CAR-T(CAR-T)细胞疗法在非肿瘤性疾病中的应用
Chimeric antigen receptor T (CAR-T) cell therapy in non-oncological diseases.
CAR-T(CAR-T)细胞在血液系统恶性肿瘤中的应用推动了这种免疫治疗形式的显著进展。
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Positron emission tomography-imaging assessment for guiding strategy in patients with relapsed/refractory large B-cell lymphoma receiving CAR T cells.
Positron emission tomography-imaging assessment for guiding strategy in patients with relapsed/refractory large B-cell lymphoma receiving CAR T cells.
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本研究在一项多中心队列中,评估复发/难治性大 B 细胞淋巴瘤(R/R LBCL)160 例患者接受抗 CD19 嵌合抗原受体(CAR)T 细胞治疗后 1 个月(M1)和 3 个月(M3)的氟代脱氧葡萄糖正电子发射断层扫描反应的预后影响。共 119 例(75%)患者完成 M1 评估;其中 64 例(53%,64/119)完全缓解(CR),91% 的患者 Deauville 评分(DS)为 1–3。M1 时 DS 为 5 的患者,其无进展生存期(PFS)和总生存期(OS)均显著差于 DS 为 1–3 和 DS 为 4 的患者:与 DS 1–3 相比,PFS 风险比(HR)为 6.37(95% 置信区间 [CI]:3.5–11.5),OS HR 为 3.79(95% CI:1.7–8.5);与 DS 4 相比,PFS HR 为 11.99(95% CI:5.0–28.9),OS HR 为 12.49(95% CI:2.8–55.8)。
M1 时 DS 4 患者的 1 年 PFS 率为 78.9%(95% CI:58.9–89.9),与 DS 1–3 患者的 67.3%(95% CI:51.8–78.8)相近,与 DS 5 患者的 8.6%(95% CI:1.8–22.4)差异明显。DS 4 的 30 例患者中仅 8 例(26%)进展。90 例(57%)患者的 M3 反应可预测 PFS,但区分能力较低(HR=3.28,95% CI:1.5–7.0;P=0.003),且不能预测 OS(HR=0.61,95% CI:0.2–2.3;P=0.45)。基线总代谢肿瘤体积(TMTV)>80 mL 的患者,其 PFS(HR=2.05,95% CI:1.2–3.5;P=0.009)和 OS(HR=4.52,95% CI:2.5–8.1;P<0.001)均差于低 TMTV 患者。多变量分析显示,基线乳酸脱氢酶升高、DS 5 及 M1 时 CAR-T 细胞状态与 PFS 相关;基线乳酸脱氢酶升高、TMTV>80 mL 和 M1 时 DS 5 与 OS 相关。
总之,基线 TMTV 和 M1 时治疗反应可有力预测接受 CAR-T 细胞治疗的 R/R LBCL 患者结局。
The aim of this study was to evaluate the prognostic impact of the F-fluorodeoxyglucose positron emission tomography response at 1 month (M1) and 3 months (M3) after anti-CD19 chimeric antigen receptor (CAR) T-cell therapy in a multicenter cohort of 160 patients with relapsed/refractory large B-cell lymphomas (R/R LBCL). In total, 119 (75%) patients reached M1 evaluation; 64 (53%, 64/119) had a complete response (CR); 91% were Deauville Score (DS) 1-3. Progressionfree survival (PFS) and overall survival (OS) were significantly worse in patients with DS-5 at M1, than in patients with DS 1-3 (PFS hazard ratio [HR]=6. 37, 95% confidence interval [CI]: 3. 5-11. 5 vs. OS HR=3. 79, 95% CI: 1. 7-8. 5) and DS-4 (PFS HR=11. 99, 95% CI: 5. 0-28. 9 vs. OS HR=12. 49, 95% CI: 2. 8-55. 8). The 1-year PFS rates were 78.
9% (95% CI: 58. 9-89. 9) for DS-4 at M1, similar to 67. 3% (95% CI: 51. 8-78. 8) for patients with DS 1-3 at M1, very different to 8. 6% (95% CI: 1. 8-22. 4) for DS-5, respectively. Only eight of 30 (26%) patients with DS-4 progressed. Response at M3 evaluated in 90 (57%) patients was prognostic for PFS with lower discrimination (HR=3. 28, 95% CI: 1. 5-7. 0; P=0. 003) but did not predict OS (HR=0. 61, 95% CI: 0.
2-2. 3; P=0. 45). Patients with a high baseline total metabolic tumor volume (TMTV) >80 mL had worse PFS (HR=2. 05, 95% CI: 1. 2-3. 5; P=0. 009) and OS (HR=4. 52, 95% CI: 2. 5-8. 1; P<0. 001) than patients with low TMTV. Multivariable analyses identified baseline elevated lactate dehydrogenase, DS-5, CAR T cells at M1 for PFS and baseline elevated lactate dehydrogenase, TMTV >80 mL, and DS-5 at M1 for OS.
In conclusion, baseline TMTV and response at M1 strongly predicts outcomes of patients with R/R LBCL undergoing CAR T-cell therapy.
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