背景:CAR-T细胞疗法被批准用于治疗复发性/难治性(R/R)大B细胞淋巴瘤(LBCL)。然而,由于其毒性,老年患者可能不是这种疗法的候选人,缺乏候选人选择的标准。我们的目的是分析70岁及以上人群中CAR-T细胞疗法的疗效和毒性结果,与现实世界中年轻患者相比。
方法:进行了一项多中心回顾性研究,包括R/R侵袭性LBCL患者,他们在西班牙GETH-TC/GELTAMO中心接受了商业CAR-T细胞治疗,使用tisagenlecleucel或axicabtageneciloleucel。2019年至2023年。
结果:截至2023年8月,442名患有侵袭性LBCL的成年患者接受了CAR-T细胞疗法的单采术作为第三行或后续行,并获得了随访数据。412名输液病人中,71(17%)岁以上。基线特征,单采术的产品选择和特征(包括疾病状态,安阿伯舞台,R-IPI,庞大的疾病,LDH和ECOG)在组间具有可比性。从批准到输注和单采到输注的中位时间没有差异。在1个月和3个月时,两组之间的总体和完全缓解率没有差异。中位随访时间为12.2个月(范围1-44),两组之间的12个月无进展生存期(PFS)和总生存期(OS)具有可比性(<70岁时35.2%与≥70y的35.9%(p=p=0.938)和51.1%和52.1%(p=p=0.885),分别)。在单变量和多变量分析中,年龄≥70岁不影响PFS(HR0.98,p=0.941)和OS(HR0.97,p=0.890)。在<70y的82%患者中观察到细胞因子释放综合征(CRS),在≥70y的患者中观察到84.5%(p=0.408)。≥3级CRS在老年组中更常见(5%与15%,p=0.002)。在多变量分析中,年龄≥70岁与≥3级CRS风险增加相关(OR3.7,p=0.013).在总体神经毒性方面没有观察到差异(35%vs.42%,p=0.281)或≥3级(12%与17%,p=0.33)。感染患者的比例,两组在1个月内入住重症监护病房和非复发死亡率相似.
结论:CAR-T细胞疗法在70岁以上患者中的疗效与在现实世界中年轻患者中的疗效相似。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,应解决减少该人群毒性的其他策略的需求。
BACKGROUND: 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 70 years and older as compared to those obtained in younger patients in the real-world setting.
METHODS: 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 Spanish GETH-TC/GELTAMO centers between 2019 and 2023.
RESULTS: As of August 2023, 442 adult patients with aggressive LBCL underwent apheresis for CAR-T cell therapy as third or subsequent line and had follow-up data. 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, R-IPI, bulky disease, LDH and ECOG) 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 one and three 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 <70y vs. 35.9% in ≥70y (p= p=0.938) and 51.1% and 52.1% (p= p=0.885), respectively). Age ≥70 years did not affect PFS (HR 0.98, p=0.941) and OS (HR 0.97, p=0.890) in the univariate and multivariate analysis. Cytokine release syndrome (CRS) was observed in 82% patients in <70y and 84.5% in ≥70y (p=0.408). Grade ≥3 CRS was more frequent in the older group (5% vs. 15%, p=0.002). In the multivariate analysis, age ≥70y was associated with an increased risk of grade ≥3 CRS (OR 3.7, p=0.013). No differences were observed in terms of overall neurotoxicity (35% vs. 42%, p=0.281) or grade ≥3 (12% vs. 17%, p=0.33). The proportion of patients with infections, admission to intensive care unit within the first month and non-relapse mortality were similar between both groups.
CONCLUSIONS: CAR-T cell therapy in patients older than 70 years showed similar efficacy than that observed in younger patients in the real-world setting. However, age ≥70 years was an independent risk factor for grade 3-4 CRS. Need of additional strategies to reduce toxicity in this population should be addressed in future studies.