Dataset Information

First-line induction chemotherapy with high-dose methotrexate versus teniposide in patients with newly diagnosed primary central nervous system lymphoma: a retrospective, multicenter cohort study.

ABSTRACT:

Background

This study aimed to compare the efficacy and safety of high-dose methotrexate (HD-MTX) versus teniposide (TEN) in patients with newly diagnosed immunocompetent primary central nervous system lymphomas (PCNSLs).

Methods

The study included immunocompetent, adult patients with newly diagnosed PCNSL at 22 centers in China from 2007 to 2016. The patients received HD-MTX or TEN as first-line induction therapy. The objective response rate, progression-free survival, and overall survival were analyzed for each patient cohort.

Results

A total of 96 patients were eligible: 62 received HD-MTX, while 34 received teniposide. The overall response rate was 73.2% and 72.7% in the MTX and the TEN cohorts, respectively (P = 0.627). The median progression-free survival was 28.4 months [95% confidence interval (CI): 13.7-51.2] in the MTX cohort and 24.3 months (95% CI: 16.6-32.1) in the TEN cohort (P = 0.75). The median overall survival was 31 months (95% CI: 26.8-35.2) in the MTX cohort and 32 months (95% CI: 27.6-36.4) in the TEN cohort (P = 0.77). The incidence of any grade of coagulopathy/deep-vein thrombosis and gastrointestinal disorders was significantly higher in the MTX cohort than in the TEN cohort; no significant difference was found in the incidence of other adverse events between the two cohorts.

Conclusions

This was the first multicenter study using TEN as the main agent compared with HD-MTX in newly diagnosed primary CNS lymphoma. The TEN-based regimen was non-inferior to the HD-MTX-based regimen with similar overall responses.

Classification of evidence

This study provided Class III evidence that the teniposide-based regimen was non-inferior to high-dose methotrexate - based regimen with similar overall responses and long-time survival in immunocompetent patients with PCNSL.

SUBMITTER: Zhong K

PROVIDER: S-EPMC10416388 | biostudies-literature | 2023 Aug

REPOSITORIES: biostudies-literature

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Publications

First-line induction chemotherapy with high-dose methotrexate versus teniposide in patients with newly diagnosed primary central nervous system lymphoma: a retrospective, multicenter cohort study.

Zhong Kaili K Shi Yanyan Y Gao Yuhuan Y Zhang Huilai H Zhang Mingzhi M Zhang Qiaohua Q Cen Xinan X Xue Mei M Qin Yan Y Zhao Yu Y Zhang Liling L Liang Rong R Wang Ningju N Xie Yan Y Yang Yu Y Liu Aichun A Bao Huizheng H Wang Jingwen J Cao Baoping B Zhang Wei W Zhang Weijing W

BMC cancer 20230811 1

<h4>Background</h4>This study aimed to compare the efficacy and safety of high-dose methotrexate (HD-MTX) versus teniposide (TEN) in patients with newly diagnosed immunocompetent primary central nervous system lymphomas (PCNSLs).<h4>Methods</h4>The study included immunocompetent, adult patients with newly diagnosed PCNSL at 22 centers in China from 2007 to 2016. The patients received HD-MTX or TEN as first-line induction therapy. The objective response rate, progression-free survival, and overal ...[more]

