University of Paris APHP, Saint-Louis Hospital, Hemato-oncology, DMU DHI, Paris, France.
Institut Curie, Paris, France.
Blood. 2022 Dec 15;140(24):2584-2593. doi: 10.1182/blood.2022016945.
Anti-CD19 chimeric antigen receptor (CAR) T-cells represent a major advance in the treatment of relapsed/refractory aggressive B-cell lymphomas. However, a significant number of patients experience failure. Among 550 patients registered in the French registry DESCAR-T, 238 (43.3%) experienced progression/relapse, with a median follow-up of 7.9 months. At registration, 57.0% of patients presented an age-adjusted International Prognostic Index of 2 to 3, 18.9% had Eastern Cooperative Oncology Group performance status ≥2, 57.1% received >3 lines of treatment prior to receiving CAR T-cells, and 87.8% received bridging therapy. At infusion, 66% of patients presented progressive disease, and 38.9% had high lactate dehydrogenase (LDH). Failure after CAR T-cell treatment occurred after a median of 2.7 months (range: 0.2-21.5). Fifty-four patients (22.7%) presented very early failure (day [D] 0-D30); 102 (42.9%) had early failure (D31-D90), and 82 (34.5%) had late (>D90) failure. After failure, 154 patients (64%) received salvage treatment: 38.3% received lenalidomide, 7.1% bispecific antibodies, 21.4% targeted treatment, 11% radiotherapy, and 20% immunochemotherapy with various regimens. Median progression-free survival was 2.8 months, and median overall survival (OS) was 5.2 months. Median OS for patients failing during D0-D30 vs after D30 was 1.7 vs 3.0 months, respectively (P = .0001). Overall, 47.9% of patients were alive at 6 months, but only 18.9% were alive after very early failure. In multivariate analysis, predictors of OS were high LDH at infusion, time to CAR-T failure <D30, and high C-reactive protein at infusion. This multicentric analysis confirms the poor outcome of patients relapsing after CAR T-cell treatment, highlighting the need for further strategies dedicated to this population.
抗 CD19 嵌合抗原受体 (CAR) T 细胞代表了复发/难治性侵袭性 B 细胞淋巴瘤治疗的重大进展。然而，仍有相当数量的患者治疗失败。在法国 DESCAR-T 注册中心登记的 550 名患者中，238 名（43.3%）出现进展/复发，中位随访时间为 7.9 个月。登记时，57.0%的患者年龄调整后的国际预后指数为 2-3，18.9%的患者东部合作肿瘤组体能状态≥2，57.1%的患者在接受 CAR T 细胞治疗前接受了>3 线治疗，87.8%的患者接受了桥接治疗。输注时，66%的患者存在进行性疾病，38.9%的患者乳酸脱氢酶（LDH）升高。CAR T 细胞治疗后中位 2.7 个月（范围：0.2-21.5）发生治疗失败。54 名患者（22.7%）出现早期失败（第 0 天至 30 天）；102 名患者（42.9%）出现早期失败（第 31 天至 90 天），82 名患者（34.5%）出现晚期（>90 天）失败。治疗失败后，154 名患者（64%）接受挽救治疗：38.3%接受来那度胺，7.1%接受双特异性抗体，21.4%接受靶向治疗，11%接受放疗，20%接受不同方案的免疫化疗。中位无进展生存期为 2.8 个月，中位总生存期（OS）为 5.2 个月。0-30 天失败的患者中位 OS 为 1.7 个月，30 天后失败的患者中位 OS 为 3.0 个月（P=.0001）。总体而言，6 个月时 47.9%的患者存活，但仅 18.9%的患者在早期失败后存活。多变量分析显示，OS 的预测因素为输注时高乳酸脱氢酶、CAR-T 失败时间<30 天和输注时高 C 反应蛋白。这项多中心分析证实了 CAR T 细胞治疗后复发患者的预后较差，强调需要针对这一人群制定进一步的策略。
