Identification, risk factors, and clinical course of CNS relapse in DLBCL patients across 19 prospective phase 2 and 3 trials—a LYSA and GLA/ DSHNHL collaboration

IF 12.8 1区医学 Q1 HEMATOLOGY

Leukemia Pub Date : 2024-08-16 DOI:10.1038/s41375-024-02371-y

Fabian Frontzek, Loïc Renaud, Ulrich Dührsen, Viola Poeschel, Sophie Bernard, Loïc Chartier, Nicolas Ketterer, Christian Récher, Olivier Fitoussi, Gerhard Held, Olivier Casasnovas, Corinne Haioun, Nicolas Mounier, Hervé Tilly, Franck Morschhauser, Steven Le Gouill, Imke E. Karsten, Gerben Duns, Christian Steidl, David W. Scott, Wolfram Klapper, Andreas Rosenwald, German Ott, Thierry Molina, Georg Lenz, Marita Ziepert, Bettina Altmann, Catherine Thieblemont, Norbert Schmitz

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Abstract

Progression or relapse in the central nervous system (CNS) remains a rare but mostly fatal event for patients with diffuse large B-cell lymphoma (DLBCL). In a retrospective analysis of 5189 patients treated within 19 prospective German and French phase 2/3 trials, we identified 159 patients experiencing a CNS event (relapse: 62%, progression: 38%). Intracerebral, meningeal, intraspinal, or combined involvement was reported in 44%, 31%, 3%, and 22% of patients, respectively. 62 of 155 evaluable patients (40%) showed concurrent systemic progression/ relapse. 82% of all CNS events occurred within two years after study inclusion or randomization. 87% of patients showed extranodal involvement outside the CNS. Patients generally had poor outcomes with a median overall survival (OS) of 3.4 months (95% CI 2.9–4.2) and a 2-year OS of 15% (10–22%). Outcomes did not differ depending on the site or time point of CNS events. Patients with isolated CNS events demonstrated significantly better OS (p = 0.023). Twenty-five patients were consolidated with autologous or allogeneic stem cell transplantation and achieved a 3-year OS of 36% (20–66%). This large study including more than 5000 DLBCL patients highlights the unmet medical need to improve the outcome of DLBCL patients suffering from CNS relapse.

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19项前瞻性2期和3期试验中DLBCL患者中枢神经系统复发的识别、风险因素和临床过程--LYSA和GLA/DSHNHL合作项目

对于弥漫大 B 细胞淋巴瘤（DLBCL）患者来说，中枢神经系统（CNS）的进展或复发仍然罕见，但大多是致命的。在对19项德国和法国前瞻性2/3期试验中接受治疗的5189名患者进行的回顾性分析中，我们发现159名患者出现了中枢神经系统事件（复发：62%，进展：38%）。脑内、脑膜、椎管内或合并受累的患者比例分别为 44%、31%、3% 和 22%。在 155 例可评估的患者中，62 例（40%）同时出现全身进展/复发。82%的中枢神经系统事件发生在纳入研究或随机分配后两年内。87%的患者出现中枢神经系统以外的结节外受累。患者的预后普遍较差，中位总生存期（OS）为3.4个月（95% CI为2.9-4.2），2年OS为15%（10-22%）。中枢神经系统事件发生的部位或时间点不同，结果也不尽相同。发生孤立中枢神经系统事件的患者的 OS 明显更好（p = 0.023）。25名患者接受了自体或异体干细胞移植，3年生存率为36%（20-66%）。这项包括5000多名DLBCL患者的大型研究强调，改善中枢神经系统复发的DLBCL患者预后的医疗需求尚未得到满足。

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来源期刊

Leukemia 医学-血液学

CiteScore

18.10

自引率

3.50%

发文量

270

审稿时长

3-6 weeks

期刊介绍： Title: Leukemia Journal Overview: Publishes high-quality, peer-reviewed research Covers all aspects of research and treatment of leukemia and allied diseases Includes studies of normal hemopoiesis due to comparative relevance Topics of Interest: Oncogenes Growth factors Stem cells Leukemia genomics Cell cycle Signal transduction Molecular targets for therapy And more Content Types: Original research articles Reviews Letters Correspondence Comments elaborating on significant advances and covering topical issues