胞和 alloHCT 患者中,分别有 73%和 65%的患者接受了 CI。接受 CI 后,CAR T 细胞与 alloHCT 的 12 个月非复发死亡率、复发率、无进展生存期和 OS 估计值分别为 3%比 21%(P =.04)、59%比 44%(P =.12)、39%比 33%(P =.97)和 68%比 54%(P =.32)。总之,无论通过 ITT 还是从 CI 管理来衡量,CAR T 细胞的结果都不劣于 alloHCT 的结果,支持将 CAR T 细胞作为多发性 R/R LBCL 的首选首次 CI 的策略。