Clinical characteristics and survival outcomes of patients with primary central nervous system lymphoma treated with high-dose methotrexate-based polychemotherapy and consolidation therapies

IF 7.6 1区医学 Q1 ONCOLOGY

European Journal of Cancer Pub Date : 2024-10-13 DOI:10.1016/j.ejca.2024.115068

Fleur A. de Groot , Tim J.A. Dekker , Jeanette K. Doorduijn , Stefan Böhringer , Mirian Brink , Ruben A.L. de Groen , Lorraine M. de Haan , F.J. Sherida H. Woei-A-Jin , Troy Noordenbos , Aniko Sijs-Szabo , Mirjam A. Oudshoorn , King H. Lam , Arjan Diepstra , Liane C.J. te Boome , Valeska Terpstra , Lara H. Bohmer , Alina Nicolae , Eduardus F.M. Posthuma , Lianne Koens , Marc F. Durian , Joost S.P. Vermaat

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引用次数: 0

Abstract

Given the rarity of primary central nervous system lymphoma (PCNSL), evaluations of different high-dose methotrexate-(HD-MTX)-based treatment regimens is sparse. This retrospective, multicenter study evaluates clinical characteristics and outcomes (progression-free, overall and disease-specific survival) after five HD-MTX-based polychemotherapeutic regimens and two consolidation therapies. 346 patients with histologically confirmed PCNSL, treated with ≥ 1 cycle HD-MTX-based strategies (≥3g/m²/cycle) were included. The regimens included MATRIX (HD-MTX, HD-AraC, thiotepa, and rituximab), (R)MBVP±HD-AraC (HD-MTX, teniposide/etoposide, carmustine, prednisolone, ± HD-AraC, ± rituximab), (R)MP (HD-MTX, procarbazine, ± rituximab), and a combination of HD-MTX and HD-AraC. The overall response rate after induction was 69 %, 28 % complete remission and progressive disease was observed in 100 (29 %) patients. 126 (36 %) patients received consolidation, including high-dose-BCNU-thiotepa with autologous stem cell transplantation (HD-BCNU-TT/ASCT, n = 59 (17 %)) or whole brain radiotherapy (WBRT, n = 67 (19 %)). Clinical characteristics associated with adverse mortality risk by multivariable prognostication contained age > 60 years (HR 1.61, p = 0.011), elevated LDH (HR 1.75, p = 0.004) and WHO status ≥ 2 (HR 1.56, p = 0.010). Independently, induction regimens containing HD-AraC demonstrated survival benefit compared to induction regimens without HD-AraC (HR 0.59, p = 0.002). Without preference for HD-BCNU-TT/ASCT or WBRT, a favorable effect of consolidation (HR 0.44 and HR 0.42, p < 0.001) was confirmed, also with consolidation as time-dependent variable. Competing risk analysis showed similar low incidence of lymphoma-unrelated deaths in consolidated and unconsolidated patients. This study confirms that age, elevated LDH and WHO status increase the mortality risk. HD-AraC containing treatment regimens and consolidation with HD-BCU-TT/ASCT or WBRT were associated with superior survival, including a favorable low incidence of lymphoma-unrelated deaths.

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以大剂量甲氨蝶呤为基础的多化疗和巩固治疗原发性中枢神经系统淋巴瘤患者的临床特征和生存结果。

鉴于原发性中枢神经系统淋巴瘤（PCNSL）的罕见性，对基于高剂量甲氨蝶呤（HD-MTX）的不同治疗方案的评估很少。这项回顾性多中心研究评估了五种基于 HD-MTX 的多化疗方案和两种巩固治疗后的临床特征和疗效（无进展生存期、总生存期和疾病特异性生存期）。346名经组织学确诊的PCNSL患者接受了≥1个周期的HD-MTX治疗（≥3g/m2/周期）。治疗方案包括MATRIX（HD-MTX、HD-AraC、噻替帕和利妥昔单抗）、(R)MBVP±HD-AraC（HD-MTX、替尼泊苷/依托泊苷、卡莫司汀、泼尼松龙、±HD-AraC、±利妥昔单抗）、(R)MP（HD-MTX、丙卡巴嗪、±利妥昔单抗）以及HD-MTX和HD-AraC联合疗法。诱导治疗后的总体反应率为 69%，完全缓解率为 28%，100 名患者（29%）的病情出现进展。126例（36%）患者接受了巩固治疗，包括高剂量-BCNU-噻替派与自体干细胞移植（HD-BCNU-TT/ASCT，n = 59（17%））或全脑放疗（WBRT，n = 67（19%））。通过多变量预后分析，与不良死亡风险相关的临床特征包括年龄大于 60 岁（HR 1.61，P = 0.011）、LDH 升高（HR 1.75，P = 0.004）和 WHO 状态≥ 2（HR 1.56，P = 0.010）。与不含HD-AraC的诱导方案相比，含HD-AraC的诱导方案可独立显示生存获益（HR 0.59，P = 0.002）。在不优先选择HD-BCNU-TT/ASCT或WBRT的情况下，巩固治疗的有利影响（HR 0.44和HR 0.42，P = 0.010）。

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来源期刊

European Journal of Cancer 医学-肿瘤学

CiteScore

11.50

自引率

4.80%

发文量

953

审稿时长

23 days

期刊介绍： The European Journal of Cancer (EJC) serves as a comprehensive platform integrating preclinical, digital, translational, and clinical research across the spectrum of cancer. From epidemiology, carcinogenesis, and biology to groundbreaking innovations in cancer treatment and patient care, the journal covers a wide array of topics. We publish original research, reviews, previews, editorial comments, and correspondence, fostering dialogue and advancement in the fight against cancer. Join us in our mission to drive progress and improve outcomes in cancer research and patient care.