Clinical Research Division, Fred Hutchinson Cancer Center, Seattle, WA.
Division of Hematology and Oncology, Department of Medicine, University of Washington, Seattle, WA.
Blood Adv. 2023 Nov 28;7(22):6990-7005. doi: 10.1182/bloodadvances.2023011399.
High response rates have been reported after CD19-targeted chimeric antigen receptor-modified (CD19 CAR) T-cell therapy for relapsed/refractory (R/R) chronic lymphocytic leukemia (CLL), yet the factors associated with duration of response in this setting are poorly characterized. We analyzed long-term outcomes in 47 patients with R/R CLL and/or Richter transformation treated on our phase 1/2 clinical trial of CD19 CAR T-cell therapy with an updated median follow-up of 79.6 months. Median progression-free survival (PFS) was 8.9 months, and the 6-year PFS was 17.8%. Maximum standardized uptake value (hazard ratio [HR], 1.15; 95% confidence interval [CI], 1.07-1.23; P < .001) and bulky disease (≥5 cm; HR, 2.12; 95% CI, 1.06-4.26; P = .034) before lymphodepletion were associated with shorter PFS. Day +28 complete response by positron emission tomography-computed tomography (HR, 0.13; 95% CI, 0.04-0.40; P < .001), day +28 measurable residual disease (MRD) negativity by multiparameter flow cytometry (HR, 0.08; 95% CI, 0.03-0.22; P < .001), day +28 MRD negativity by next-generation sequencing (HR, 0.21; 95% CI, 0.08-0.51; P < .001), higher peak CD8+ CAR T-cell expansion (HR, 0.49; 95% CI; 0.36-0.68; P < .001), higher peak CD4+ CAR T-cell expansion (HR, 0.47; 95% CI; 0.33-0.69; P < .001), and longer CAR T-cell persistence (HR, 0.56; 95% CI, 0.44-0.72; P < .001) were associated with longer PFS. The 6-year duration of response and overall survival were 26.4% and 31.2%, respectively. CD19 CAR T-cell therapy achieved durable responses with curative potential in a subset of patients with R/R CLL. This trial was registered at www.clinicaltrials.gov as #NCT01865617.
在接受针对复发/难治性（R/R）慢性淋巴细胞白血病（CLL）的 CD19 靶向嵌合抗原受体修饰（CD19 CAR）T 细胞疗法后，已经报道了高缓解率，但在这种情况下与缓解持续时间相关的因素尚未得到很好的描述。我们分析了在我们的 CD19 CAR T 细胞治疗的 1/2 期临床试验中接受治疗的 47 例 R/R CLL 和/或 Richter 转化患者的长期结局，更新后的中位随访时间为 79.6 个月。中位无进展生存期（PFS）为 8.9 个月，6 年 PFS 为 17.8%。最大标准化摄取值（hazard ratio [HR]，1.15；95%置信区间 [CI]，1.07-1.23；P <.001）和在前淋巴细胞减少治疗前存在大肿块疾病（≥5 cm；HR，2.12；95%CI，1.06-4.26；P =.034）与较短的 PFS 相关。正电子发射断层扫描-计算机断层扫描（PET-CT）检查的 28 天完全缓解（HR，0.13；95%CI，0.04-0.40；P <.001），多参数流式细胞术检查的 28 天可测量残留疾病（MRD）阴性（HR，0.08；95%CI，0.03-0.22；P <.001），下一代测序检查的 28 天 MRD 阴性（HR，0.21；95%CI，0.08-0.51；P <.001），高峰 CD8+ CAR T 细胞扩增更高（HR，0.49；95%CI，0.36-0.68；P <.001），高峰 CD4+ CAR T 细胞扩增更高（HR，0.47；95%CI，0.33-0.69；P <.001）和更长的 CAR T 细胞持久性（HR，0.56；95%CI，0.44-0.72；P <.001）与更长的 PFS 相关。6 年缓解持续时间和总生存率分别为 26.4%和 31.2%。CD19 CAR T 细胞疗法在接受治疗的 R/R CLL 患者亚组中实现了具有治愈潜力的持久缓解。该试验在 www.clinicaltrials.gov 上注册，编号为 #NCT01865617。
