National Institutes of Health (NIH)/National Heart, Lung, and Blood Institute Medical Oncology/Hematology Fellowship Program, Bethesda, MD.
Surgery Branch, Center for Cancer Research, National Cancer Istitute, NIH, Bethesda, MD.
J Clin Oncol. 2020 Nov 10;38(32):3805-3815. doi: 10.1200/JCO.20.01467. Epub 2020 Oct 6.
Anti-CD19 chimeric antigen receptors (CARs) are artificial fusion proteins that cause CD19-specific T-cell activation. Durability of remissions and incidence of long-term adverse events are critical factors determining the utility of anti-CD19 CAR T-cell therapy, but long-term follow-up of patients treated with anti-CD19 CAR T cells is limited. This work provides the longest follow-up of patients in remission after anti-CD19 CAR T-cell therapy.
Between 2009 and 2015, we administered 46 CAR T-cell treatments to 43 patients (ClinicalTrials.gov identifier: NCT00924326). Patients had relapsed B-cell malignancies of the following types: diffuse large B-cell lymphoma or primary mediastinal B-cell lymphoma (DLBCL/PMBCL; n = 28), low-grade B-cell lymphoma (n = 8), or chronic lymphocytic leukemia (CLL; n = 7). This report focuses on long-term outcomes of these patients. The CAR used was FMC63-28Z; axicabtagene ciloleucel uses the same CAR. Cyclophosphamide plus fludarabine conditioning chemotherapy was administered before CAR T cells.
The percentages of CAR T-cell treatments resulting in a > 3-year duration of response (DOR) were 51% (95% CI, 35% to 67%) for all evaluable treatments, 48% (95% CI, 28% to 69%) for DLBCL/PMBCL, 63% (95% CI, 25% to 92%) for low-grade lymphoma, and 50% (95% CI, 16% to 84%) for CLL. The median event-free survival of all 45 evaluable treatments was 55 months. Long-term adverse effects were rare, except for B-cell depletion and hypogammaglobulinemia. Median peak blood CAR-positive cell levels were higher among patients with a DOR of > 3 years (98/µL; range, 9-1,217/µL) than among patients with a DOR of < 3 years (18/µL; range, 0-308/μL, = .0051).
Complete remissions of a variety of B-cell malignancies lasting ≥ 3 years occurred after 51% of evaluable anti-CD19 CAR T-cell treatments. Remissions of up to 9 years are ongoing. Late adverse events were rare.
抗 CD19 嵌合抗原受体（CARs）是一种人工融合蛋白，可导致 CD19 特异性 T 细胞激活。缓解的持久性和长期不良事件的发生率是决定抗 CD19 CAR T 细胞治疗效用的关键因素，但接受抗 CD19 CAR T 细胞治疗的患者的长期随访受到限制。本研究提供了接受抗 CD19 CAR T 细胞治疗后缓解患者的最长随访结果。
2009 年至 2015 年，我们对 43 名患者（ClinicalTrials.gov 标识符：NCT00924326）进行了 46 次 CAR T 细胞治疗。患者患有以下类型的复发 B 细胞恶性肿瘤：弥漫性大 B 细胞淋巴瘤或原发性纵隔 B 细胞淋巴瘤（DLBCL/PMBCL；n=28）、低级别 B 细胞淋巴瘤（n=8）或慢性淋巴细胞白血病（CLL；n=7）。本报告重点介绍这些患者的长期结果。使用的 CAR 是 FMC63-28Z；axi-cabtagene ciloleucel 使用相同的 CAR。在 CAR T 细胞之前，给予环磷酰胺加氟达拉滨预处理化疗。
所有可评估治疗中，CAR T 细胞治疗产生 > 3 年缓解持续时间（DOR）的百分比为 51%（95%CI，35%至 67%），DLBCL/PMBCL 为 48%（95%CI，28%至 69%），低级别淋巴瘤为 63%（95%CI，25%至 92%），CLL 为 50%（95%CI，16%至 84%）。45 次可评估治疗的中位无事件生存时间为 55 个月。除 B 细胞耗竭和低丙种球蛋白血症外，长期不良事件罕见。DOR > 3 年的患者中位血 CAR 阳性细胞水平较高（98/µL；范围，9-1,217/µL），而 DOR < 3 年的患者中位血 CAR 阳性细胞水平较低（18/µL；范围，0-308/µL， =.0051）。
51%的可评估抗 CD19 CAR T 细胞治疗后，各种 B 细胞恶性肿瘤完全缓解持续时间≥3 年。缓解持续时间长达 9 年仍在继续。迟发性不良事件罕见。
