Long-Term Outcomes From a Randomized Dose Optimization Study of Chimeric Antigen Receptor Modified T Cells in Relapsed Chronic Lymphocytic Leukemia
Long-Term Outcomes From a Randomized Dose Optimization Study of Chimeric Antigen Receptor Modified T Cells in Relapsed Chronic Lymphocytic Leukemia
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DOI：
10.1200/jco.19.03237
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发表时间：
2020-09-01
影响因子：
45.3
通讯作者：
Porter, David L.
中科院分区：
文献类型：
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作者：
Frey, Noelle, V;Gill, Saar;Porter, David L.
目的描述抗CD 19嵌合抗原受体T（CART）细胞治疗复发或难治性慢性淋巴细胞白血病（CLL）患者的长期疗效。方法2013年1月至2016年6月，42例复发或难治性CLL患者入组本研究，其中38例接受抗CD 19 CART细胞（CART-19）输注。其中，28名患者最初被随机分配接受低剂量（5 × 10（7））或高剂量（5 × 10（8））的CART-19，24名患者可进行反应评估。在中期分析后，另外10名患者接受了选定的（高）剂量，其中8名患者的反应可评价。患者随访时间中位数为31.5个月（范围：2 - 75个月）。结果4周时，32例可评价患者的完全缓解率和总体缓解率分别为28%（90%CI，16%至44%）和44%（90%CI，29%至60%）。所有患者的中位总生存期（OS）为64个月;低剂量组和高剂量组之间无统计学显著差异（P= 0.84）。无论剂量如何，在达到CR的患者中观察到生存期延长，而在未达到CR的患者中观察到生存期延长（P= 0.035），CR患者未达到中位OS，而未达到CR的患者为64个月。CR患者的中位无进展生存期为40.2个月，未CR患者为1个月（P<0.0001）。两个剂量组的毒性相当。结论在晚期CLL患者中，5 × 10（8）剂量的CART-19可能比5 × 10（7）剂量的CART-19更有效地诱导CR，而不会产生过度毒性。CART-19输注后达到CR，无论细胞剂量如何，与复发性CLL患者的OS和无进展生存期延长相关。
PURPOSE To describe long-term outcomes of anti-CD19 chimeric antigen receptor T (CART) cells in patients with relapsed or refractory chronic lymphocytic leukemia (CLL). METHODS Between January 2013 and June 2016, 42 patients with relapsed or refractory CLL were enrolled in this study and 38 were infused with anti-CD19 CART cells (CART-19). Of these, 28 patients were initially randomly assigned to receive a low (5 x 10(7)) or high (5 x 10(8)) dose of CART-19, and 24 were evaluable for response assessment. After an interim analysis, 10 additional patients received the selected (high) dose and of these, eight were evaluable for response. Patients were followed for a median 31.5 months (range, 2 to 75 months). RESULTS At 4 weeks, the complete and overall responses for the 32 evaluable patients were 28% (90% CI, 16% to 44%) and 44% (90% CI, 29% to 60%), respectively. The median overall survival (OS) for all patients was 64 months; there was no statistically significant difference between low- and high-dose groups (P= .84). Regardless of dose, prolonged survival was observed in patients who achieved a CR versus those who did not (P= .035), with median OS not reached in patients with CR versus 64 months in those without CR. The median progression-free survival was 40.2 months in patients with CR and 1 month in those without a CR (P< .0001). Toxicity was comparable in both dose groups. CONCLUSION In patients with advanced CLL, a 5 x 10(8)dose of CART-19 may be more effective than 5 x 10(7)CART-19 at inducing CR without excessive toxicity. Attainment of a CR after CART-19 infusion, regardless of cell dose, is associated with longer OS and progression-free survival in patients with relapsed CLL.