背景:对于患有原发性弥漫性大B细胞CNS淋巴瘤(PCNSL)的老年患者,可用的治疗方法可提供长达16个月的无进展生存期。我们旨在研究大剂量化疗和自体造血干细胞移植(HSCT)对老年PCNSL患者的强化治疗。
方法:MARTA是一个前瞻性的,单臂,在德国15家研究型医院进行的第二阶段研究。65岁或以上新诊断的患者,如果他们的东部肿瘤协作组表现状态为0-2,并且适合大剂量化疗和自体HSCT,则未治疗的PCNSL被纳入。诱导治疗包括两个21天周期的大剂量静脉注射甲氨蝶呤3·5g/m2(第1天),静脉注射阿糖胞苷2g/m2每天两次(第2天和第3天),和静脉注射利妥昔单抗375mg/m2(第0天和第4天),然后大剂量化疗与静脉注射利妥昔单抗375mg/m2(第-8天),静脉注射白消安3·2mg/kg(第-7和-6天),和静脉注射噻替帕5mg/kg(第-5天和第-4天)加自体HSCT。主要终点是所有符合资格标准并开始治疗的患者在12个月时的无进展生存期。这项研究在德国临床试验注册中心注册,DRKS00011932,招聘完成。
结果:在2017年11月28日至2020年9月16日之间,54例患者开始诱导治疗,51例患者被纳入完整分析集。中位年龄为71岁(IQR68-75);27(53%)患者为女性,24(47%)为男性。中位随访时间为23·0个月(IQR16·8-37·4),51例患者中有23例(45%)进展,复发,或死亡。12个月无进展生存率为58·8%(80%CI48·9-68·2;95%CI44·1-70·9)。在诱导治疗期间,最常见的3~5级毒性反应是血小板减少和白细胞减少(54例患者中有52例[96%]).在大剂量化疗和自体HSCT期间,最常见的3~5级毒性是白细胞减少症(37例患者中的37例[100%]).54例患者中有3例(6%)报告了与治疗相关的死亡,都是因为感染并发症.
结论:尽管未达到主要疗效阈值,在选定的老年PCNSL患者中,短期诱导后再进行大剂量化疗和自体HSCT是活跃的,可以作为比较试验的基准.
背景:ElseKröner-Fresenius基金会,RiemserPharma,医学中心-弗莱堡大学。
BACKGROUND: Available treatments for older patients with primary diffuse large B-cell CNS lymphoma (PCNSL) offer progression-free survival of up to 16 months. We aimed to investigate an intensified treatment of high-dose chemotherapy and autologous haematopoietic stem-cell transplantation (HSCT) in older patients with PCNSL.
METHODS: MARTA was a prospective, single-arm, phase 2
study done at 15 research hospitals in Germany. Patients aged 65 years or older with newly diagnosed, untreated PCNSL were enrolled if they had an Eastern Cooperative Oncology Group performance status of 0-2 and were fit for high-dose chemotherapy and autologous HSCT. Induction treatment consisted of two 21-day cycles of high-dose intravenous methotrexate 3·5 g/m2 (day 1), intravenous cytarabine 2 g/m2 twice daily (days 2 and 3), and intravenous rituximab 375 mg/m2 (days 0 and 4) followed by high-dose chemotherapy with intravenous rituximab 375 mg/m2 (day -8), intravenous busulfan 3·2 mg/kg (days -7 and -6), and intravenous thiotepa 5 mg/kg (days -5 and -4) plus autologous HSCT. The primary endpoint was progression-free survival at 12 months in all patients who met eligibility criteria and started treatment. The
study was registered with the German clinical
trial registry, DRKS00011932, and recruitment is complete.
RESULTS: Between Nov 28, 2017, and Sept 16, 2020, 54 patients started induction treatment and 51 were included in the full analysis set. Median age was 71 years (IQR 68-75); 27 (53%) patients were female and 24 (47%) were male. At a median follow-up of 23·0 months (IQR 16·8-37·4), 23 (45%) of 51 patients progressed, relapsed, or died. 12-month progression-free survival was 58·8% (80% CI 48·9-68·2; 95% CI 44·1-70·9). During induction treatment, the most common grade 3-5 toxicities were thrombocytopenia and
leukopenia (each in 52 [96%] of 54 patients). During high-dose chemotherapy and autologous HSCT, the most common grade 3-5 toxicity was
leukopenia (37 [100%] of 37 patients). Treatment-related deaths were reported in three (6%) of 54 patients, all due to infectious complications.
CONCLUSIONS: Although the primary efficacy threshold was not met, short induction followed by high-dose chemotherapy and autologous HSCT is active in selected older patients with PCNSL and could serve as a benchmark for comparative trials.
BACKGROUND: Else Kröner-Fresenius Foundation, Riemser Pharma, and Medical Center-University of Freiburg.