Department of Hematology, Hospital General Universitario Gregorio Marañón, Madrid, Spain.; Gregorio Marañón Health Research Institute, Madrid, Spain.
Department of Hematology, Vall d'Hebron University Hospital, Experimental Hematology, Vall d'Hebron Institute of Oncology (VHIO), Barcelona, Spain.; Department of Medicine, Universitat Autònoma de Barcelona, Bellaterra, Spain.
Transplant Cell Ther. 2024 Oct;30(10):988.e1-988.e11. doi: 10.1016/j.jtct.2024.06.022. Epub 2024 Jul 26.
Chimeric antigen receptor (CAR)-T cell therapy is approved for the treatment of relapsed/refractory (R/R) large B cell lymphoma (LBCL). However, elderly patients might not be candidates for this therapy due to its toxicity, and criteria for candidate selection are lacking. Our aim was to analyze efficacy and toxicity results of CAR-T cell therapy in the population of patients 70 years and older as compared to those obtained in younger patients in the real-world setting. A multicentric retrospective study was performed including patients with R/R aggressive LBCL who received commercial CAR-T cell therapy with either tisagenlecleucel or axicabtagene ciloleucel within the Spanish Group of Hematopoietic Transplant and Cell Therapy/Spanish Group of Lymphomas and Autologous Transplant (GETH-TC/GELTAMO) centers between 2019 and 2023. As of August 2023, 442 adult patients with aggressive LBCL underwent apheresis for CAR-T cell therapy as third or subsequent line and follow-up data was collected. Of 412 infused patients, 71 (17%) were 70 years or older. Baseline characteristics, product selection, and characteristics at apheresis (including disease status, Ann Arbor stage, revised international prognosis index (R-IPI), bulky disease, lactate dehydrogenase [LDH] and ECOG [Eastern Cooperative Group performance status]) were comparable between groups. Median time from both approval to infusion and apheresis to infusion did not differ. No differences were found between groups in overall and complete response rates at 1 and 3 months. With a median follow-up of 12.2 months (range 1-44), 12-month progression-free survival (PFS) and overall survival (OS) were comparable between groups (35.2% in <70 years vs. 35.9% in ≥70 years (P = .938) and 51.1% and 52.1% (P = .885), respectively). Age ≥70 years did not affect PFS (hazard ratio (HR) 0.98, P = .941) and OS (HR 0.97, P = .890) in the univariate and multivariate analysis. Cytokine release syndrome (CRS) was observed in 82% of patients <70 years old and 84.5% in ≥ 70 years old (P = .408). Grade ≥3 CRS was more frequent in the older group (5% vs. 15%, P = .002). In the multivariate analysis, age ≥70 years was associated with an increased risk of grade ≥3 CRS (OR 3.7, P = .013). No differences were observed in terms of overall neurotoxicity (35% vs. 42%, P = .281) or grade ≥3 (12% vs. 17%, P = .33). The proportion of patients with infections, admission to the intensive care unit within the first month, and non-relapse mortality were similar between both groups. CAR-T cell therapy in patients older than 70 years showed similar efficacy to that observed in younger patients in the real-world setting. However, age ≥70 years was an independent risk factor for grades 3-4 CRS. The need for additional strategies to reduce toxicity in this population should be addressed in future studies.
嵌合抗原受体 (CAR)-T 细胞疗法已获批用于治疗复发/难治性 (R/R) 大 B 细胞淋巴瘤 (LBCL)。然而,由于其毒性,老年患者可能不符合该疗法的条件,并且缺乏候选者选择标准。我们的目的是分析在真实环境中,与年轻患者相比,70 岁及以上患者接受 CAR-T 细胞疗法的疗效和毒性结果。进行了一项多中心回顾性研究,纳入了在 2019 年至 2023 年期间在西班牙造血移植和细胞治疗组/西班牙淋巴瘤和自体移植组 (GETH-TC/GELTAMO) 中心接受商业 CAR-T 细胞疗法治疗 R/R 侵袭性 LBCL 的患者。截至 2023 年 8 月,442 名侵袭性 LBCL 成年患者接受了 CAR-T 细胞治疗的单采术,作为三线或后续治疗,并收集了随访数据。在 412 名输注患者中,71 名(17%)年龄在 70 岁或以上。两组间基线特征、产品选择和单采时的特征(包括疾病状态、安阿伯分期、修订后的国际预后指数 (R-IPI)、肿块疾病、乳酸脱氢酶 [LDH] 和 ECOG [东部合作组表现状态])相当。从批准到输注和单采到输注的中位时间无差异。两组在 1 个月和 3 个月时的总反应率和完全反应率无差异。在中位随访 12.2 个月(范围 1-44)时,两组间 12 个月无进展生存期 (PFS) 和总生存期 (OS) 无差异(<70 岁组为 35.2%,≥70 岁组为 35.9%(P=0.938)和 51.1%和 52.1%(P=0.885))。年龄≥70 岁在单因素和多因素分析中均不影响 PFS(危险比 (HR) 0.98,P=0.941)和 OS(HR 0.97,P=0.890)。<70 岁组中 82%的患者发生细胞因子释放综合征 (CRS),≥70 岁组中 84.5%的患者发生 CRS(P=0.408)。老年组中更频繁发生≥3 级 CRS(5% vs. 15%,P=0.002)。在多因素分析中,年龄≥70 岁与≥3 级 CRS 的风险增加相关(OR 3.7,P=0.013)。两组间总体神经毒性(35% vs. 42%,P=0.281)或≥3 级(12% vs. 17%,P=0.33)无差异。两组间感染、第一个月入住重症监护病房和非复发死亡率的患者比例相似。在真实环境中,年龄>70 岁的患者接受 CAR-T 细胞疗法的疗效与年轻患者相似。然而,年龄≥70 岁是 3-4 级 CRS 的独立危险因素。在未来的研究中,应探讨减少该人群毒性的额外策略。
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