Frontzek Fabian, Renaud Loïc, Dührsen Ulrich, Poeschel Viola, Bernard Sophie, Chartier Loïc, Ketterer Nicolas, Récher Christian, Fitoussi Olivier, Held Gerhard, Casasnovas Olivier, Haioun Corinne, Mounier Nicolas, Tilly Hervé, Morschhauser Franck, Le Gouill Steven, Karsten Imke E, Duns Gerben, Steidl Christian, Scott David W, Klapper Wolfram, Rosenwald Andreas, Ott German, Molina Thierry, Lenz Georg, Ziepert Marita, Altmann Bettina, Thieblemont Catherine, Schmitz Norbert
Centre for Lymphoid Cancer, BC Cancer, Vancouver, BC, Canada.
Department of Medicine A, Hematology, Oncology, and Pneumonology, University Hospital of Münster, Münster, Germany.
Leukemia. 2024 Oct;38(10):2225-2234. doi: 10.1038/s41375-024-02371-y. Epub 2024 Aug 16.
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.
对于弥漫性大B细胞淋巴瘤（DLBCL）患者而言，中枢神经系统（CNS）进展或复发仍然是一种罕见但大多致命的事件。在一项对19项德国和法国前瞻性2/3期试验中治疗的5189例患者的回顾性分析中，我们确定了159例发生CNS事件的患者（复发：62%，进展：38%）。分别有44%、31%、3%和22%的患者报告有脑内、脑膜、脊髓内或合并受累。155例可评估患者中有62例（40%）同时出现全身进展/复发。所有CNS事件的82%发生在纳入研究或随机分组后的两年内。87%的患者在CNS外有结外受累。患者的总体预后通常较差，中位总生存期（OS）为3.4个月（95%CI 2.9 - 4.2），2年总生存率为15%（10 - 22%）。预后并不因CNS事件的部位或时间点而有所不同。孤立性CNS事件的患者总生存期显著更好（p = 0.023）。25例患者接受了自体或异基因干细胞移植巩固治疗，3年总生存率为36%（20 - 66%）。这项纳入了5000多名DLBCL患者 的大型研究凸显了改善患有CNS复发的DLBCL患者预后这一未满足的医疗需求。