PMID: 37568079

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Project description:BackgroundThis study aimed to comprehensively assess the optimal regimen for high-dose methotrexate (HD-MTX) in treating primary central nervous system lymphoma (PCNSL).MethodsWe have searched 8 databases, including PubMed, EMBASE, Cochrane Library, WOS, Epistemonikos, CNKI, WAN-FANG Database, and CBM, and were selected for the clinical trials about PCNSL. A total of 37 studies were included in our analysis, consisting of 6 randomized controlled trials and 31 single-arm clinical studies.ResultsAfter analyzing the data from 37 clinical studies, we found that the pooled overall response rate (ORR) for low-dose (<3 g/m2), medium-dose (3-5 g/m2), and high-dose (>5 g/m2) methotrexate (MTX) were 0.78, 0.80, and 0.80, respectively. The pooled 2-year overall survival (OS) for low-dose, medium-dose, and high-dose MTX were 52%, 60%, and 71%, respectively. The ORR, complete response (CR), and 2-year OS of patients who received <5 cycles of MTX were 79%, 41%, and 59%, respectively, whereas those for PCNSL patients who received >5 cycles of MTX were 81%, 54%, and 64%, respectively. The pooled ORR for MTX, dual therapy, triplet therapy, tetrad therapy, and multiple therapy were 71%, 70%, 81%, 85%, and 80%, respectively. The pooled 2-year OS for different numbers of medication combinations were 59%, 52%, 66%, 63%, and 60%, respectively. The addition of cytarabine to MTX-based chemotherapy resulted in higher CR, although no statistically significant difference was observed in OS. Adding rituximab to the treatment regimen improved patients' progression-free survival without affecting treatment response or OS.ConclusionBased on the findings of this study, the treatment strategies of MTX are associated with the prognosis and efficacy response of PCNSL patients. The results suggested that the current recommended HD-MTX dosage of 3.5 g/m2 is sufficient for PCNSL to have a favorable treatment response and prognosis. When the number of MTX treatment cycles increases, the therapeutic effect and prognosis of PCNSL patients are improved. The patients treated with MTX-based triplet combination regimens have a better ORR and CR. Although HD-MTX is generally well tolerated, it is necessary to be cautious about the use of multiple therapy that includes cytarabine to prevent potential acute toxicity.

Project description:BackgroundPrimary diffuse large B-cell lymphoma (DLBCL) of the central nervous system (PCNSL) is a rare disorder with an increasing incidence over the past decades. High-level evidence has been reported for the MATRix regimen (high-dose methotrexate (HD-MTX), high-dose AraC (HD-AraC), thiotepa and rituximab) followed by high-dose chemotherapy and autologous stem cell transplantation (HCT-ASCT) supporting this approach to be considered a standard therapy in newly diagnosed PCNSL patients ≤ 70 years. However, early treatment-related toxicities (predominantly infectious complications), occurring in up to 28% per MATRix cycle, diminish its therapeutic success. Furthermore, sensitivity to first-line treatment is an independent prognostic factor for improved overall survival (OS) in PCNSL. Thus, patients achieving early partial remission (PR) after 2 cycles of MATRix might be over-treated with 4 cycles, in the context of consolidation HCT-ASCT.MethodsThis is an open-label, multicentre, randomized phase III trial with two parallel arms. 326 immunocompetent patients with newly diagnosed PCNSL will be recruited from 37 German, 1 Austrian and 12 UK sites. Additional IELSG (International Extranodal Lymphoma Study Group) sites are planned. The objective is to demonstrate superiority of a de-escalated and optimised remission induction treatment strategy, followed by HCT-ASCT. Randomization (1:1) will be performed after completion of all screening procedures. Patients in Arm A (control treatment) will receive 4 cycles of MATRix. Patients in Arm B (experimental treatment) will receive a pre-phase (R/HD-MTX), followed by 2 cycles of MATRix. Patients in both arms achieving PR or better will proceed to HCT-ASCT (BCNU, thiotepa). The primary endpoint of the study is event-free-survival (EFS), defined as time from randomization to premature end of treatment due to any reason, lymphoma progression or death whichever occurs first. Secondary endpoints include OS, progression free survival (PFS), toxicity, neurocognitive impairment and quality of life. Minimal follow-up is 24 months.DiscussionCurrent treatment options for PCNSL in patients ≤ 70 years have improved remarkably over recent years. However, the potential efficacy benefits are offset by an increased incidence of short-term toxicities which can impact on treatment delivery and hence on survival outcomes. In patients ≤ 70 years with newly diagnosed PCNSL addressing the need to reduce treatment-related toxicity by de-escalating and optimising the induction phase of treatment, is a potentially attractive treatment strategy.Trial registrationGerman clinical trials registry DRKS00022768 registered June 10th, 2021.

Dataset Information

First-line induction chemotherapy with high-dose methotrexate versus teniposide in patients with newly diagnosed primary central nervous system lymphoma: a retrospective, multicenter cohort study.

Background

Methods

Results

Conclusions

Classification of evidence

Publications

First-line induction chemotherapy with high-dose methotrexate versus teniposide in patients with newly diagnosed primary central nervous system lymphoma: a retrospective, multicenter cohort study.

Similar Datasets

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